Thyroid Hormone for Treatment of Nonalcoholic Steatohepatitis in Veterans

Launched by VA OFFICE OF RESEARCH AND DEVELOPMENT · Aug 30, 2022

Keywords

ClinConnect Summary

This clinical trial is exploring whether low doses of thyroid hormone can help treat Nonalcoholic Steatohepatitis (NASH) in Veterans. NASH is a serious liver condition that can lead to more severe liver diseases and is particularly common among military and Veteran populations. The study aims to see if this hormone can improve how the body breaks down fat in the liver, potentially leading to better health outcomes. The trial will be conducted in two stages, starting with a proof of concept to determine if the treatment is promising enough to continue.

To participate, individuals need to be Veterans aged between 65 and 74 who are overweight or obese, have a body mass index (BMI) of 25.9 or higher, and meet certain health criteria. This includes having stable type 2 diabetes and not consuming alcohol excessively. Participants can expect to undergo a medically necessary liver biopsy and receive the thyroid hormone treatment while being monitored for their health. It's important for potential participants to know that there are specific health conditions that might prevent them from joining the study, so discussing eligibility with a healthcare provider is crucial.

Gender

ALL

Eligibility 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