Effects of thyroid hormone treatment on energyproduction, fat storage and sugar disease.

• Conditions: This trial includes overweight patients with both hypothyroidism and type 2 diabetes.; MedDRA version: 13.1Level: PTClassification code 10021114Term: HypothyroidismSystem Organ Class: 10014698 - Endocrine disorders; MedDRA version: 13.1Level: LLTClassification code 10045242Term: Type II diabetes mellitusSystem Organ Class: 10027433 - Metabolism and nutrition disorders; Therapeutic area: Body processes [G] - Metabolic Phenomena [G03]

• Registration Number: EUCTR2011-000942-39-NL
• Lead Sponsor: CTMM, the Center for Translational Molecular Medicine

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-04-04
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 17

Inclusion Criteria

-Male or postmenopausal females
-Age 40-65 years
-Body mass index (BMI) < 40 and > 27 kg/m2
-Stable dietary habits (no weight loss/gain >3 kg in the last 6 months)
-Stable physical activity levels for at least six months
-Newly diagnosed hypothyroid, non-insulin dependent type 2 diabetic patients having TSH values higher then > 4.0 mU/l and lowered concentrations of free T4 < 8.0 pmol/l.
-Type 2 diabetic patients using sulphonylurea and or metformin therapy for at least six months with a constant dose for at least two months.
-Hypothyroid diabetic patients due to Hashimoto disease (TPO > 100 IE/ml; Tg > 344 IE/ml), should have no auto-antibodies against glutamic acid decarboxylase (GAD), IA-2 and insulin to exclude type 2 polyglandular autoimmune syndrome (PGAII) (to exclude type 1 diabetes).
-Type 2 diabetic patients should have a HbA1c level < 8.0%
-Type 2 diabetic patients will be included when having no diabetes-related co-morbidities like cardiovascular diseases, diabetic foot, polyneuropathy, retinopathy.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 17
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

-Unstable body weight
-Participation in an intensive weight-loss program or vigorous exercise program during the last year before the start of the study
-Medical history including active cardiovascular disease, i.e. history of coronary artery disease (i.e. history of angina pectoris, percutaneous transluminal coronary angioplasty or coronary artery bypass grafting) or cardiac arrhythmias.
-Liver disease or liver dysfunction (ALT>2.5 x increased)
-Impaired renal function (kreatinine> 120 umol/L)
-Systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg
-Hb <7.4 mmol/l (12 g/dl) in women, and <8.1 mmol/l (13 g/dl) in men
-Abuse of drugs and/or alcohol
-Contraindications for MRI scanning (please see appendix III: MRI contraindication questionnaire)
-Patients with history of thyroid cancer
-Patients using a and/or ß blockers
-Severe diabetes which requires application of insulin or patients with diabetes-related complications
-History of psychiatric disease
-Diabetes related co-morbidities like cardiovascular diseases, diabetic foot, polyneuropathy, retinopathy.
-Use of medications known to interfere with glucose homeostasis (i.e. corticosteroids, thiazolidendiones)
-Hypothyroid diabetic patients due to Hashimoto disease with positive test values for auto-antibodies against GAD, IA-2 and insulin to exclude type 1 diabetes.
-Use of anticoagulantia, other than platelet aggregation inhibitors.
-Patients that have donated blood in the past 6 months

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The main objective of this study is to investigate whether thyroid hormone replacement therapy will improve<br>insulin resistance and lower ectopic fat accumulation in the muscle, liver and heart. Furthermore, we would like to examine whether thyroid hormone replacement therapy enhances mitochondrial function via the process of mitochondrial uncoupling and changes the activity of brown adipose tissue.;Secondary Objective: A secondary aim of this research project is whether thyroid hormone replacement therapy decreases<br>mitochondrial membrane potential and lowers the production of reactive oxygen species.;Primary end point(s): The primairy endpoints are changes in insulin sensitivity, lipid accumulation and mitochondrial function.;Timepoint(s) of evaluation of this end point: At baseline (before starting the medication) and after 3 months of treatment.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): The secundairy endpoints are changes in activity of brown adipose tissue mitochondrial membrane potential production of radical oxygen species.;Timepoint(s) of evaluation of this end point: At baseline (before starting the medication) and after 3 months of treatment.