Clinical Trials

TITLE: Effects of Plasma Exchange with Human Serum Albumin 5% (PE-A 5%) on Short term Survival in Subjects with "Acute-On- Chronic Liver Failure" (ACLF) at High Risk of Hospital Mortality

SPONSOR: Grifols Therapeutics LLC

Primary Investigator: Dr. Reddy

CONTACT:  Grace Kim-Lee  GraceKim.Lee@pennmedicine.upenn.edu

Criteria

Inclusion Criteria:

• Male or female cirrhotic subjects between 18 and 79 years of age
• Subjects with ACLF-1b, ACLF-2, or ACLF-3a detected either at admission or during hospitalization (must be ACLF-1b, -2, or -3a within the Screening Period [a maximum of 10 days]).
• Willing and able to provide written informed consent or have an authorized representative able to provide written informed consent on behalf of the subject in accordance with local law and institutional policy.
• In case of HE, informed consent will be provided by a relative or a legally authorized representative (surrogate).

Exclusion Criteria:

• Subjects without ACLF.
• Subjects with ACLF-1a or ACLF-3b (See Table 2-1 for ACLF grades) after the Screening Period.
• Subjects fulfilling inclusion criteria that improve to no ACLF or to ACLF-1a or worsen to ACLF-3b during the Screening Period (between initial evaluation and time of randomization).
• Subjects with ACLF for more than 10 days prior to randomization.
• Subjects with acute or subacute liver failure without underlying cirrhosis.
• Subjects with septic shock requiring use of norepinephrine (> 0.3 mcg/kg/min) or need for a second vasopressor (including terlipressin).
• Subjects with active bacterial or fungal infection: who have received less than 24h of appropriate antibiotic treatment.
• Subjects with severe respiratory failure with PaO2/FiO2 ≤200.
• Subjects with active or recent bleeding (unless controlled for >48 hours).
• Subjects with severe thrombocytopenia (≤20×109/L) (based on local laboratory assessment).
• Subjects with chronic renal failure and currently receiving hemodialysis.
• Evidence of current locally advanced or metastatic malignancy. Subjects with hepatocellular carcinoma within the Milan criteria (1 nodule ≤5 cm or 3 nodules ≤3 cm [Appendix 5]), non-melanocytic skin cancer, and controlled breast or prostate cancer, can be included).
• Subjects with severe chronic heart failure (New York Heart Association [NYHA] class III or IV).
• Subjects with severe pulmonary disease (Global Obstructive Lung Disease [GOLD] stage III or IV).
• Subjects with severe myopathy as defined clinically.
• Subjects with a known infection with human immunodeficiency virus (HIV) or have clinical signs and symptoms consistent with current HIV infection.
• Females who are pregnant, breastfeeding, or if of childbearing potential, unwilling to practice a highly effective method of contraception.
• Subjects with previous liver transplantation.
• Subjects receiving anti-platelet or anti-coagulant therapy (LMWH for DVT prophylaxis is allowed).
• Participation in another clinical study within at least 30 days prior to screening.
• Subjects with active drug addiction (exceptions: active alcoholism or marijuana).
• Subjects with a do-not-resuscitate order.
• In the opinion of the investigator, the subject may have compliance problems with the protocol and the procedures of the protocol.
• Subjects with current infection of COVID19, those who are less than 14 days post recovery or those who have clinical signs and symptoms consistent with COVID19 infection.

TITLE: Prevention of Mortality with Long-Term Administration of Human Albumin in Subjects with Decompensated Cirrhosis and Ascites

SPONSOR: Grifols Therapeutics LLC

Primary Investigator: Dr. Reddy

CONTACT:  Grace Kim-Lee ( GraceKim.Lee@pennmedicine.upenn.edu)

Criteria

Inclusion Criteria:

• Male or female subject ≥18 years of age.
• Subjects with diagnosis of liver cirrhosis (based on clinical, laboratory, endoscopic, and ultrasonographic features or on histology).
• Subjects who have been hospitalized for acute decompensation of liver cirrhosis with ascites (or with prior history of ascites requiring diuretic therapy) with or without ACLF at admission or during hospitalization but without ACLF at Screening.
• In subjects with cirrhosis due to hepatitis B virus, decompensation must occur in the setting of continuous (no less than 3 months) appropriate antiviral therapy.
• In subjects with cirrhosis due to hepatitis C virus, only decompensated patients who will not receive antiviral therapy during the study period will be included (Subjects receiving antiviral therapy within 14 days prior to enrollment cannot be included in the study).
• In subjects with cirrhosis due to autoimmune hepatitis, decompensation must occur in the setting of continuous immunosuppressive therapy.
• Subjects must be willing and able to provide written informed consent or have an authorized representative able to provide written informed consent on behalf of the subject in accordance with local law and institutional policy.
• CLIF-C AD score > 50 points at screening.

Exclusion Criteria:

• Subjects with ACLF at Screening
• Subjects with type 1 HRS currently on treatment with vasoconstrictors or hemodialysis.
• Subjects with TIPS or other surgical porto-caval shunts.
• Subjects with refractory ascites as defined by ICA criteria without any other event of acute decompensation.
• Subjects receiving dual anti-platelet therapy or anti-coagulant therapy (exception: DVT prophylaxis).
• Subjects with ongoing endoscopic eradication of esophageal varices with ≤ 2 endoscopic sessions completed before screening.
• Subjects with evidence of current locally advanced or metastatic malignancy.
• Subjects with acute or chronic heart failure (New York Heart Association [NYHA]).
• Subjects with severe (grade III or IV) pulmonary disease (Global Obstructive Lung Disease [GOLD]).
• Subjects with nephropathy with renal failure with serum creatinine >2 mg/dL or systemic hypertension.
• Subjects with severe psychiatric disorders.
• Subjects with a known infection with human immunodeficiency virus (HIV) or have clinical signs and symptoms consistent with current HIV infection.
• Females who are pregnant, breastfeeding, or if of childbearing potential, unwilling to practice effective methods of contraception
• Subjects with previous liver transplantation.
• Subjects with known or suspected hypersensitivity to albumin.
• Subjects participating in another clinical study within 3 months prior to screening.
• Subjects with active drug addiction (exceptions: active alcoholism or marijuana).
• In the opinion of the investigator, the subject may have compliance problems with the protocol and the procedures of the protocol.
• Subjects with ongoing or recent variceal bleeding (subjects can be included 2 weeks after hemorrhagic episode).
• Subjects with septic shock at screening.
• Subjects with ongoing SBP infection (subjects can be included upon resolution).
• Subjects with current infection of COVID19, those who are less than 14 days post recovery, or those who have clinical signs and symptoms consistent with COVID19 infection.

