CURRENT RESEARCH STUDIES (GI and Hepatology Clinical Research Office University of Wisconsin)

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1 CURRENT RESEARCH STUDIES (GI and Hepatology Clinical Research Office University of Wisconsin) OPEN TO ENROLLMENT: Liver Studies Seroprevalence of Hepatitis E in Organ Transplant subjects PI: Michael Lucey Up to 300 patients who received liver, renal or small bowel transplant from 3 participating transplant centers will be recruited in the study. At least half of the cases will be liver transplant recipients. Enrollment of transplant recipients will be stratified based on number of years posttransplant, one, two and three years and by transplant center. Controls will consist of patients on the waitlist matched for age, waitlist organ and transplant center. After providing written, informed consent, subjects will undergo testing for HEV serology (HEV IgG and IgM) and HEV RNA by RT- PCR. InTeam - Integrated Approaches for Identifying Molecular Targets in Alcoholic Hepatitis PI: Michael Lucey The purpose of this study is to collect and preserve samples of blood, urine, stool, and liver tissue from patients with alcoholic hepatitis to be used in future research studies. The purpose of future studies using these samples will be to develop new methods for diagnosing alcoholic hepatitis and its complications, to develop new markers for disease severity (how bad your disease is), and to identify new targets (treatments and/or blood tests) for improved therapy. We are offering all patients who are seen at UWHC with suspected alcoholic hepatitis the opportunity to participate in this study. Between 18 and 70 years old Active alcohol abuse in the last 3 months Elevated AST/ALT Elevated total bilirubin (>3mg/dL) Liver biopsy or clinical picture consistent with alcoholic hepatitis Have they been admitted for 1 week or less Autoimmune liver disease (ANA>1/320) HIV positive antibodies (if known) Hepatocellular Carcinoma Complete portal vein thrombosis Any extrahepatic terminal disease Pregnant Treated with prednisolone or pentoxifylline >3 days Obeticholic Acid (OCA) for Non-Alcoholic Steatohepatitis (NASH) PI: Adnan Said Evaluate the effect of OCA compared to placebo on histological improvement in NASH by assessing improvement in fibrosis by at least 1 stage without worsening of NASH Fibrosis stage 2 or 3 Is either not taking/on stable doses of: o TZDs or vitamin E for 6 months before Day 1 o Therapies for diabetes (excluding TZDs) and weight loss for 90 days before Day1 o Allowed concomitant medications and supplements for 30 days before Day 1.

2 Stable body weight (ie, not varying by >10% for at least 3 months) Exclusion Criteria: Current or history of significant alcohol consumption for a period > 3 consecutive months within 1 year before Screening Prior or planned bariatric surgery or ileal resection. Evidence of other forms of chronic liver disease including: o Positive test result at Screening for hepatitis B surface antigen (HBsAg) or hepatitis C (HCV) antibody (and positive HCV RNA) o PBC, PSC, autoimmune hepatitis, or overlap syndrome o Alcoholic liver disease o Wilson s disease, hemochromatosis, or iron overload o Alpha-1-antitrypsin (A1AT) deficiency as defined by diagnostic features in liver histology (confirmed by A1AT level below the lower limit of normal [LLN] or exclusion at the Investigator s discretion) o Prior known drug-induced liver injury within 5 years before Day 1 o o Known or suspected HCC History of liver transplant, current placement on a liver transplant list, or current MELD score >12 Histological presence of cirrhosis. Known positivity for HIV Subjects with recent history of significant atherosclerotic cardiovascular disease Volixibat Potassium in Adults with Nonalcoholic Steatohepatitis (NASH) PI: Adnan Said Evaluate the safety, dosing, and efficacy of volixibat potassium in comparison with placebo in adults with nonalcoholic steatohepatitis. Presence of >5% steatosis on screening MRI Histological confirmation of NASH without cirrhosis o NAS >4 with a score of at least 1 in each component (steatosis, lobular inflammation, and hepatocyte ballooning) Presence or history of cirrhosis or evidence of decompensated liver disease o Presence or history of other liver diseases: o Hepatitis B or C o Alcoholic liver disease o Autoimmune hepatitis o PBC o PSC o Hemochromatosis o Wilson s Disease o Alpha-1 antitrypsin deficiency o Bile duct obstruction Treatment with vitamin E, thiazolidinediones, or glucagon-like peptide-1 receptor agonists Uncontrolled thyroid disease Type 1 diabetes HIV Alcohol abuse in the past year Cancer within the past 5 years Inflammatory Bowel Disease (IBD) Studies

