A double-blind, randomized, placebo-controlled, parallel group study of rimonabant 20 mg daily for the treatment of Type 2 diabetic patients with nonalcoholic steatohepatitis (NASH)

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 720

Inclusion Criteria

1. Patients who are at least 18 years of age and with a diagnosis of NASH by liver biopsy performed within last 6 months (based on pre-defined histological criteria as confirmed by a central pathologist)

2. Confirmed Type 2 DM diagnosed by fasting plasma glucose = 126 mg/dl or 2-hour post load glucose = 200 mg/dl during an OGTT (equivalent of 75 g anhydrous glucose in water) of at least 6 months duration.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
;
1. Patients who are at least 18 years of age and with a diagnosis of NASH by liver biopsy performed within last 6 months (based on pre-defined histological criteria as confirmed by a central pathologist)

2. Confirmed Type 2 DM diagnosed by fasting plasma glucose = 126 mg/dl or 2-hour post load glucose = 200 mg/dl during an OGTT (equivalent of 75 g anhydrous glucose in water) of at least 6 months duration.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Exclusion criteria related to study methodology
1. Refusal or inability to give informed consent to participate in the study

2. Average alcohol ingestion > 21 units/wk (males) or > 14 units/wk (females) [self-administered quantity-frequency and 7-day recall tests and confirmed by a family member]

3. History of or presence of Type 1 diabetes mellitus (requirement for insulin replacement and presence of autoantibodies, e.g., antipancreatic islet cell, insulin autoantibodies, tyrosine phosphate autoantibodies or GADAb)

4. Hemoglobin A1C > 8.5.

5. Other cause of chronic liver disease and/or hepatic steatosis:
- Wilson’s Disease
- Alpha-1-Antitrypsin deficiency
- Viral hepatitis
- Primary Biliary Cirrhosis
- Autoimmune hepatitis
- Genetic iron overload
- History of sleep apnea (unless on Constant Positive Airway Pressure therapy)
- History of or current HIV infection
- Hypo- or hyper-thyroidism

6. Any contraindication to liver biopsy based on local standard for pre-liver biopsy risk assessment (as examples,: presence of a bleeding dyscrasia, platelets < 50-75K, prothrombin time > 3 sec above control as measured locally during pre-biopsy evaluation of coagulation parameters)

7. History of or planned gastrointestinal bypass surgery/intervention (i.e., bariatric surgery)

8. Hepatic Cirrhosis with a Child-Pugh classification of B or C (score > 6)

9. Concomitant Hepatocellular Carcinoma (HCC) (i.e., AFP > 100 ng/mL on screening Liver Disease Panel or otherwise unexplained liver mass visualized on ultrasound or computed tomography examination of the liver)

10. Previous hepatic transplantation

11. Recent significant weight loss (> 5% TBW within previous 6 months)

12. ALT or AST > 10 x ULN at screening or within 3 months of screening

13. Recent (within 6 months of baseline liver biopsy and screening visit) or concomitant use of agent known to cause hepatic steatosis:
- corticosteroids
- amiodarone
- methotrexate
- tamoxifen
- tetracycline
- high dose estrogens (standard HRT and oral contraceptive doses allowed)
- valproic acid

14. Recent (within 3 months of baseline liver biopsy and screening visit) change in anti-diabetes treatment, such as a change in dose-regimen of anti-diabetes agent or introduction of new- antidiabetes agent (a specific diabetes medication /treatment page will be included in the CRF).

15. Recent (within 3 months of baseline liver biopsy and screening visit) change in dose/ regimen or introduction of:
- Vitamin E, Vitamin C
- betaine, s-adenosyl methionine (SAM), ursodeoxycholate (UDCA)
- silymarin (silybin)
- fibrate
- statin
- pentoxyfilline
- angiotensin II inhibitor

16. Recent (within 3 months of baseline liver biopsy and screening visit) change in dose/ regimen or introduction of weight loss agent such as:
- orlistat
- sibutramine
- rimonabant

17. Any situation that in the Investigator’s opinion, may interfere with optimal study participation such as alcohol or drug abuse, domicile too distant from study site, potential non-compliance during the study or inability to cooperate because of a language problem or poor mental development

18. Participation in any clinical study of an investigational agent within 30 days or five half-lives of the investigational agent, whichever is longer

19. Presence of clinically relevant cardiovascular, pulmonary, gastro-intestinal, hepatic, renal, metabolic, hematological, neurological, psychiatric, systemic, ocular, gynecologic (if female), or any acute infectious;
Exclusion criteria related to study methodology
1. Refusal or inability to give informed consent to participate in the study