Trial Contacts

Primary Investigator: Bryson Katona, MD, PhD
Research Coordinator: Jordan Heiman
Email: Jordan.Heiman@pennmedicine.upenn.edu
Telephone: 215-360-0905

Studies

Screening for Pancreatic Cancer in patients with BRCA1/2 Mutations

The study is a prospective, observational, case-control study evaluating the utility of endoscopic ultrasound for the identification of preneoplastic and neoplastic pancreatic lesions in patients at high risk for pancreatic cancer, specifically those with BRCA1/2 mutations.

Title Name: EDHCC – Early Detection and Prognosis of Hepatocellular Carcinoma/Observational

Primary Investigator: Dr. Reddy

Contact: Isabella Pabon (Isabella.Pabon@pennmedicine.upenn.edu)

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Trail Name: CIRRHOSIS

Primary Investigator: EDHCC – Reddy: Early Detection and Prognosis of Hepatocellular Carcinoma/Observational

Contact: Isabella Pabon (Isabella.Pabon@pennmedicine.upenn.edu)

Trial Contacts

Endocytoscopy Primary Investigator: Anna Buchner, MD
Research Coordinator: Julie Starr
jstarr@pennmedicine.upenn.edu

Epi proColon Primary Investigator: Bryson Katona, MD, PhD
Research Coordinator: Justine Jou
Justine.Jou@pennmedicine.upenn.edu
215-360-0833

Research Coordinator: Alice Alderson
Alice.Alderson@pennmedicine.upenn.edu
215-360-0905

Studies

The Role of in Vivo Real Time Endocytoscopy in Diagnosing Colorectal Neoplasia

Endocytoscopy and Colorectal Neoplasia

This is a pilot study to evaluate the role of endocytoscopy in classifying colorectal polyps in vivo. The primary outcomes are to determine the key endocytoscopy image features of neoplastic and non-neoplastic colorectal polyps. The target population includes adult subjects undergoing screening and surveillance colonoscopies.

Epi proColon

Clinical Sample Protocol for Plasma-based Colorectal Cancer Screening Research & Development

Epigenomics has developed Epi proColon, a blood based screening test for colorectal cancer that has been approved by the U.S. Food and Drug Administration (FDA). In this study we are testing investigational colorectal cancer markers and methods to make improvements to the approved test, and to develop other investigational tests. While the Epi proColon test is approved the FDA, the investigational markers, methods and additional tests are not.

Study is recruiting subjects with newly diagnosed colorectal cancer as well as patients undergoing a screening endoscopy.

Participation in the study will require researchers to collect your basic information and a blood sample.

Criteria

Inclusion Criteria: Colorectal Cancer
Willing and able to sign an Informed Consent and adhere to study requirements.
Subjects with colorectal cancer preferably detected by screening (any guideline recommended modality)
Colonoscopy diagnosis of colorectal cancer (CRC)
Blood sampling a minimum of seven days after surgery of CRC and be accompanied by a complete final pathology report.

Inclusion Criteria: Screening Colonoscopy
Willing and able to sign an Informed Consent and adhere to study requirements
Eligible for colorectal cancer screening colonoscopy
45-84 years of age at blood sampling
Able to provide blood sample within up to two weeks prior to bowel prep and colonoscopy

Exclusion Criteria: Colorectal Cancer
Subject with curative biopsy during colonoscopy
Current neoadjuvant treatment
Current diagnosis of any cancer other than CRC, except non-melanoma skin cancer
Known infection with HIV, HBV, or HCV

Exclusion Criteria: Screening Colonoscopy
Previous personal history of CRC, adenomatous polyps>10mm or sessile serrated adenomas
Familial risk for colorectal cancer (one or more 1^stdegree relatives with CRC; known HNPCC or FAP)
History of inflammatory bowel disease
Current neoadjuvant treatment
Current diagnosis of any cancer other than CRC, except non-melanoma skin cancer
Infection with HIV, HBV, or HCV

TITLE: A Phase 2, Randomized, Double-Blind, Multi-Center Study in Adult Subjects with Eosinophilic Esophagitis (EoE) to Evaluate the Safety and Efficacy of Vonoprazan 20 mg Compared to Placebo After 12 Weeks and to Evaluate the Safety and Efficacy of Vonoprazan 20 mg Up to 24 Weeks

SPONSOR: Phathom Pharmaceuticals, Inc.

Primary Investigator: Kristle Lynch, MD

CONTACT: Maureen DeMarshall, BSN, RN (demarshm@pennmedicine.upenn.edu or 215-349-8546)

• A Phase 2 study to investigate the use of Vonoprazan as a treatment for EOE
• 12 weeks 1:1 (20mg or placebo daily) followed by 12 weeks OLE (20mg)

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TITLE: Double-blind, double-dummy, randomized, parallel-group, non-inferiority phase III trial on the efficacy and tolerability of 2 mg once daily vs. 1 mg twice daily budesonide orodispersible tablets for induction of histological remission in adults with eosinophilic esophagitis

SPONSOR: Dr. Falk Pharma.