3 Methotrexate (MTX)/Sperm Quality in IBD PI: Sumona Saha The purpose of this study is to determine whether the treatment of IBD patients with MTX is associated with an increased risk for infertility using two different criteria for assessing male fertility: the WHO criteria for basic semen analysis and Fourier Harmonic Amplitudes. The latter will be used to describe nuclear shapes and sperm DNA staining intensity as this has been shown in animal models to correlate with male fertility. MTX-exposed male IBD patients (cases) will be compared with age-matched, non-mtx exposed patients (controls). Etrolizumab in Crohn PI: Sumona Saha The target population is patients who have moderate to severely active CD and have had an inadequate response, refractory response or intolerance to CS and/or IS therapy and/or anti- TNFs. The study will be divided into: Screening period of up to 28 days during which patient eligibility will be determined Induction Phase of 14 weeks (Cohort 1: open-label etrolizumab treatment; Cohort 2: randomized to etrolizumab or placebo) Randomization of etrolizumab responders prior to a double-blind Maintenance Phase of 52 weeks or continued blinded treatment with placebo Q4W for 52 weeks for placebo induction responders Diagnosis of Crohn s Disease confirmed by endoscopy or radiography and/or histology at least 6 months prior to randomization into the study with CD involving the ileum and/or colon. Subject must be intolerant or have insufficient response to conventional therapy and have moderately to severely active CD (Crohn s Disease Activity Index (CDAI) score of 220 and 450) at baseline. Subjects must meet concomitant medication criteria described in the protocol. LEGACY Registry Humira Registry for Ulcerative Colitis PI: Freddy Caldera A Long-Term Non-Interventional Registry to Assess Safety and Effectiveness of HUMIRA (Adalimumab) in Patients with Moderately to Severely Active Ulcerative Colitis (UC) See protocol for specific eligibility criteria SECURE Registry PI: Mark Reichelderfer The objective of this registry is to track safety outcomes of patients who have taken Cimzia for the treatment of Crohn s Disease compared to a non- Cimzia control population. Cimzia cohort Patient is receiving treatment with Cimzia for the first time. Patient must receive Cimzia treatment within 2 months of enrollment into the registry. Patient is currently receiving treatment with Cimzia for 12 months. Patients must also receive a Cimzia dose within 2 months following enrollment into the registry. Comparison cohort Patient is switching CD treatments or beginning CD treatment for the first time. Previous Cimzia treatment is prohibited in the comparator group. Patient must receive new CD treatment within 2 months of enrollment into the registry. Patient is currently receiving anti-tnf treatment for 12 months. Patient must receive anti-tnf treatment within 2 months following enrollment into the registry. Patient is currently receiving immunosuppressant therapy for 12 months. Patient must

