Thyroid Hormone for Treatment of Nonalcoholic Steatohepatitis in Veterans
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-75
SponsorVA Office of Research and Development
About this trial
Nonalcoholic steatohepatitis (NASH) is the aggressive form of nonalcoholic fatty liver disease, which is rapidly becoming a worldwide public health problem. It is more common in the military and Veteran population compared to the general US population. NASH may progress to end-stage liver disease and primary liver cancer, and hence there is critical need for effective treatment. The goal of this clinical trial is to test whether low dose thyroid hormone administered to Veterans diagnosed with NASH can be an effective therapy mediated by improvement in breaking down fat in the mitochondria. The study will be conducted in two stages, the first stage is for proof of concept to be followed by interim analysis. If the interim analysis supports the merit for continuing the study, the clinical trial will proceed to stage 2 for continuation. This study will provide new information and strategies for treatment of NASH using low dose thyroid hormone that will be highly relevant and impactful to the health of the Veteran population.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Men and women (pre- and post-menopausal)
Overweight/obese subjects with body mass index (BMI) at or above 25.9 kg/m2
Alcohol intake < 20 grams per day
Patients with type 2 diabetes on stable doses of antidiabetic medication for at least 3 months before enrollment
Disqualifiers
Other causes of hepatitis including hepatitis B & C, autoimmune hepatitis, hemochromatosis, celiac disease, Wilson's disease, alpha-1-antitrypsin deficiency, medication-induced hepatitis
Alcohol consumption of 20 g/d or more
Patients with cirrhosis, bilirubin of 1.3 mg/dL or more, and INR of 1.3 or more
Evidence of Portal hypertension
Trial design
Design model
Parallel
Treatments tested in this trial
Synthroid
DrugSynthroid tablets 25 mcg. Subjects in the study group will receive Synthroid at a titrated dose of 25 mcg (one tablet), 50 mcg (two tablets), or maximum of 75 mcg (3 tablets) daily for one year duration that will maintain TSH at normal level.
Placebo
DrugPlacebo tablets 25 mcg daily. Subjects in the placebo group will receive placebo tablets at a dose of 25 mcg (one tablet), 50 mcg (two tablets), or maximum of 75 mcg (3 tablets) daily for a one year duration.
Treatment groups
128 Participants
are divided into 2 treatment groupsGroup A: Placebo groupPlacebo comparator 1 intervention
Group B: Study groupActive comparator 1 intervention
Trial outcomes
Primary outcomes
1
Improvement in Nonalcoholic fatty liver disease activity score (NAS) by 2 points
To examine the efficacy of daily low dose Synthroid, using a dose-titration strategy based on serum thyroid stimulating hormone (TSH), on the histological progression of nonalcoholic steatohepatitis (NASH) in Veterans with normal serum TSH levels and biopsy-proven NASH, and to compare the treated patients with Veterans on placebo. Liver biopsies will be obtained at baseline (Week 0) and at end of treatment (Week 52). Nonalcoholic fatty liver disease activity score (NAS) will be assessed in baseline and post treatment liver biopsies and improvement in NAS will be compared between study group on active treatment and placebo group.
Time frame
12 monthsSecondary outcomes
1
Proportion of subjects experiencing improvement in biopsy-determined fibrosis by at least one stage
The stage of liver fibrosis will be assessed in the study subjects at baseline and post intervention. Improvement in the stage of fibrosis will be compared between the placebo and study groups.
Time frame
12 months2
Improvement in mitochondrial fatty acid oxidation
Effect of Synthroid on mitochondrial fatty acid oxidation will be assessed by measurement of complete mitochondrial fatty acid oxidation in liver tissue obtained at baseline and post intervention (52 weeks) in study and placebo groups.
Time frame
12 months3
Improvement in mitochondrial biogenesis
Effect of Synthroid on mitochondrial biogenesis will be assessed by measurement of PCG-1alpha (peroxisome-proliferator-activated receptor gamma coactivator 1 alpha) gene expression in the liver tissue at baseline and post intervention at 52 weeks in the study and placebo groups.
Time frame
12 months4
Improvement in mitochondrial mitophagy
Effect of Synthroid on mitochondrial mitophagy will be assessed by measurement of BNIP3 (BCL2 interacting protein 3) gene expression in the liver tissue at baseline and post intervention at 52 weeks in the study and placebo groups.
Time frame
12 monthsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Source ClinicalTrials.gov