Brown Adipose Tissue Activity and Thyroid Hormone

Not Applicable

Completed

• Conditions: Hypothyroidism; Hyperthyroidism; Obesity
• Interventions: Other: Levothyroxine therapy (137.75 ± 23.75 μg/day)

• Registration Number: NCT02499471
• Lead Sponsor: Maastricht University Medical Center

Brief Summary

Rationale: During the last decades, research in possible therapies for existing obesity and developmental factors causing obesity has explosively increased. Recently renewed interest aroused for a tissue playing a possible role in both development and therapy for obesity: brown adipose tissue (BAT).

To define the relation between BAT and thyroid hormone, the investigators set up the following research protocol. In this protocol BAT activity will be determined in subjects that underwent thyroidectomy for well-differentiated thyroid carcinoma.

Objective: To study the effect of thyroid hormone and thyroid-stimulating hormone on brown adipose tissue activity.

Study design: Determine BAT activity after thyroidectomy in well-differentiated thyroid carcinoma patients.

Study population: Patients that underwent thyroidectomy for well-differentiated thyroid carcinoma, male and female, aged 18-65 years.

Intervention: FDG-PET-CT-imaging (\[18F\]fluorodeoxyglucose positron-emission-tomography computed-tomography) of BAT activity will be performed under cold stimulation twice.

For patients clinically withdrawn from thyroid hormone suppletion, the first occasion will be in a hypothyroid state within 4-6 weeks after thyroidectomy and the second measurement will take place in a euthyroid state 4 months after the start of thyroid hormone treatment.

For patients receiving recombinant-thyroid-stimulating-hormone injections, the first occasion will be shortly after the injection in a state of high thyroid-stimulating hormone levels. The second measurement will be in a euthyroid state 4 months after the injection.

Main study parameters/endpoints: The main endpoint of this study is the effect of thyroid hormone and thyroid-stimulating hormone on BAT activity in kBq (kilobecquerel) and SUV (standard uptake value). Secondary endpoints are the effects of thyroid hormone and thyroid-stimulating hormone on energy metabolism, body core temperature, skin surface temperatures and skin perfusion.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The absorbed radiation dose from the FDG PET-CT scan after administration of 74 MBq (megabecquerel) of 18F-FDG is 2.8 mSv (miliSievert).

Detailed Description

Not available

Study Timeline

• Study Start: 2012-03
• Primary Completion: 2012-12
• Study Completion: 2014-07
• Status Verified: 2015-07
• Study First Submitted: 2015-07-06
• Study First Submitted QC: 2015-07-14
• Study First Posted: 2015-07-16
• Last Update Submitted: 2015-07-20
• Last Update Posted: 2015-07-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

• Male or postmenopausal females undergoing a total thyroidectomy for well-differentiated thyroid carcinoma
• Age 18-65 years
• Stable physical activity levels for at least six months
• Note: In case of use of anticoagulation, the dose will be adjusted according to plasma thyroid hormone values.

Exclusion Criteria

• Psychologically unstable subjects (as judged by the treating medical specialist)
• Subjects with mental retardation (as judged by the treating medical specialist)
• Subjects with severe behavior disorders (as judged by the treating medical specialist)
• Pregnant subjects
• The use of the following medication is an exclusion criterium; ß-blockers
• Participation in an intensive weight-loss program or vigorous exercise program during the last year before the start of the study
• Abuse of drugs and/or alcohol
• Severe diabetes which requires application of insulin or patients with diabetes-related complications

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Before levothyroxine therapy 137.75 μg	Levothyroxine therapy (137.75 ± 23.75 μg/day)	18F-FDG PET CT scan after mild cold exposure 6.8 ± 2.8 weeks after thyroidectomy, when plasma free T4-levels were at the minimum, before daily levothyroxine therapy 137.75 ± 25.75 μg.
After levothyroxine therapy 137.75 μg	Levothyroxine therapy (137.75 ± 23.75 μg/day)	18F-FDG PET CT scan after mild cold exposure four to six months after the initial measurements, after daily levothyroxine therapy 137.75 μg (fT4 levels 23.1 ± 3.9 pmol/L, TSH 0.5 ± 0.6 mU/L)

Primary Outcome Measures

Name	Time	Method
Cold-induced brown adipose tissue activity	1 day	Measured with 18FDG PET/CT scan after personalised cooling protocol

Secondary Outcome Measures

Name	Time	Method
Body core temperature	1 day	Body core temperature measured with CorTemp telemetric pill
Skin temperatures	1 day	Skin temperatures measured with iButton wireless dataloggers at 14 ISO-defined positions on the skin
Skin perfusion	1 day	Skin perfusion measured with laser-doppler flowmetry on hand and forearm
Energy expenditure	1 day	Energy expenditure measured with ventilated hood system

Trial Locations

Locations (1)

Maastricht UMC; 🇳🇱 Maastricht, Limburg, Netherlands