Nonalcoholic Steatohepatitis Clinical Trial
Official title:
Role of Pioglitazone in the Treatment of Non-alcoholic Steatohepatitis (NASH)
To determine the role of pioglitazone in the treatment of nonalcoholic steatohepatitis (NASH) in patients with glucose intolerance or type 2 diabetes mellitus (T2DM).
Status | Completed |
Enrollment | 55 |
Est. completion date | January 2006 |
Est. primary completion date | November 2005 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | Both |
Age group | 21 Years to 70 Years |
Eligibility |
Inclusion Criteria: 1. Be able to communicate meaningfully with the Investigator and be legally competent to provide written informed consent. 2. Patients must have an age range between 21 to 70 years (inclusive). 3. NASH confirmed by liver biopsy. 4. Subjects must meet the criteria for impaired glucose tolerance (FPG concentration <126 mg/dl and a two hour plasma glucose value during the oral glucose tolerance test [OGTT] =140 but <200 mg/dl) or type 2 diabetes mellitus (FPG concentration = 126 mg/dl or a two hour plasma glucose value during the OGTT =200 mg/dl) (62). Subjects with a FPG greater than 260 mg/dl will be excluded from the study. 5. Diabetic patients will be allowed to be on sulfonylureas or repaglinide but not on metformin, a thiazolidinedione or insulin. Patients must have been on a stable dose of allowed chronic medications for four weeks prior to entering the double-blind treatment period. 6. Female patients must be non-lactating and must either be at least two years post-menopausal, or be using adequate mechanical contraceptive precautions (i.e. intrauterine device, diaphragm with spermicide, condom with spermicide), or be surgically sterilized (i.e. bilateral tubal ligation, bilateral oophorectomy). Female patients who have undergone a hysterectomy are eligible for participation in the study. Female patients (except for those patients who have undergone a hysterectomy or a bilateral oophorectomy) are eligible only if they have a negative pregnancy test throughout the study period. Patients on oral contraceptives or an hormonal implant will be excluded. 7. All participants must have the following laboratory values: Hemoglobin = 13 gm/dl in males, or = 12 gm/dl in females WBC count = 3,000/mm3 Neutrophil count = 1,500/mm3 Platelets = 100,000/mm3 Prothrombin time within 3 seconds of control Albumin =3.0 g/dl Serum creatinine = 1.6 mg/dl Creatinine phosphokinase = 2 times upper limit of normal AST (SGOT) = 2.5 times upper limit of normal ALT (SGPT) = 2.5 times upper limit of normal Alkaline phosphatase = 2.5 times upper limit of normal Exclusion Criteria: 1. Any cause of chronic liver disease other than NASH (such as -but not restricted to- alcohol or drug abuse, medication, chronic hepatitis B or C, autoimmune, hemochromatosis, Wilson's disease, alpha1-antitrypsin deficiency). 2. Any clinical evidence or history of ascitis, bleeding varices, or spontaneous encephalopathy. 3. No past (for at least for 1 year) or current history of alcohol abuse (alcohol consumption greater than one drink per day). 4. Prior surgical procedures to include gastroplasty, jejuno-ileal or jejunocolic bypass. 5. Prior exposure to organic solvents such as carbon tetrachloride. 6. Total parenteral nutrition (TPN) within the past 6 months. 7. Diabetics with a FPG greater than 260 mg/dl on initial visit. 8. Diabetics who are taking metformin, a thiazolidinedione or insulin. 9. Subjects with type 1 diabetes mellitus. 10. Patients on chronic medications with known adverse effects on glucose tolerance levels unless the patient has been on a stable dose of such agents for 4 weeks before entry into the study. Patients on estrogens or other hormonal replacement therapy, tamoxifen, raloxifene, oral glucocorticoids or chloroquine will be excluded. 11. Patients with a history of clinically significant heart disease (New York Heart Classification greater than grade II; more than non-specific ST-T wave changes on EKG), peripheral vascular disease (history of claudication), or pulmonary disease (dyspnea on exertion of one flight or less; abnormal breath sounds on auscultation), will not be studied. |
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
United States | Audie L Murphy VA Hospital | San Antonio | Texas |
Lead Sponsor | Collaborator |
---|---|
The University of Texas Health Science Center at San Antonio | National Institutes of Health (NIH), Takeda Pharmaceuticals North America, Inc. |
