Recruiting
Phase 2

Thyroid Hormone

Sponsor:

VA Office of Research and Development

Code:

NCT05526144

Conditions

Nonalcoholic Steatohepatitis

Liver Fibrosis

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

Synthroid

Placebo

Study Details

Brief summary:

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.

Conditions

Nonalcoholic Steatohepatitis

Liver Fibrosis

Study ID

NCT05526144

Start date

Apr 1, 2023

Status verified date

Feb, 2026

Completion date

Dec 31, 2029

Anticipated

Primary completion date

Dec 31, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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
  • Patients who are treated with vitamin E or pioglitazone should be on stable doses for at least 6 months before enrollment
  • Features of metabolic syndrome: 3 or more (central obesity, hypertension, low HDL, high triglycerides, high fasting glucose)
  • Scheduled for a medically indicated, diagnostic liver biopsy
  • Female patients are eligible if they are of reproductive potential and have a negative serum pregnancy test (beta human chorionic gonadotropin), are not breastfeeding, and do not plan to become pregnant during the study and agree to use two highly effective birth control methods during the study OR if they are not of child-bearing potential (i.e., surgically \[bilateral oophorectomy, hysterectomy, or tubal ligation\] or naturally sterile \[> 12 consecutive months without menses\])

  • Highly effective birth control methods include condoms with spermicide, diaphragm with spermicide, hormonal and nonhormonal intrauterine device, hormonal contraception (estrogens stable for at least 3 months), a vasectomized male partner, or sexual abstinence (defined as refraining from heterosexual intercourse), from screening, throughout the study, and for at least 30 days after the last dose of study drug administration
  • Reliance on abstinence from heterosexual intercourse is acceptable only if it is the patient's habitual practice
  • If a patient is on digitalis and amiodarone, he/she is expected to use/continue these medications throughout the treatment period only after consultation with their cardiologist for monitoring and dose adjustments if necessary

Exclusion Criteria:

  • 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
  • Pregnancy
  • History of malignant hypertension
  • Uncontrolled hypertension (either treated or untreated) defined as systolic blood pressure > 160 mm Hg or a diastolic blood pressure > 100 mm Hg at screening
  • New York Heart Association Class III or IV heart failure or known left ventricular ejection fraction < 30%
  • Uncontrolled cardiac arrhythmia, including confirmed QT interval corrected using Fridericia's formula (QTcF) > 450 msec for males and > 470 msec for females at the screening electrocardiogram (ECG) assessment
  • History of myocardial infarction, unstable angina, percutaneous coronary intervention, coronary artery bypass graft, or stroke within at least 3 months prior to randomization
  • History of high degree AV block (Mobitz II or complete) in the absence of a pacemaker
  • Patients with uncorrected adrenal insufficiency
  • Patients who are on tricyclic or tetracyclic antidepressants or ketamine, if they are unwilling and/or unable to discontinue these medications to allow adequate washout prior to randomization
  • Patients who are on Teduglutide or Midodrine

Study Design

Enrollment

128 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

placebo comparator: Placebo group

Placebo group will receive placebo tablets

active comparator: Study group

Study group will receive Synthroid (Levothyroxine) 25, 50, or 75 mcg daily

Interventions

Synthroid

Synthroid 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

Placebo 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.

Primary outcome measure

  • Improvement in Nonalcoholic fatty liver disease activity score (NAS) by 2 points [ Time Frame: 12 months ]

Central Contacts and Locations

Central contacts

Adam T Whaley-Connell, DO MSPH

(573) 814-6552Adam.Whaley-Connell@va.gov

Jennifer A Atherton

(573) 814-6000Jennifer.Atherton@va.gov

Locations

Harry S. Truman Memorial, Columbia, MO

Recruiting

Columbia, Missouri, United States, 65201-5275

Contacts

Adam T Whaley-Connell, DO MSPH

573-814-6552Adam.Whaley-Connell@va.gov

Jennifer A Atherton

(573) 814-6000Jennifer.Atherton@va.gov

Principal Investigator:

Jamal A Ibdah, MD PhD

More Information

Sponsor

VA Office of Research and Development

Last update posted

Feb 19, 2026

Last verified

Feb, 2026

Keywords

  • Thyroid hormone
  • Nonalcoholic fatty liver disease (NAFLD)
  • Nonalcoholic steatohepatitis (NASH)
  • Mitochondrial fatty acid oxidation

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by VA Office of Research and Development on 2026-02-19.