Primary Investigator: Gary W. Falk, MD

CONTACT: Maureen DeMarshall, BSN, RN (demarshm@pennmedicine.upenn.edu or 215-349-8546)

• EOS-4: Phase 3 trial on the efficacy and tolerability of 2mg daily vs. 1mg twice daily of budesonide orodispersible tablets
• 6 weeks 1:1 (2mg daily or 1mg twice daily)

Title: Eosinophilic Gastritis Gastroenteritis

HUDSON: A Multi-center, Randomized, Double-blind, Parallel-group, Placebo-controlled 3-Part Phase 3 Study to Demonstrate the Efficacy and Safety of Benralizumab in Patients with Eosinophilic Gastritis and/or Gastroenteritis

Primary Investigator: Kristle Lynch, MD

CONTACT: Maureen DeMarshall, BSN, RN (demarshm@pennmedicine.upenn.edu or 215-349-8546)

Inclusion:

• Clinician confirmed diagnosis of EG/EGE for at least 3 months prior to screening.
• Participants who have documented previous diagnosis of eosinophilic gastritis, with or without duodenitis, or eosinophilic duodenitis alone. This will be confirmed by biopsy for the purpose of this study, defined as a gastric count of ≥30 eosinophils/hpf in at least 5 hpfs and and/or duodenal eosinophil count ≥30 eosinophils/hpf in at least 3 hpfs without any other cause for the gastrointestinal eosinophilia (eg, parasitic or other infection or malignancy). Participants can have duodenal only disease and be enrolled in the duodenal only subject population. See Section 8.1.1 for details regarding endoscopy and biopsy.
• At Visit 1 (screening), participants who in the investigator’s judgement have a history symptoms of abdominal pain, nausea, bloating, early satiety, and/or loss of appetite to an extent that they would meet criteria 5 at Visit 2.

Exclusion:

• Other gastrointestinal disorders such as active Helicobacter pylori infection, history of achalasia, esophageal varices, Crohn's disease, ulcerative colitis, inflammatory bowel disease, or celiac disease
• Hypereosinophilic syndrome or eosinophilic granulomatosis with polyangiitis.
• Helminth parasitic infection diagnosed within 24 weeks

Trial Contacts

Primary Investigator: Bryson Katona, MD, PhD
Research Coordinator: Julie Starr
jstarr@mail.med.upenn.edu
215-349-8527

Studies

Title: A Phase 1b-2, Multicenter, Trial To Evaluate The Efficacy, Safety, Pharmacokintetics, And Pharmacodynamics Of REC-4881 in Patients With Familial Adenomatous Polyposis (FAP)

Sponsor: Recursion Pharmaceuticals Inc.
Primary Investigator: Bryson Katona, MD, PhD
CONTACT: Julie Starr (Julie.Starr@pennmedicine.upenn.edu or 215-349-8527)

Inclusion Criteria:

• Male or female and ≥ 55 years of age
• Have provided written informed consent to participate in the study
• Diagnosis of phenotypic classical FAP with disease involvement of the duodenum or the residual colon/rectum/pouch as the primary disease site
• Genetic diagnosis of FAP with APC gene mutation
• Has undergone colectomy or subtotal colectomy
• No significant cardiovascular abnormalities
• Left ventricular ejection fraction of >50% as determined by echocardiogram
• No significant hematopoietic abnormalities
• No significant hepatic abnormalities
• No significant renal abnormalities

Exclusion Criteria:

• No clinically significant laboratory abnormality, medical or psychiatric illness
• Has had prior pelvic irradiation
• Has gastrointestinal disease or recent gastrointestinal procedure that could interfere with oral absorption of REC-4881
• Has received treatment with other investigational agents prior to Study Day 1
• Treatment with other FAP-directed drug therapy within 8 weeks of screening endoscopy (Part 2 only)
• Is currently under treatment for desmoid tumors
• Use of omega-3 fatty acids or oral corticosteroids prior to Study Day 1
• Use of strong CYP3A inhibitors or inducers prior to Study Day 1
• History of an ongoing or newly diagnosed eye abnormality
• Cancer at screening endoscopy in GI tract (including stomach, duodenum, and colon/rectum/pouch) (Part 2 only)
• Has a large polyp (>1 cm) not amenable to complete removal
• Has active pancreatitis secondary to pancreatic duct obstruction
• Has active gall bladder disease
• Is pregnant, lactating or is planning to attempt to become pregnant during the study

Studies

CAPS-5 Study (The Cancer of the Pancreas Screening-5) 

The Cancer of the Pancreas Screening-5 (CAPS5) Study

• Aim 1: To evaluate pancreatic fluid mutations and circulating pancreatic epithelial cells as accurate markers of neoplasia by comparing their prevalence in cases with sporadic pancreatic neoplasia to healthy and disease controls.
• Aim 2: To compare the prevalence of pancreatic fluid mutations and circulating pancreatic epithelial cells among a prospective cohort of individuals with sporadic pancreatic cysts undergoing pancreatic surveillance.
• Aim 3: To determine the prevalence of pancreatic lesions, pancreatic fluid mutations and circulating pancreatic epithelial cells among a large cohort of high-risk individuals undergoing pancreatic screening and surveillance of a new cohort in which screening is begun at age >55.

Criteria for clinical trial

See Screening for Pancreatic Cancer in patients with BRCA1/2 Mutations

A prospective, multi-center investigational study of IMMray™ PanCan-d diagnostic platform for early detection of pancreatic ductal adenocarcinoma in high-risk populations (PANFAM-1)

Inclusion criteria:

1. Individuals (both male and female) with the following family phenotype and age will be included in the study:
• Two or more first-degree relatives (FDR) ; ≥50 years OR 10 years before onset in family
• Three or more relatives with at least 1 FDR and 2 second degree relatives (SDR) ; ≥50 years OR 10 years before onset
• Any of (BRCA1, BRCA2, PALB2, ATM) mutations + 1 FDR or SDR with PDAC ; ≥50 years OR 10 years before onset
• FAMMM (p16,CDKN2A mutations); ≥50 years OR 10 years before onset
• Known mutation carrier for STK11 (Peutz Jeghers Syndrome); ≥35 years
• Lynch syndrome (HNPCC) + 1 FDR or SDR with PDAC; ≥50 years OR 10 years before onset
• Known mutation carrier for Hereditary pancreatitis with history of symptomatic pancreatitis ≥50 years OR 10 years before onset

Contact Jordan Heiman at Jordan.Heiman@pennmedicine.upenn.edu

GASTROPARESIS

TITLE: A multicenter, randomized, double-blind, placebo-controlled phase III study to assess the efficacy of tradipitant in relieving symptoms of gastroparesis

