Effects of Exenatide (Byetta®) on Liver Function in Patients With Nonalcoholic Steatohepatitis (NASH)

This study has been completed.
Sponsor:
Information provided by:
Ruhr University of Bochum
ClinicalTrials.gov Identifier:
NCT01208649
First received: September 23, 2010
Last updated: NA
Last verified: September 2010
History: No changes posted
  Purpose

The primary objective is to test the hypothesis that 24 weeks of treatment with exenatide will improve the histological acitvity of NASH (steatosis,necroinflammation, ballooning), summarized in the recently introduced NASH-score in patients with normal, impaired or diabetic glucose tolerance compared to dietary guidance alone.


Condition Intervention Phase
Nonalcoholic Fatty Liver Disease
Drug: Exenatide
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Effects of Exenatide (Byetta®) on Biochemical and Histological Parameters of Liver Function in Patients With Nonalcoholic Steatohepatitis (NASH)

Resource links provided by NLM:


Further study details as provided by Ruhr University of Bochum:

Primary Outcome Measures:
  • histological activity of NASH (steatosis, necroinflammation, ballooning) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Liver fibrosis, as determined using the fibrosis score [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Enrollment: 13
Study Start Date: July 2008
Study Completion Date: September 2010
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Exenatide
Drug (including placebo)
Drug: Exenatide
Exenatide; 48 weeks 10 microg injection s.c., twice daily, before the morning and evening meal with a four week wash-in phase with 5 microg injection s.c.twice daily
Placebo Comparator: Placebo Drug: Exenatide
Exenatide; 48 weeks 10 microg injection s.c., twice daily, before the morning and evening meal with a four week wash-in phase with 5 microg injection s.c.twice daily

Detailed Description:

Non alcoholic steatohepatitis (NASH), a chronic liver disease characterized by insulin resistance, accumulation of hepatic fat and hepatocellular necroinflammation, has been recognized as a leading cause of (cryptogenic) liver cirrhosis in developed countries. Given the rising prevalence of NASH and the associated socio-economic burden associated, novel therapeutic options are warranted. The incretin mimetic Exenatide (Byetta®) exhibits strong glucoregulatory activities through its multiple biological effects. In addition, exenatide treatment has been shown to improve lipid homeostasis and reduce body weight. Since the development of NASH has been tightly linked to the presence of obesity, hyperlipidaemia and diabetes, this study will examine, whether 24 weeks of treatment with exenatide will also result in improvements in liver function in patients with NASH.

60 patients with histologically proven NASH will be randomized to receive either exenatide (2 x 5 µg s.c. for 4 weeks, 2 x 10 µg thereafter) or placebo treatment, in a 1:1 ratio. Liver biopsies will be performed after 24 weeks of treatment. In addition, a non-invasive assessment of hepatic mitochondrial function will be carried-out using a 13C-methionine breath test at baseline, and at weeks 12 and 24. Insulin sensitivity and glucose tolerance will be assessed by a hyperinsulinaemic-euglycaemic clamp (baseline and week 24) and an oral glucose tolerance test (baseline, weeks 12 and 24). Hepatic fat content will be measured by magnetic resonance tomography. Liver enzymes will be monitored closely throughout the study period.

These studies will clarify whether exenatide treatment, in addition to its beneficial effects on glucose homeostasis and body weight, will also result in improvements of liver function in patients with NASH.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Age between 18 and 75 years, inclusive.
  2. Patients present with histologically proven non-alcoholic steatohepatitis ascertained by the single center pathologist between visit 1 and 2
  3. First liver biopsy was obtained not later than 6 months before visit 1
  4. Patients have HbA1c not exceeding 10.0%.
  5. Patients have a history of stable body weight (not varying by >10% for at least 3 months prior to screening

Exclusion Criteria:

  1. Patients are investigator site personnel directly affiliated with the study, or are immediate family of investigator site personnel directly affiliated with the study. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted.
  2. Females of childbearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods (adequate contraceptive measures include sterilisation, hormonal intrauterine devices, oral contraceptives, sexual abstinence or vasectomised partner). A male subject who is sexually active and has not been surgically sterilised must be informed that he must either use a condom during intercourse, ensure that his partner practices contraception, or he must refrain from sexual intercourse during the trial and until 1 month after completion of the trial. This is to prevent the possibility of a pregnancy from spermatocytes that can potentially be damaged by trial medication. It is strongly recommended that the female partners use a highly effective contraception (Pearl Index < 1%).
  3. Patients have participated in an interventional medical, surgical, or pharmaceutical study (a study in which an experimental, drug, medical, or surgical treatment was given) within 30 days prior to screening. This criterion includes drugs that have not received regulatory approval for any indication at the time of study entry.
  4. Patients with evidence of viral or autoimmune hepatitis (positive testing for HBsAG, anti-HCV or anti-HIV, pos. AMA-screen, ANA-titer > 1:160)
  5. Patients with inherited liver diseases (e.g. Wilson's disease, Hemochromatosis)
  6. Patients have alcohol consumption (>20 g daily for males and >10 g daily for females)
  7. Patients have decompensated liver cirrhosis (Child-Pugh score >7)
  8. Patients have alanine aminotransaminase (ALT) greater than ten times the upper limit of the reference range.
  9. Patients have had greater than three episodes of severe hypoglycemia within 6 months prior to screening.
  10. Patients are undergoing therapy for a malignancy, other than basal cell or squamous cell skin cancer.
  11. Patients have cardiac disease that is Class III or IV, according to the New York Heart Association criteria.
  12. Patients have a known allergy or hypersensitivity to exenatide, or excipients contained in these agents.
  13. Patients have or had concomitant medication with thiazolidinediones.
  14. Patients have a history of renal transplantation or are currently receiving renal dialysis or have serum creatinine >1.8 mg/dL for males and greater than or equal to >1.5 mg/dL for females.
  15. Patients have known hemoglobinopathy or chronic anemia
  16. Patients are receiving chronic (lasting longer than 2 weeks) systemic glucocorticoid therapy (excluding topical and inhaled preparations) or have received such therapy within 2 weeks immediately prior to screening.
  17. Patients have used any prescription drug to promote weight loss within 3 months prior to screening.
  18. Patients have any other condition (including known drug or alcohol abuse or psychiatric disorder) that precludes them from following and completing the protocol, in the opinion of the investigator.
  19. Patients fail to satisfy the investigator of suitability to participate for any other reason.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01208649

Locations
Germany
Department of Medicine I; University Hospital St. Josef-Hospital
Bochum, Germany, 44791
Sponsors and Collaborators
Ruhr University of Bochum
Investigators
Study Director: Wolfgang E. Schmidt, Prof. Dr. Ruhr-University Bochum
Principal Investigator: Wolfgang E. Schmidt, Prof. Dr. Ruhr-University Bochum
  More Information

No publications provided

Responsible Party: Prof. Dr. med. Wolfgang E. Schmidt; Director Department of Medicine l;, Universitiy Hospital; Ruhr-University Bochum; Gudrunstr. 56; 44791 Bochum; Germany
ClinicalTrials.gov Identifier: NCT01208649     History of Changes
Other Study ID Numbers: H80-MC-O008
Study First Received: September 23, 2010
Last Updated: September 23, 2010
Health Authority: Germany: Ethics Commission
Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Ruhr University of Bochum:
exenatide
hepatic steatosis
insulin resistance
insulin sensitizers
nonalcoholic fatty liver disease
- GLP1-Analog

Additional relevant MeSH terms:
Fatty Liver
Liver Diseases
Digestive System Diseases
Exenatide
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 22, 2014