United States,
Ali R, Cusi K. New diagnostic and treatment approaches in non-alcoholic fatty liver disease (NAFLD). Ann Med. 2009;41(4):265-78. doi: 10.1080/07853890802552437. Review. — View Citation
Balas B, Belfort R, Harrison SA, Darland C, Finch J, Schenker S, Gastaldelli A, Cusi K. Pioglitazone treatment increases whole body fat but not total body water in patients with non-alcoholic steatohepatitis. J Hepatol. 2007 Oct;47(4):565-70. Epub 2007 Ma — View Citation
Belfort R, Harrison SA, Brown K, Darland C, Finch J, Hardies J, Balas B, Gastaldelli A, Tio F, Pulcini J, Berria R, Ma JZ, Dwivedi S, Havranek R, Fincke C, DeFronzo R, Bannayan GA, Schenker S, Cusi K. A placebo-controlled trial of pioglitazone in subjects — View Citation
Cusi K. Nonalcoholic fatty liver disease in type 2 diabetes mellitus. Curr Opin Endocrinol Diabetes Obes. 2009 Apr;16(2):141-9. doi: 10.1097/MED.0b013e3283293015. Review. — View Citation
Cusi K. Thiazolidinediones in NASH. An odd couple meant to be? J Clin Gastroenterol. 2009 Jul;43(6):503-5. doi: 10.1097/MCG.0b013e3181a15e51. — View Citation
Gastaldelli A, Harrison SA, Belfort-Aguilar R, Hardies LJ, Balas B, Schenker S, Cusi K. Importance of changes in adipose tissue insulin resistance to histological response during thiazolidinedione treatment of patients with nonalcoholic steatohepatitis. H — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Liver histology (Kleiner criteria, Hepatology 2005) | 6 months. | No | |
Secondary | Liver fat content by MRS. | 6 months. | No | |
Secondary | Double-tracer OGTT (EGP, glucose clearance). | 6 months. | No |
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT03375008 -
Predictable MR Index for Nonalcoholic Steatohepatitis (NASH)
|
N/A | |
Recruiting |
NCT05979779 -
Ph 2 Study of the Safety and Efficacy of Three HU6 Dose Levels and Placebo in Nonalcoholic Steatohepatitis
|
Phase 2 | |
Withdrawn |
NCT02769091 -
A Study in Adult Patients With Nonalcoholic Steatohepatitis Who Also Have Type 2 Diabetes
|
Phase 2 | |
Completed |
NCT02654977 -
CLINICAL PROTOCOL to Investigate the Long-term Safety and Efficacy of Metreleptin in Various Forms of Partial Lipodystrophy
|
Phase 2 | |
Recruiting |
NCT05211284 -
Saroglitazar Magnesium 4 mg for NASH in People Living With HIV in the US
|
Phase 2 | |
Completed |
NCT02421094 -
Clinical Trial to Evaluate Efficacy of GR-MD-02 for Treatment of Liver Fibrosis in Patients With NASH With Advanced Fibrosis
|
Phase 2 | |
Completed |
NCT01205087 -
Safety and Efficacy of Oral Administration of Anti-CD3 Monoclonal Antibody (mAb)in Patients With the Metabolic Syndrome
|
Phase 2 | |
Recruiting |
NCT00152711 -
Impact of nCPAP Treatment on Liver Function in Patients With Sleep Apnea Syndrome and Nonalcoholic Steatohepatitis
|
N/A | |
Completed |
NCT02217475 -
Efficacy and Safety Study of Cenicriviroc for the Treatment of Nonalcoholic Steatohepatitis (NASH) in Adult Participants With Liver Fibrosis
|
Phase 2 | |
Completed |
NCT04031729 -
Aspirin for the Treatment of Nonalcoholic Fatty Liver Disease
|
Phase 1/Phase 2 | |
Completed |
NCT03674476 -
An Investigational Study to Evaluate Experimental Medication BMS-986036 in Participants With Different Levels of Kidney Function
|
Phase 1 | |
Recruiting |
NCT03725631 -
Non-invasive Evaluation of Liver Fibrosis, Steatosis, and NASH in NAFLD
|
N/A | |
Terminated |
NCT04565717 -
A Study of ALN-HSD in Healthy Adult Subjects and Adult Patients With Nonalcoholic Steatohepatitis (NASH)
|
Phase 1 | |
Completed |
NCT01679197 -
Clinical Protocol to Investigate the Efficacy of Recombinant Human Leptin (Metreleptin) in Nonalcoholic Steatohepatitis (NASH) or Nonalcoholic Fatty Liver Disease (NAFLD) Associated With Lipodystrophy
|
Phase 2 | |
Active, not recruiting |
NCT05084404 -
Efficacy and Safety of Guanabenz for Nonalcoholic Fatty Liver Disease
|
Phase 2 | |
Active, not recruiting |
NCT02574325 -
A Study to Assess ARI-3037MO on Hepatic Fat Metabolism in Patients With Dysglycemia and Evidence of Hepatic Steatosis
|
Phase 2 | |
Terminated |
NCT00878592 -
Effect of Dietary and Life Style Modification on Post Liver Transplant Obesity
|
N/A | |
Recruiting |
NCT02148471 -
Fatty Acids, Genes and Microbiota in Fatty Liver
|
N/A | |
Completed |
NCT03656744 -
A Study of HTD1801 in Adults With Nonalcoholic Steatohepatitis (NASH) and Type 2 Diabetes Mellitus (T2DM)
|
Phase 2 | |
Completed |
NCT03068078 -
A Reduced-carbohydrate Diet High in Monounsaturated Fats in Type 2 Diabetes
|
N/A |