SPONSOR: Vanda

Primary Investigator: Nitin Ahuja, MD

CONTACT: Lilly Hennessey Lilly.Hennessey@pennmedicine.upenn.edu

Criteria

Inclusion Criteria:

• Diagnosed with gastroparesis
• Demonstrated delayed gastric emptying
• Presence of moderate to severe nausea
• Body Mass Index (BMI) of ≥18 and ≤40 kg/m2

Exclusion Criteria:

• Another active disorder or treatment which could explain or contribute to symptoms of gastroparesis
• A positive test for drugs of abuse at the screening or evaluation visits;
• Exposure to any investigational medication in the past 60 days
• Gastrectomy, fundoplication, vagotomy, pyloroplasty, bariatric surgery, or gastric stimulation device surgically implanted within the last year

HRS-AKI

TITLE: InFUSE Study - Multi-Center, Open Label, Collaborative Research Study to Treat HRS-AKI Patients with Continuous Terlipressin Infusion

SPONSOR: Penn Medicine

Primary Investigator: Ethan Weinberg, MD, MS

CONTACT: Maggie Harte (Maggie.Harte@Pennmedicine.upenn.edu) 

Inclusion Criteria:

1. Written informed consent by subject or legally authorized representative.
2. At least 18 years of age.
3. Cirrhosis and ascites.
4. No sustained improvement in renal function (less than 20% decrease in SCr) at least 48 hours after diuretic withdrawal and after plasma volume expansion with albumin (given daily for two days - 48 hours minimum from 1st dose). If SCr improves by ≥ 20 % but plateaus ( ≤ 10 % fluctuation in sCr) and remains above 1.5 mg/dl for ≥another 48 hrs and there are no features of acute tubular necrosis.
5. Increase in SCr by at least ≥ 0.3 mg/dl OR 1.5-2 fold above baseline (AKI stage 1 and above), to a SCr of ≥ 1.5 mg/dl at the time of initiating treatment. Baseline SCr is defined as the most recent, lowest SCr within last 6 months before date of current admission.
6. A.On liver transplant wait list or liver transplant eligible with anticipation of being placed on the liver transplant wait list. B. Patients not on the transplant waitlist or transplant eligible are also eligible for the trial ( maximum 25 subjects) -

Exclusion Criteria:

1. Serum creatinine level greater than 5.0 mg/dL. Subjects with value greater than 5.0 mg/dL may be enrolled with Sponsor prior approval.
2. MELD score ≥ 35
3. Acute on Chronic Liver Failure (ACLF) grade 3 (according to the CLIF Consortium grading system).
4. Uncontrolled sepsis and/or uncontrolled bacterial infection (e.g., persisting bacteremia, persisting ascitic fluid leukocytosis, fever, increasing leukocytosis with vasomotor instability).
5. Shock.
6. Current or recent (within 4 weeks) treatment with or exposure to nephrotoxic agents: eg, aminoglycosides, amphotericin, cyclosporine A, cisplatin, nonsteroidal anti-inflammatory drugs (NSAIDs: e.g., ibuprofen, naproxen, diclofenac), significant exposure to radiographic contrast agents (large doses or multiple injections of iodinated contrast media; e.g., during coronary or abdominal angiogram).
7. Estimated life expectancy of less than 7 days.
8. Advanced Hepatocellular Carcinoma ( HCC) with expected survival of < 6 months
9. Superimposed acute liver injury due to drugs (e.g., acetaminophen), dietary supplements, herbal preparations, viral hepatitis, or toxins (e.g., Amanita toxin with mushroom poisoning carbon tetrachloride), with the exception of acute alcoholic hepatitis.
10. Evidence of obstructive uropathy or parenchymal renal disease. Renal ultrasound or other imaging not required but should be taken if suspicious.
11. Tubular epithelial casts, heme granular casts (range of 1-3 granular casts acceptable), hematuria or microhematuria on urinalysis that is indicative of acute tubular necrosis and/or intrinsic renal disease.
12. Subjects known to be pregnant; all women of child-bearing age and potential must have a negative pregnancy test.
13. Severe cardiovascular disease, including, but not limited to, unstable angina, pulmonary edema, congestive heart failure, or persisting symptomatic peripheral vascular disease, myocardial infarction or stable chronic angina within the past 12 months, or any other cardiovascular disease judged by the investigator to be severe and creates a risk to subject with concurrent terlipressin use.
14. Current or recent (within 4 weeks) renal replacement therapy (RRT) or anticipation of RRT within 3 days on enrollment.
15. Participation in other clinical research involving investigational medicinal products within 30 days of starting study drug that would adversely affect participation in this or the current trial.
16. Transjugular intrahepatic portosystemic shunt (TIPS) within 30 days of starting study drug.
17. For the Prospective Group: All vasopressors must be stopped prior to treatment with terlipressin. Use of vasopressors (e.g., norepinephrine, epinephrine or vasopressin dopamine or other vasopressors) of ≥ 3 consecutive days within the prior 14-day screening period are excluded. Patients receiving a vasopressor other than midodrine within 24 hours of qualifying SCr are excluded, i.e, a 24-h washout is required prior to enrollment. Note: Patients receiving midodrine and octreotide may be enrolled. Midodrine and octreotide treatment must be stopped prior to enrollment.
18. Known allergy or sensitivity to terlipressin.

Trial Contacts

I3 - Research Coordinator: 215-360-0904
I3Study@uphs.upenn.edu
www.i3study.org

PIANO - Research Coordinator: TBD
215-662-8919

Target-IBD
Primary Investigator: Faten Aberra, MD, MSCE
Research Coordinator: Alice Alderson
Alice.Alderson@pennmedicine.upenn.edu
215-360-0905

Studies

PIANO

Inflammatory Bowel Disease and Neonatal Outcomes

I3: IBD Immunology Initiative

A translational clinical and tissue database study.

Actively enrolling all Crohn's disease and Ulcerative Colitis patients seen within the University of Pennsylvania Health System.  The aim is to understand abnormalities in the immune system and other factors that impact IBD.

