Effects of Alanine in Patients With Nonalcoholic Steatohepatitis

Keith D Lindor, M.D.

Status

Completed

Conditions

Nonalcoholic Steatohepatitis

Treatments

Drug: L-alanine

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00586885

1753-03

Details and patient eligibility

About

Purpose of this study is to assess the therapeutic efficacy of L-alanine in improving biological and histological findings by administrating 6-18g/day L-alanine for one year. We will also assess the safety and toxicity profile of long-term administration of L-alanine.

Enrollment

9 patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Males and females, age between 18 and 75
Histological diagnosis of steatohepatitis with or without fibrosis made within one year of entry
Transaminase levels (ALT or AST) more than 1.5 times the upper normal limit on at least two occasions with one assessment in three months or more prior to treatment of this study
Previous and current alcohol consumption less than 20g per day by patient-provided information.
Written informed consent specific for this protocol available prior to entry.
Patients with diabetes and on stable medical management for six months prior to entry and an anticipated stable program throughout the study will be eligible. Medications that may be used include insulin, biguanides and sulfonylureas.
Patients with congestive heart failure, hypertension and arrhythmia controlled by medications and without cardiac episodes during the past 6 months will be eligible.

Exclusion criteria

Any causes for liver disease other than nonalcoholic steatohepatitis that are confirmed by patient history, laboratory data, or histological data
Decompensated liver disease based on laboratory data, or clinical manifestations
1. Hemoglobin <11.0g/dl for male, <10.0 g/dl for female
2. White blood cells <2000 /mm3
3. Platelet count <50,000/mm3
4. Prothrombin time >INR 1.5
5. Total Bilirubin >2.0 g/dl
6. Albumin <3.0/dl
7. The presence of ascites
8. The presence of bleeding varices
9. The presence of spontaneous encephalopathy
Any previous experimental treatment of NASH within the past 3 months such as betaine, thiazolidinediones, α-tocopherol, or UDCA
Pre-existing diseases/situations that could interfere with the results or the completion of this trial.
Uncontrolled diabetes mellitus meeting following criteria in previous 3 months
1. Fasting blood sugar >200 mg/dl
2. Hemoglobin A1c >12%
Renal or liver transplant patients
Renal dysfunction in previous 3 months

a) CCr <50ml/min
Severe cardiovascular dysfunction in previous 6 months
Congestive heart failure
Uncontrolled hypertension
Uncontrolled arrhythmia
Patients with hyperlipidemia on a medical program for control of lipids which has had a change in drug treatment in the proceeding six months or with anticipated changes in the year of the study.
Chronic pulmonary disease such as COPD requiring corticosteroid therapy in previous 3 months
Active autoimmune or immunologically mediated diseases including systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel diseases in previous 12 months
Previous (in three years) or present malignant disease except for non-melanoma skin cancer
Untreated hyperthyroidism and hypothyroidism
Substance abuse of oral, I.V., or inhaled drugs.
If patients with history of substance abuse are considered as participants in this trial, patients must have abstained from using the abused substance for at least one year.
Patients receiving methadone within the past 6 months are also excluded.
Any other conditions that would make the patients unsuitable for enrollment in the opinion of the investigator in terms of interference in completing the trial and/or results of trial.
Pregnant women
Unwillingness of patients and /or partner to use contraceptive during treatment and for 3 months after discontinuation of treatment.