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Trial record 1 of 3 for:    16447287 [PUBMED-IDS]
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Levothyroxine for Non-Alcoholic Fatty Liver Disease (NAFLD)

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ClinicalTrials.gov Identifier: NCT03281083
Recruitment Status : Terminated (Difficult recruitment and end of funding.)
First Posted : September 13, 2017
Last Update Posted : September 14, 2017
Sponsor:
Collaborators:
Singapore Clinical Research Institute
Singapore Institute for Clinical Sciences
Singapore Bioimaging Consortium
Tan Tock Seng Hospital
Singapore General Hospital
Ng Teng Fong General Hospital
Changi General Hospital
Khoo Teck Puat Hospital
National University Health System, Singapore
Information provided by (Responsible Party):
Paul M. Yen, Duke-NUS Graduate Medical School

Brief 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.


Condition or disease Intervention/treatment Phase
Non-Alcoholic Fatty Liver Disease Diabetes Mellitus, Type 2 Drug: Levothyroxine Sodium Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 29 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Single arm study.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Effects of 4-month Therapy of Levothyroxine on Non-Alcoholic Fatty Liver Disease (NAFLD) and Diabetes Control in Diabetic Patients
Actual Study Start Date : March 28, 2014
Actual Primary Completion Date : July 28, 2016
Actual Study Completion Date : July 28, 2016


Arm Intervention/treatment
Experimental: Levothyroxine (LT4)
Levothyroxine sodium (LT4) dose titrated at TSH 0.34 - 1.70mIU/L during maximum 12 weeks, followed by a maintenance phase of 16 weeks using the dose necessary for titration.
Drug: Levothyroxine Sodium
Other Name: H03AA01




Primary Outcome Measures :
  1. Liver fat content [ Time Frame: 16 weeks ]
    To ascertain whether administration of LT4 for 16 weeks by titrating the serum TSH to 0.34 mIU/L - 1.7 mIU /L reduces liver fat content by at least 3% among patients with type II DM as measured by functional MRI.


Secondary Outcome Measures :
  1. HbA1c [ Time Frame: 16 weeks ]
    To ascertain whether administration of LT4 for 16 weeks by titrating the serum TSH to 0.34mIU/L - 1.7 mIU/L can improve glycemic control in Type II diabetic patients with NAFLD measured by reduction in HbA1c.

  2. Lipid profile [ Time Frame: 16 weeks ]
    To ascertain whether administration of LT4 for 16 weeks by titrating the serum TSH to 0.34mIU/L - 1.7 mIU/L can improve serum lipid profile in Type II diabetic patients with NAFLD as measured by total serum cholesterol, HDL, LDL and total triglycerides.

  3. Abdominal fat [ Time Frame: 16 weeks ]
    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 the proportion of liver fat over body fat, which is reflected by fat in abdominal subcutaneous and visceral tissues, among patients with type II diabetes as measured by functional MRI on abdomen.



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Ages Eligible for Study:   21 Years to 60 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male between 21 to 60 years of age
  2. Diagnosed with stable Type II diabetes mellitus (DM) with no changes in oral hypoglycaemic medications or dose for the last 2 months from the time of start LT4, and if on insulin < 10 units change in insulin dosage, documented by patient's medical records. The most recent HbA1C for the last 6 months from the time of start LT4 should be no more than 10%.
  3. If the subject is on statin medication, there should be no change in the medication or dose of statin for the last 2 months from the time of start LT4
  4. Baseline ALT <3 times upper limit of normal as per the institution's specified reference range , with a liver ultrasound showing presence of fatty liver (liver ultrasound will not be requested if a prior scan has been done within the past 6 months from the time of screening)
  5. The IHL content on the MRI/MRS should be more than 10% to allow enrollment in the trial.
  6. Baseline TSH levels between 1 - 10 mIU/L
  7. Baseline heart rate <90 beats/min
  8. Ability to provide informed consent

Exclusion Criteria:

  1. Subject with history of viral hepatitis (except subject with history of viral A hepatitis or history of viral E hepatitis that was diagnosed at least 1 year before), hepatocellular carcinoma, liver cirrhosis, heart disease, osteoporosis, hyper/hypothyroidism, anxiety disorder, Graves' disease, thyroid/liver surgery, lactose intolerance, or malabsorption
  2. Baseline estimated glomerular filtration rate (eGFR) < 60 ml/min
  3. Currently on or within 6 months from the time of screening on either thyroxine, thiazolidinedione (TZD), oral T4/T3, anticoagulants (coumadin and warfarin), anti-viral drugs such as the protease inhibitors (ritonavir, indinavir, lopinavir), phenytoin, colestyramine, aluminium containing drugs (antacids, sucralfate), salicylates (> 100mg/day), dicumarol, furosemide, or sevelamer
  4. Consumption of ethanol greater than 30g/day (i.e. 3 drinks/day or 21 drinks/week, with about 10g of alcohol per drink)
  5. Has advanced liver disease with a baseline NAFLD fibrosis score of >0.675 (stage 3 or 4 fibrosis)
  6. Has an implant or device in the body which is not safe for MRI scan
  7. Baseline ECG findings considered to be clinically significant (e.g., ischemic changes, arrhythmias) by the Investigator(s)
  8. Subject with history of claustrophobia
  9. Baseline free T4 of more than the institution's specified reference range If a sole blood test result is deemed borderline according to the laboratory reference interval and not clinically significant, the investigator is authorized to exercise discretion.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03281083


Sponsors and Collaborators
Duke-NUS Graduate Medical School
Singapore Clinical Research Institute
Singapore Institute for Clinical Sciences
Singapore Bioimaging Consortium
Tan Tock Seng Hospital
Singapore General Hospital
Ng Teng Fong General Hospital
Changi General Hospital
Khoo Teck Puat Hospital
National University Health System, Singapore
Investigators
Principal Investigator: Paul M Yen, MD Duke-NUS Graduate Medical School

Publications:

Responsible Party: Paul M. Yen, Professor, Duke-NUS Graduate Medical School
ClinicalTrials.gov Identifier: NCT03281083     History of Changes
Other Study ID Numbers: MRN-01-NAFLD-01
First Posted: September 13, 2017    Key Record Dates
Last Update Posted: September 14, 2017
Last Verified: September 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Paul M. Yen, Duke-NUS Graduate Medical School:
Non-Alcoholic Fatty Liver Disease
Diabetes Mellitus, type 2
Thyroid hormone
Levothyroxine

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Liver Diseases
Fatty Liver
Non-alcoholic Fatty Liver Disease
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Digestive System Diseases