IBD faculty

Faten Aberra, MD, MSCE
Faten Aberra is an Assistant Professor of Medicine at the University of Pennsylvania Perelman School of Medicine. She serves as the Co-Director for the Inflammatory Bowel Disease Center Joint-CHOP-Penn Center for Digestive, Liver and Pancreatic Medicine. Dr. Aberra serves on the National Scientific Advisory Committee for the Crohn’s Colitis Foundation of America (CCFA) and co-chair of the Patient Education Committee for the CCFA. Her clinical research interests are in inflammatory bowel disease and gastrointestinal infections. Her research in IBD involves understanding triggers for IBD disease activity, optimizing medical care of IBD patients and medical therapy clinical trials. Dr. Aberra has served at the primary investigator at Penn for several pharmaceutical industry therapy trials over the past decade, most recently UNITI and IMUNITI trials (Phase III clinical trials assessing ustekinumab for Crohn’s disease) and RBX2660 (microbiota suspension) for recurrent Clostridium difficile infection. Dr. Aberra has been elected to Best Doctors and has received the Castle Connolly Top Regional Doctor Award. She sees patients with inflammatory bowel disease at Perelman Center for Advanced Medicine.

Meenakshi Bewtra, MD MPH PhD
Meenakshi Bewtra is an Assistant Professor of Medicine and Epidemiology at the University of Pennsylvania Perelman School of Medicine and a Senior Scholar in the Center for Clinical Epidemiology and Biostatistics at the University of Pennsylvania. Dr. Bewtra sees patients with inflammatory bowel disease at the Perelman Center for Advanced Medicine. Dr. Bewtra has also been conducting clinical research for nearly 10 years in inflammatory bowel disease with a focus on natural history of inflammatory bowel disease, outcomes of disease and medication safety using observational data and statistical modeling, measures of risk and risk tolerance for therapies using discrete choice experiment, and clinical trials for educational interventions and novel therapies. Dr. Bewtra is also the PI of the IBD-Immunology Initiative (I3), a prospective clinical and tissue biobank actively enrolling all inflammatory bowel disease patients seen at the University of Pennsylvania. The I3 has collaborators within the University of Pennsylvania, nationally and internationally in both academia and industry and is participating in several studies examining the basic mechanisms of IBD and predictors of response to therapies with the goal of improving personalized medicine in inflammatory bowel disease. Dr. Bewtra’s work has been funded by the NIH, CCFA, AGA, PCORI, pharmaceutical industries, and private philanthropy. She is currently a member of the Crohn’s and Colitis Foundation of America, the American Gastroenterology Association and the American College of Gastroenterology.

Anna Buchner, MD PhD
Anna Buchner is an Assistant Profess of Medicine at the University of Pennsylvania Perelman School of Medicine. She sees patients with inflammatory bowel disease at the Perelman Center for Advanced Medicine and Penn Medicine at Radnor. Dr. Buchner’s research focuses on the application of advanced imaging technologies, for the detection and treatment of early cancers and pre-cancerous lesions of the gastrointestinal tract including dysplastic colonic lesions in patients with long standing IBD. She specifically utilizes various imaging technologies such as virtual chromoendoscopy (NBI), traditional chromoendoscopy (with methylene blue or indigo carmine) and confocal microscopy (probe based confocal endomicroscopy pCLE) to detect and characterize such lesions, guide their endoscopic resection and post endoscopic mucosal resection (EMR) follow up as well as to assess the disease activity. Currently, Dr. Buchner is conducting a prospective cohort study evaluating the utility of confocal endomicroscopy in diagnosing colorectal neoplasia in patients with longstanding IBD undergoing surveillance colonoscopy with chromoendoscopy. 

James Lewis, MD MSCE
James Lewis is Professor of Medicine and Epidemiology and Senior Scholar in the Center for Clinical Epidemiology and Biostatistics at the University of Pennsylvania’s Perelman School of Medicine in Philadelphia, Pennsylvania. Dr. Lewis serves as the Associate Director of the Penn Inflammatory Bowel Disease Center. He has been actively involved in clinical research related to inflammatory bowel diseases, medication safety, and optimizing medical therapies for more than 15 years. During the last 5 years, he has additionally focused on the impact of diet on the gut microbiome and the course of inflammatory bowel disease. He has employed a various research methods to address these questions, ranging from mathematical modeling to placebo controlled randomized trials. His work has been funded by the NIH, AHRQ, PCORI, and numerous foundations and corporate sponsors. Dr. Lewis previously served as the Chair of the National Scientific Advisory Committee for the Crohn’s & Colitis Foundation of America (CCFA) and as associate editor for Gastroenterology and Pharmacoepidemiology and Drug Safety. He is currently the lead scientist for the CCFA’s IBD Plexus.

Gary Lichtenstein, MD
Gary Lichtenstein is the Director of the Inflammatory Bowel Disease Center and a Professor of Medicine at the University of Pennsylvania School of Medicine. He sees patients with inflammatory bowel disease at the Perelman Center for Advanced Medicine. Dr. Lichtenstein has received numerous awards, including the Scientific Achievement from the national Crohn’s and Colitis Foundation of America for his clinical work and research, the Louis A. Duhring Award for the top specialist in the University of Pennsylvania Health system, the Christina and Marie Lindback teaching award, and many others. He is annually listed in “The Best Doctors in America” in Philadelphia Magazine. An invited lecturer at the local, national, and international levels, Dr. Lichtenstein is the author or coauthor of more than 325 peer-reviewed primary articles and chapters, and he has presented over 250 abstracts and edited 18 books. He has lectured at a national and an international level at over 500 invited conferences, lectures, symposia, and institutional grand rounds. His current research interests encompass investigational therapies for the treatment of ulcerative colitis and Crohn’s disease as well his research has had a significant focus on the safety of current and future medical therapy, including thiopurines, anti-TNF therapy, and anti-integrin therapy, both overall and also in the elderly and in pregnant patients. He has also focused his research on the natural history of disease as well as investigating factors predictive of unplanned hospital readmission. In particular he has evaluated factors predicting patient response to therapies with a special focus on biologic therapies. Dr. Lichtenstein has received numerous research grants focusing on these areas and has served as the national/international principal investigator evaluating novel agents for therapeutic trials in the treatment of ulcerative colitis and Crohn’s disease. He is leading a multitude of prospective clinical studies currently, including assessment of factors predicting response to anti-TNF therapy, safety of long-term mesalamine maintenance, factors predicting the disease course in patients with IBD, chromoendoscopy in IBD, and endoscopic endpoints in patients with IBD.

