Levothyroxine for Non-Alcoholic Fatty Liver Disease (NAFLD)
Status:
Terminated
Trial end date:
2016-07-28
Target enrollment:
Participant gender:
Summary
Background: Non-alcoholic fatty liver disease (NAFLD) is a spectrum of disorders
characterized by lipid accumulation in hepatocytes. Evidence shows that thyroid hormone might
be beneficial for this condition.
Objective: To determine whether low dose levothyroxine (LT4) therapy may be a potential
treatment for diabetic patients with NAFLD in a single arm study.
Primary: To ascertain whether administration of LT4 for 16 weeks by titrating the serum
thyroid stimulating hormone (TSH) to 0.34 mIU/L - 1.7 mIU /L reduces liver fat content by at
least 3% among patients with type II diabetes as measured by functional MRI.
Secondary: To ascertain whether administration of LT4 for 16 weeks by titrating the serum TSH
to 0.34 mIU/L - 1.7 mIU /L can improve glycemic control as measured by reduction in
glycosylated hemoglobin (HbA1c), improve serum lipid profile in Type II diabetic patients
with NAFLD as measured by total serum cholesterol, high-density lipoprotein (HDL),
low-density lipoprotein (LDL) and total triglycerides (TG) and reduce the proportion of liver
fat over body fat, which is reflected by fat in abdominal subcutaneous and visceral tissues,
as measured by functional MRI on abdomen.
Subjects and Centres: A total of 50 eligible adult diabetic men with NAFLD will be recruited
from 6 centres in Singapore - Changi General Hospital (CGH), Singapore General Hospital
(SGH), Tan Tock Seng Hospital (TTSH), National University Health System (NUHS), Khoo Teck
Puat Hospital (KTPH), Jurong Health (JH)
Eligible patients: Males between 21 to 60 years of age diagnosed with stable Type II diabetes
mellitus (DM) with a baseline alanine aminotransferase (ALT) < 3 times upper limit of normal
as per the institution's specified reference range, with a liver ultrasound (US) showing
presence of fatty liver and baseline Thyroid stimulating hormone (TSH) levels between 1 - 10
mIU/L.
Treatment: Low dose levothyroxine (LT4) for 16 weeks, not including the 12 weeks of pre-study
titration of LT4 in order to attain target TSH level of 0.34-1.70 mIU/L.
Statistical Analysis: The absolute change in liver fat content from baseline (primary
endpoint) will be analyzed using one-sample two-sided t-test at a 5% significance level. The
same test will be applied to secondary endpoints. Mean, standard deviation and 95% confidence
interval will be calculated for primary endpoint and secondary endpoints.
Phase:
Phase 2
Details
Lead Sponsor:
Duke-NUS Graduate Medical School
Collaborators:
Changi General Hospital Institute of Bioengineering and Bioimaging (IBB) Khoo Teck Puat Hospital National University Health System, Singapore Ng Teng Fong General Hospital Singapore Bioimaging Consortium Singapore Clinical Research Institute Singapore General Hospital Singapore Institute for Clinical Sciences Tan Tock Seng Hospital