4 receive immunosuppressant therapy within 2 months following enrollment into the registry. Patient is currently receiving systemic steroid therapy for 12 months. Patient must receive systemic steroid therapy within 2 months following enrollment into the registry. Database & Registry of patients with Gastrointestinal or liver conditions PI: Mark Reichelderfer Registry allows research staff to notify subjects of potential eligibility in current research studies in our office. Database allows us to collect medical record information about their medical history, medication history as well as billing records. Influenza Vaccine in IBD PI: Freddy Caldera The purpose of this study is to help researchers understand how the immune system responds to the influenza vaccine in people with and without IBD. All patients will receive the vaccine and provide blood samples at the following time points: at the time of vaccine administration, 3-weeks post, and 6-months post. Patients on Anti-TNF monotherapy (i.e. Humira, Remicade, Cimzia, etc.) will be randomly assigned to receive either the standard dose or high dose influenza vaccine. Patients on Vedolizumab/Entivyo therapy will be given the standard dose influenza vaccine. PET/MRE PI: Jessica Robbins Determine the diagnostic accuracy of integrated PET/MRE to determine the presence or absence of active inflammation in patients with CD. PET/MRE will occur within 7 days of the scheduled colonoscopy Suspected active CD Scheduled for colonoscopy with biopsy as part of evaluation No contraindications for PET/MR imaging and colonoscopy Age Pregnant or breast-feeding Severe kidney dysfunction (GFR <30mL/min/1.73m2) Mongerson for Crohns PI: Freddy Caldera A Phase 3 randomized, double-blind, placebo-controlled study to investigate the efficacy and safety of GED-0301 for the treatment of subjects with active Crohn s Disease. The active medication is taken orally once daily. The study will be divided into: Screening period of up to 28 days during which patient eligibility will be determined Induction Phase of 12 weeks (Randomly assigned to one of three different treatment groups, or the placebo group) Randomization of GED-0301 responders prior to a double-blind Maintenance Phase of 52 weeks or continued blinded treatment with placebo Q4W for 52 weeks for placebo induction responders Suspected active Crohn s Disease with CDAI >220 and <450, SES-CD >6

5 Failed or experienced intolerance to at least one of the following: aminosalicylates; budesonide; systemic corticosteroids; immunosuppressants; or biologics for the treatment of Crohn s Disease. Local manifestations of Crohn s such as strictures, abscesses, SBS Intestinal resection within 6 months or intra-abdominal surgery within 3 months Ileostomy/colostomy Prior treatment with more than 3 biologics Other GI Studies EoE PI: Sameer Mathur Evaluate maintenance efficacy of oral budesonide slurry in the treatment of EoE Histologic evidence of EOE with peak eosinophil count of 15/HPF, from 2 of the 3 (proximal, mid-, and/or distal) levels of the esophagus at the screening endoscopy History of esophageal dysfunction (dysphagia, vomiting, impaction, ect.) Dysphagia questionnaire during screening indicated subject experienced dysphagia 4 out of 14 days **Non-PPI responsive after 8 weeks of therapy. 1.8 week EGD may count as screening, but patient must remain on PPI for duration of study 2.If previously failed on prior EGD, must be done after min 6 weeks of PPI therapy and be off PPI therapy for 4 weeks prior to screening EGD No change in diet therapy > 3 months No Immunomodulatory therapy within 8 weeks of screening No swallowed or systemic corticosteroids w/in 4 weeks of screening Inhaled steroids not stable for > 3 mo and able to remain on stable dose during study No additions, discontinuations or dose changes of PPI, H2 ant, antacids or Leukotriene inhibitors for any condition (i.e. GERD) within 4 weeks of screening No CYP450 34A inhibitors (grapefruit or ketoconazole) within 2 weeks of baseline visit No high-grade stricture that cannot pass endoscope. No dilations w/in 3 months of screening. No H.Pylori or inflammatory disease (gastritis, IBD, celiac, ect) No varices, Thrush or any disease causing or associated with EoE No acute or chronic viral infections Unstable asthma or UGIB within 4 weeks of screening Sensitive or intolerant to budesonide or similar meds NPS Short Bowel Syndrome Registry PI: Mark Reichelderfer A prospective, multi-center registry for patients with Short Bowel Syndrome to evaluate the longterm safety profile for patients with short bowel syndrome (SBS) who are treated with teduglutide in a routine clinical setting. The primary safety outcome is the occurrence of colorectal cancer in SBS patients with a remnant colon taking teduglutide. Gabapentin for Hyperemesis Gravidarum PI: Sumona Saha

6 The purpose of this study is to compare how effective gabapentin is to a drug called metoclopramide (Reglan) for treatment of hyperemesis gravidarum. One-week double-blinded treatment followed by open-label treatment. Gestational age < 16 weeks Received at least 2 administrations of IV hydration separated by at least 1 week or daily emesis for at least 7 days and 1 IV hydration Failed at least one anti-emetic At least one of the following: o 2-4+ ketonuria o >5% weight loss at any time during pregnancy o Serum potassium <3.4mmol