Farzana Rashid, MD
Dr. Rashid is an Assistant Professor of Clinical Medicine at the University of Pennsylvania Perelman School of Medicine. She sees patients at Penn Presbyterian Medical Center and Penn Medicine at Radnor. Dr. Rashid's clinical practice includes patients with inflammatory bowel disease and she has a specific interest in helping adolescents and young adults transition to adult gastroenterology care. Dr. Rashid is a board member of the CCFA Philadelphia Chapter in addition to being on the Chapter Medical Advisory Committee. She has recently served on the CCFA National Patient Education Committee as well. Dr. Rashid is very involved in medical education for medical students, internal medicine residents, and gastroenterology fellows with a focus on teaching medical students through lectures, courses, and clinical rotations. She also teaches urogynecology fellows through lectures and clinical rotations and surgery residents and colorectal surgery fellows in their yearly core curriculum lecture on the Medical Management of IBD. She has been an investigator in various clinical trials at Penn Presbyterian Medical Center.

Katherine Weyant, CRNP
Kate Weyant specializes in Inflammatory Bowel Diseases (IBD). She holds a Master’s degree as a Family Nurse Practitioner from Pennsylvania State University. Kate joined the Division of Gastroenterology at University of Pittsburgh where she worked with internationally recognized experts in IBD. She divided her time between clinical care and clinical/translational research, which led to publication, and national conference participation. She developed a particular interest in nutrition and coordinated inpatient nutritional services for patients with complex gastrointestinal failure. Kate sees patients with inflammatory bowel disease at Penn Presbyterian Medical Center.

Gary Wu, MD
Gary Wu is the Ferdinand G. Weisbrod Professor of Medicine at the University of Pennsylvania Perelman School of Medicine. He serves as the Associate Chief for Research in the Division of Gastroenterology, Co-Director of the Penn-CHOP Microbiome Program, Associate Director of the Joint Penn-CHOP Center for Digestive, Liver and Pancreatic Medicine, and the Associate Director of the Center for Molecular Studies in Digestive and Liver Disease in which he is the Director of its Molecular Biology Core. He is an elected member of both the American Society for Clinical Investigation and the Association of American Physicians. Dr. Wu has held many leadership positions nationally including the Chair of the NIH NIDDK-C Study Section, Co-Senior Associate Editor for Gastroenterology, Chair of the Intestinal Disorders Sections and member of the AGA Council. He is currently Director and Chair of the Scientific Advisory Board for the American Gastroenterological Association Center for Gut Microbiome Research and Education. He is the past Grants Council Chair and current Chair of the Research Initiatives Committee for the Crohn’s and Colitis Foundation of America. Research in the Wu lab is focused on the interaction between diet, the gut microbiome, and host metabolome. He has gained national recognition for his highly innovative and translational avenues of investigation that will help to guide the development of therapeutic strategies relevant to IBD and metabolic diseases. Dr. Wu will be Principal Investigator for 2 clinical trials in 2016: 1) "Food and Resulting Microbial Metabolites (FARMM)," a human intervention study designed to characterize the dietary-dependent contribution of the gut microbiome to the human plasma metabolome, which is funded by the CCFA; and 2) "Ileostomy Diet Study on the Gut Microbiome and its Metabolome," a human intervention study designed to characterize the gut microbiome and metabolome of patients with ileostomies, which is funded by the CCFA/Broad Medical Foundation.

Title: Study of the Research Medicine CIN-103 in Adults With Irritable Bowel Syndrome With Predominant Diarrhea (IBS-D)

Sponsor: CinPhloro
Primary Investigator: Nitin Ahuja, MD
CONTACT: Sophia Caterina (Sophia.Caterina@pennmedicine.upenn.edu or 215-349-8545)

Inclusion Criteria:

• Are adult male and female subjects ≥ 18 years of age
• Have a body mass index between 18 and 40 kg/m2, inclusive at Screening
• Meet Rome IV Criteria for IBS-D by subject self-report of recurrent abdominal pain that is associated with ≥ 2 of the following over the last ≥ 6 months, with frequency of at least 1 day per week over the last 3 months (on average) before enrollment:
  •  Related to defecation;
  • Associated with a change in frequency of stool; and/or
  • Associated with a change in form (appearance of stool)
• Based on Investigator interview of subject's symptoms over the last 3 months, have ≥ 25% of bowel movements (BMs) with Bristol Stool Scale (BSS) types 6 or 7 (loose or watery stools) and < 25% of BMs with BSS Type 1 or 2 (lumpy or hard stools) per the Rome IV Criteria for IBS-D
• In the opinion of the Investigator, are on a stable diet for ≥ 4 weeks prior to Screening and are not planning to change lifestyle, exercise, and/or diet that may impact symptoms of IBS-D during study participation
• Have a fecal calprotectin < 50 mcg/g at the Screening Visit or Visit 2
• Have a serum tTG-IgA (tissue transglutaminase immunoglobulin A) ≤ 3 U/mL at the Screening Visit
• Have undergone a colonoscopy examination within the designated time interval prior to randomization, if they meet any of the following criteria:
  • Average risk, based on US Preventive Services Task Force Recommendation Statement for screening of colorectal cancer, with age ≥ 45 years (colonoscopy within 10 years)
  • Personal history of completely removed adenomatous colorectal polyps (colonoscopy within 5 years for polyps >1 cm, within 10 years for polyps <1 cm)
  • History of colorectal cancer or adenomatous polyps in a first-degree relative before age 60 (colonoscopy within 5 years)History of colorectal cancer or adenomatous polyps in ≥ 2 first-degree relatives at any age, or family history of hereditary colorectal cancer or polyposis (colonoscopy within 5 years); or
  • History of or active inflammatory bowel disease in first-degree relative (colonoscopy any time)

