Levothyroxine for Non-Alcoholic Fatty Liver Disease (NAFLD)

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.

Conditions

• Non-Alcoholic Fatty Liver Disease
• Diabetes Mellitus, Type 2

Interventions

DRUG

Levothyroxine Sodium

Sponsors & Collaborators

• Singapore Clinical Research Institute

  collaborator OTHER

• Institute for Human Development and Potential (IHDP), Singapore

  collaborator OTHER

• Institute of Bioengineering and Bioimaging (IBB)

  collaborator OTHER_GOV

• Tan Tock Seng Hospital

  collaborator OTHER

• Singapore General Hospital

  collaborator OTHER

• Ng Teng Fong General Hospital

  collaborator OTHER

• Changi General Hospital

  collaborator OTHER

• Khoo Teck Puat Hospital

  collaborator OTHER

• National University Health System, Singapore

  collaborator OTHER

• Duke-NUS Graduate Medical School

  lead OTHER

Principal Investigators

• Paul M Yen, MD · Duke-NUS Graduate Medical School

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

21 Years

Max Age

60 Years

Sex

MALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2014-03-28

Primary Completion

2016-07-28

Completion

2016-07-28