Clinical Trial: The Role of Thyroid Status in Regulating Brown Adipose Tissue Activity, White Adipose Tissue Partitioning and Resting Energy Expenditure

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: The Role of Thyroid Status in Regulating Brown Adipose Tissue Activity, White Adipose Tissue Partitioning and Resting Energy Expenditure

Brief Summary:

To determine how thyroid status regulates the relationship between brown adipose tissue (BAT) volume/activity, white adipose tissue (WAT) partitioning and basal metabolic rate (BMR) in hyperthyroid patients transitioning to euthyroidism via antithyroid drugs.

To compare euthyroid outcomes (BAT, WAT, BMR, body composition, body weight and insulin resistance) achieved by hypothalamus-pituitary-thyroid (HPT) set point vs. normal ranges of plasma free thyroxine 4 (FT4) and throxine stimulating hormone (TSH).


Detailed Summary:

Study Visit 1 is meant to confirm if participant's hyperthyroidism is due to Graves' disease via a blood test called TSH receptor autoantibody (TRAb). This is a standard test that doctors will routinely order as part of clinical practice to diagnose the cause of participant's hyperthyroidism and is not part of the research procedure. If this TRAb blood test has been done before participants have been referred to the endocrinology clinic at TTSH, investigators will review that result and decide if a repeat test is needed. If participants are confirmed by blood tests to have Graves' disease type of hyperthyroidism, participants are eligible to take part in this study. However, approximately 2 teaspoons (~ 10 mL) of blood will be taken for baseline thyroid function test just prior to the initiation of anti-thyroid drugs. Pre-menopausal women will also undergo a urine pregnancy test to exclude pregnancy prior to participation at study entry. Once participants have consented to participate in this study, participants will be randomized to receive either carbimazole (CMZ) or thiamazole (TMZ) and dosed according to a set point-based strategy (SPT) or by a strategy that moves participant's thyroid function test away from the set point (ASP) but still keeping participant's thyroid hormone levels within the normal ranges. Randomization means assigning participants to one of two groups by chance, like tossing a coin or rolling dice. This study is also a double-blind study, which means that apart from the research coordinator, neither participants nor the investigators will know which of the two treatment arms participants are assigned to. Up to a maximum of three investigators will be designated as the antithyroid drug (ATD) dose prescriber, and the investigators will be in charge of deciding on the ATD dose required based on the latest FT4, FT3 and TSH blood test results though investigators will not know who the test results belo
Sponsor: Clinical Nutrition Research Centre, Singapore

Current Primary Outcome:

  • Thyroid function test (serum free thyroxine (FT4) and serum thyroid stimulating hormone (TSH) via a Set-point (SPT) approach [ Time Frame: 6 months of treatment with an anti-thyroid drug ]
    Hyperthyroid patients will be treated until their serum FT4 (measured in pmol/L) and serum TSH (measured in mIU/L) normalize to euthyroidism as defined by a computed set point. The set point is a pair of FT4 and TSH which represents the optimized euthyroid state that is unique to every individual.
  • Thyroid function test (serum free thyroxine (FT4) and serum thyroid stimulating hormone (TSH) via Away from set point (AST) approach [ Time Frame: 6 months of treatment with an anti-thyroid drug ]
    Hyperthyroid patients will be treated till their serum FT4 (measured in pmol/L) and serumTSH (measured in mIU/L) normalize within the lab reference ranges but off the computed set point.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Fat volume- Brown adipose tissue (BAT) [ Time Frame: 6 months of treatment with an anti-thyroid drug ]
    The above volumes will be measured at start of treatment and at 6 months by MRI (fat fraction for BAT) - volumes in mL.
  • Fat volume- White adipose tissue (WAT) [ Time Frame: 6 months of treatment with an anti-thyroid drug ]
    The above volumes will be measured at start of treatment and at 6 months by MRI (standard MRI for WAT) - volumes in mL.
  • Energy expenditure [ Time Frame: 6 months of treatment with an anti-thyroid drug ]
    The metabolic rate (measured from the energy expenditure) will be measured using the whole body calorimeter in kcal/day.
  • Body composition [ Time Frame: 6 months of treatment with an anti-thyroid drug ]
    The subjects will have a body composition evaluated by DXA at the start of treatment and 6 months post-treatment when they are rendered euthyroid. WE will measure lean mass, fat mass and bone mass.
  • Infrared thermography (IRT) [ Time Frame: 6 months of treatment with an anti-thyroid drug ]
    We will measure BAT activity using IRT. This will be expressed in terms of temperature change in degrees Celsius and heat power change in watts (W).


Original Secondary Outcome: Same as current

Information By: Clinical Nutrition Research Centre, Singapore

Dates:
Date Received: February 9, 2017
Date Started: June 1, 2017
Date Completion: June 1, 2019
Last Updated: February 21, 2017
Last Verified: February 2017