Exclusion Criteria:

• Have a diagnosis or suspected diagnosis of IBS with a subtype of constipation, IBS with mixed or alternating bowel habits, un-subtyped IBS, or functional constipation by the Rome IV Criteria
• Have a history of or current inflammatory bowel disease (ie, Crohn's disease, ulcerative colitis, indeterminate colitis), microscopic colitis, lymphocytic colitis, celiac disease, non-celiac gluten sensitivity and non-compliant on a gluten-free diet, untreated lactose intolerance, carcinoid syndrome, Lynch syndrome, or familial polyposis
  • Note: Lactose intolerance and non-celiac gluten sensitivity will not exclude a subject from participation if the Investigator documents that the subject is compliant on a special diet (lactose-free diet or gluten-free diet, respectively) and/or for lactose intolerance is successfully treated with commercial lactase supplement(s)
• Have a known history of a pelvic floor disorder (unless successful treatment has been documented by a normal balloon expulsion test), refractory constipation not responsive to standard medical therapy, fecal impaction that required hospitalization, cathartic colon, and/or active proctological condition
• Have a history of or current non-IBS chronic condition(s) with ongoing symptoms associated with abdominal pain or GI discomfort (eg, gastroparesis, functional dyspepsia, uncontrolled gastroesophageal reflux disease, polycystic kidney disease, ovarian cysts, urological pain, or endometriosis)
• Have a history of or current clinically significant arrhythmias as judged by the Investigator, including ventricular tachycardia, ventricular fibrillation, and Torsades de pointes. Subjects with any abnormal electrocardiogram (ECG) not considered clinically significant by the Investigator are not necessarily excluded
• Have current or a history of diverticulitis, heme positive stool, or unexplained GI bleeding within 3 months prior to Screening
  • Note: Surgically repaired diverticulitis > 3 months prior to Screening is permitted
• Have a history of surgical resection of the stomach, small, or large intestine

NASH

TITLE: Research Study on Whether Semaglutide Works in People with Non-alcoholic Steatohepatitis (NASH)

SPONSOR: Novo Nordisk

Primary Investigator: Ethan Weinberg, MD, MS

CONTACT: Aimee Stonelake ( Aimee.Stonelake@pennmedicine.upenn.edu ) 

Inclusion Criteria:

• Age above or equal to 18 years at the time of signing informed consent.
• Histological evidence of NASH based on a central pathologist evaluation of the baseline liver biopsy. The baseline liver biopsy can be a historical biopsy obtained within 180 days prior to the screening visit (V1).
• Histological evidence of fibrosis stage 2 or stage 3 according to the NASH CRN (Clinical Research Network) classification based on a central pathologist evaluation of the baseline liver biopsy.
• A histological NAS (Non-alcoholic fatty liver disease Activity Score) above or equal to 4 with a score of 1 or more in both steatosis, lobular inflammation and hepatocyte ballooning based on a central pathologist evaluation of the baseline liver biopsy.

Exclusion Criteria:

• Documented causes of chronic liver disease other than non-alcoholic fatty liver disease (NAFLD)
• Positive HBsAg, positive anti-HIV, positive HCV RNA at screening (V2A) or any known presence of HCV RNA or HBsAg within 2 years of screening (V2A).
• Presence or history of ascites, variceal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis or liver transplantation at randomisation.
• Known or suspected excessive consumption of alcohol (greater than 20 g/day for women or greater than 30 g/day for men) or alcohol dependence (assessed by the Alcohol Use Disorders Identification Test (AUDIT questionnaire)).
• Treatment with vitamin E (at doses greater than or equal to 800 IU/day) or pioglitazone or medications approved for treatment of NASH which has not been at a stable dose in the period from 90 days prior to the screening visit (V2A). In addition, for subjects with historical liver biopsies taken more than 90 days prior to screening, treatment should be at a stable dose in from time of biopsy until screening.
• Treatment with GLP-1 RAs in the period from 90 days prior to the screening visit (V2A). In addition, for subjects with historical liver biopsies taken more than 90 days prior to screening, any treatment with GLP-1 RAs from time of biopsy until screening (V2A).
• Treatment with glucose-lowering agent(s) (other than GLP-1 RAs), lipid-lowering medication or weight loss medication not stable in the opinion of the investigator in the period from 90 days prior to the screening visit (V2A). In addition, for subjects with historical liver biopsies taken more than 90 days prior to screening, treatment should be at a stable dose in the opinion of the investigator from time of biopsy until screening.

TITLE: Alfapump® system in the treatment of refractory or recurrent ascites: a multicenter single arm non-randomized within subject crossover design pivotal study

SPONSOR: Sequana Medical

Primary Investigator: K. Rajender (Raj) Reddy, MD

CONTACT: Maggie Harte (Maggie.Harte@Pennmedicine.upenn.edu)

TITLE: A Phase 2 Randomized, Controlled, Dose-titration, Open-Label Study Evaluating the Safety and Efficacy of BIV201 in Addition to Standard of Care Compared to Standard of Care to Reduce the Recurrence of Ascites and Complications in Patients with Refractory Ascites Secondary to Decompensated Liver Cirrhosis

SPONSOR: Biovie Inc.

