Using thyroid hormone to treat liver disease in veterans
Low Dose Thyroid Hormone, Mitochondrial Fatty Acid Oxidation, and Treatment of Nonalcoholic Steatohepatitis (NASH)
This study is testing if low doses of thyroid hormone can help veterans with liver disease called NASH feel better and improve their liver health.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 128 (estimated) |
| Ages | 18 Years to 75 Years |
| Sex | All |
| Sponsor | VA Office of Research and Development Federal |
| Locations | 1 site (Columbia, Missouri) |
| Trial ID | NCT05526144 on ClinicalTrials.gov |
What this trial studies
This clinical trial aims to evaluate the effectiveness of low dose thyroid hormone in treating nonalcoholic steatohepatitis (NASH) among veterans. The study will involve administering titrated doses of thyroid hormone to participants with biopsy-proven NASH and monitoring for histological improvements in liver condition. The trial is structured in two stages, beginning with a proof of concept followed by an interim analysis to determine if the study should continue. The primary outcome will be assessed through changes in the nonalcoholic fatty liver disease score (NAS).
Who should consider this trial
Good fit: Ideal candidates for this study are overweight or obese veterans with biopsy-proven NASH and features of metabolic syndrome.
Not a fit: Patients who do not have NASH or those with significant alcohol intake or other liver diseases may not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment could provide a new therapeutic option for veterans suffering from NASH, potentially improving liver health and reducing the risk of severe complications.
How similar studies have performed: While there is limited research on the use of thyroid hormone for NASH, preliminary studies suggest potential benefits, making this approach novel and exploratory.
Eligibility criteria
Show full inclusion / exclusion criteria
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
Where this trial is running
Columbia, Missouri
- Harry S. Truman Memorial, Columbia, MO — Columbia, Missouri, United States (Recruiting)
Study contacts
- Principal investigator: Jamal A Ibdah, MD PhD — Harry S. Truman Memorial, Columbia, MO
- Study coordinator: Adam T Whaley-Connell, DO MSPH
- Email: Adam.Whaley-Connell@va.gov
- Phone: (573) 814-6552
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.