Primary Investigator: K. Rajender (Raj) Reddy, MD

CONTACT: Grace Kim-Lee (GraceKim.Lee@pennmedicine.upenn.edu) 

Inclusion Criteria

• Informed consent prior to any study-related procedures
• Male or female patients age 18 to 75 years old
• Cirrhosis of the liver (Non-alcoholic steatohepatitis, alcohol, viral and autoimmune)
• Patient has diuretic-resistant, intractable ascites or is unsuitable for treatment with diuretics and required:
  • In the 60-day period from the last LVP before consent, required, between 3 and 9 LVPs, including the last LVP on or before the day of consent.
• Dates for all LVPs that occurred within 90 days prior to consent have been recorded. The volume of ascites removed at each of the LVPs must also have been recorded for the 90-day period prior to the last LVPs before consent
• Serum creatinine (SCr) ≤2.00 mg/dL determined prior to randomization
• Women of child-bearing potential (e.g. not post-menopausal for at least one year or surgically sterile) must be neither pregnant nor lactating and must agree to use adequate birth control or be abstinent for the duration of the study
• If patient is treated with ACE inhibitors or beta blockers, dose has been stable for at least 30 days prior to randomization and may be maintained on that dose for the trial duration
• If patient is treated with diuretics, patient has been on a stable daily dose for at least 10 days prior to consent
• Willing and able to comply with trial instructions

Exclusion Criteria

• Ascites with causes other than cirrhosis; such as cardiac or nephrogenic ascites or malignant ascites due to peritoneal carcinomatosis
• Urinary sodium excretion >100 mmol/day between day of consent and randomization
• Total bilirubin >5 mg/dL
• Blood clotting International normalized ratio (INR) >2.5
• Current or recent (within 3 months of consent) renal replacement therapy
• Current or recent (within 3 month of consent) hepatic encephalopathy Grade 3 or 4 (West-Haven)
• Superimposed acute liver failure/injury due to factors including acute alcoholic hepatitis, acute viral hepatitis, drugs, medications (e.g., acetaminophen), or other toxins (e.g., mushroom [Amanita] poisoning)
• History or presence of hepatic hydrothorax, known pulmonary hypertension and a history of hepatopulmonary syndrome
• Current or recent treatment (within 7 days of randomization) with octreotide, midodrine, vasopressin, dopamine or other vasopressors
• Current or recent (in the previous 60 days from consent) episode of respiratory failure requiring positive airway pressure (PAP) devices or intubation
• Sepsis episode in the previous 28 days from consent
• Episode of SBP within the 28 days prior to consent
• Episode of gastrointestinal hemorrhage (non-variceal) within 28 days prior to consent
• Episode of esophageal variceal bleed within one week prior to consent
• Ongoing documented or suspected infection
• Severe cardiovascular disease that is a contraindication to terlipressin therapy such as a history of myocardial infarction, angina pectoris, advanced arteriosclerosis, uncontrolled cardiac arrhythmia, severe coronary insufficiency or uncontrolled hypertension
• Findings suggestive of severe organic renal disease (severe proteinuria/hematuria, or abnormal renal ultrasound suggestive of obstructive renal pathology)
• Use of nephrotoxic drugs (e.g., aminoglycosides) in the 4 weeks before screening
• Severe comorbidity that in the opinion of the Investigator would affect short-term prognosis and/or disallow safe participation in the trial (such as for example, severe anemia or pancytopenia, advanced progressive neoplasia such as hepatocellular carcinoma, unless eligible for transplant)
• Patient who, in the judgment of the investigator, has been an excessive alcohol drinker in the past 12 weeks
• Patient is in the opinion of the investigator, despite previous education on sodium restriction, anticipated to remain grossly non-compliant of sodium restricted diet
• Implanted alfapump or previous recipient of alfapump that had pump removed within past 3 months
• Recipient of renal or liver transplant
• Planned elective surgery related to cirrhosis complications, for example for hernia repair
• Known allergy or hypersensitivity to terlipressin
• Participation in other clinical research studies involving the treatment with other investigational drugs or evaluation with implantable devices within 30 days of consent

Title: Paclitaxel Coated Balloon for the Treatment of Chronic bEnigN sTricture- Esophagus (PATENT-E)

To evaluate the safety and efficacy of the ProTractX3™ DCB for the treatment of benign esophageal strictures.

Sponsor: GIE Medical.
Primary Investigator: Gregory Ginsberg, MD
CONTACT: Christine Gepty (Christine.Gepty@pennmedicine.upenn.edu or 215-349-8556)

Inclusion Criteria:

• Age ≥ 22 years
• Diagnosis of a benign esophageal stricture with at least 2 previous dilations to at least 14mm within the last 12 months
• Target benign esophageal stricture etiologies include:
  • Peptic stricture
  • Schatzki's ring
  • Stricture due to prior infection
  • Post-procedural (e.g. ESD/EMR/RFA/Cryo) stricture
  • Post surgical (e.g. anastomotic), including post curative esophagectomy with or without prior neoadjuvant chemoradiation therapy

Exclusion Criteria:

• Two or more clinically significant (e.g. non-traversable) strictures with total length >5cm or unable to be treated with a single balloon
• Female subjects who are pregnant or breastfeeding or plan to become pregnant in next 12 months
• Contraindication to endoscopy, anesthesia or deep sedation
• Benign esophageal stricture due to extrinsic esophageal compression, caustic ingestion, and purely radiation induced strictures (e.g. post head/neck cancer treatment)
• History of diagnosis of eosinophilic esophagitis (EoE)

Title: Paclitaxel Coated balloon for the Treatment of chronic bEnigN sTricture- Bowel

To determine the safety and efficacy of GIE Medical's ProTractX3™ TTS DCB for the treatment of recurrent benign bowel strictures.

Sponsor: GIE Medical.
Primary Investigator: Gregory Ginsberg, MD
CONTACT: Christine Gepty (Christine.Gepty@pennmedicine.upenn.edu or 215-349-8556)

Inclusion Criteria:

• Age ≥ 22
• Diagnosis of symptomatic benign bowel stricture with at least 2 previous dilations
• Willing and able to complete protocol required follow up
• Willing and able to provide written informed consent
• Stricture length ≤ 5 cm

Exclusion Criteria:

• Female subjects who are pregnant or breastfeeding or plan to get pregnant in next 12 months
• Contraindication to endoscopy, anesthesia, or deep sedation
• Suspicion of malignant bowel stricture NOTE: Biopsy should be taken for every stricture during the initial endoscopy, however endoscopic balloon dilation may proceed without awaiting results if suspicion for malignancy is low in the opinion of the investigator
• Benign stricture due to extrinsic compression
• Stricture is not amenable to standard balloon dilation (e.g. severe angulation, unable to pass guidewire, etc.)
• Stricture complicated with abscess, fistula, deep ulceration, perforation, leakage or varices
• Multiple clinically significant strictures separated by greater than 5 cm
• Received steroid injections into target stricture in the last 4 weeks