DiabetesPhase 4NCT01379170
Thyroid Study Type 2 Diabetes Mellitus (T2DM)
A Phase 4 study testing Euthyrox (levothyroxine) in people with Diabetes and Hypothyroidism, run by Maastricht University Medical Center at 1 site in Netherlands.
Trial summary
Background of the study: Thyroid hormones, thyroxine (T4) and triiodothyronine (T3), are known to promote weight loss, which could be beneficial for treating obesity, and type 2 diabetes. Read more about this study
- Who is it for?
- Ages 40 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Diabetes, Hypothyroidism
- What is being tested?
- Euthyrox (levothyroxine)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteNetherlands
- Study dates
- Jun 2011to Dec 2014
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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 (creatinine > 120 umol/L)
- Systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg
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- 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 α and/or β 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, thiazolidinediones)
- 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 anticoagulants, other than platelet aggregation inhibitors.
- Patients that have donated blood in the past 6 months
Trial locations and contacts
1 site in 1 country.
Netherlands1 site, 1 recruiting
- Recruiting
Maastricht University Medical Centre
Maastricht, Limburg, 6200MD
Evie Broeders, MD, +31 43 3884254, e.broeders@maastrichtuniversity.nl
About this study
Official title: Effects of Thyroid Hormone Treatment on Mitochondrial Function, Ectopic Fat Accumulation, Insulin Sensitivity and Brown Adipose Tissue in Type 2 Diabetes Mellitus
Background of the study:
Thyroid hormones, thyroxine (T4) and triiodothyronine (T3), are known to promote weight loss, which could be beneficial for treating obesity, and type 2 diabetes. Thyroid hormone treatment stimulates energy expenditure resulting in increased body heat production, in which brown adipose tissue play an important role. It is hypothesized that thyroid hormones would induce increased energy expenditure via a process called mitochondrial uncoupling, thereby creating an inefficient energy status. Indeed, an in vivo study showed a 70% increased flux through the tricarboxylic acid cycle (TCA) and an unchanged ATP synthesis rate upon T3 treatment in lean, healthy young men. The disproportionate increase in TCA flux compared with ATP synthesis suggests increased mitochondrial uncoupling. It is however unknown whether increased mitochondrial uncoupling would increase fat oxidation and exerts favorable effects on insulin sensitivity. There is compelling evidence that type 2 diabetic patients have high levels of fat accumulation in non-adipose tissues, such as skeletal muscle, heart and liver. Ectopic fat accumulation is related to insulin resistance, however, why this fat accumulates in peripheral organs is not known. Recently, studies reported compromised mitochondrial oxidative capacity in type 2 diabetic patients and first-degree relatives of diabetic patients, suggested to play an important role. Therefore, subjects suffering from overweight and/or type 2 diabetes with overt hypothyroidism form an interesting group for examining the metabolic effects of thyroid hormone treatment, as less is known about the effects of thyroid hormone treatment in these groups.
Read more
Objective of the study:
The purpose of this study is to evaluate whether thyroid hormone replacement therapy in type 2 diabetic patients suffering from overt hypothyroidism, will improve muscular mitochondrial function, lower ectopic fat accumulation in muscle and liver, increase brown adipose tissue activity and enhance insulin sensitivity.
Study design:
Type 2 diabetic patients diagnosed with hypothyroidism will undergo 3 months of thyroid hormone replacement therapy (THRT) (Euthyrox®, Merck, Germany). Patients will be metabolically characterized (such as insulin sensitivity and fat accumulation in peripheral tissues) before and after this thyroid hormone replacement therapy.
Study population:
17 type 2 diabetic patients diagnosed with overt hypothyroidism (9 from the Netherlands, 8 from Germany which will only do the PET-CT)
Primary study parameters/outcome of the study:
Thyroid hormone-induced change in whole body insulin sensitivity (change in insulin-stimulated glucose disposal) and muscle mitochondrial function.
Secondary study parameters/outcome of the study (if applicable):
Thyroid hormone-induced change of lipid content in skeletal muscle and liver and brown adipose tissue activity.
- Conditions
- Diabetes, Hypothyroidism
- Being tested
- Euthyrox (levothyroxine)
- Keywords
- brown adipose tissue, mitochondrial dysfunction, insulin resistance
- Medical subject headings
- Diabetes Mellitus, Hypothyroidism, Mitochondrial Diseases, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Euthyrox (levothyroxine)Drug
Also called Euthyrox/levothyroxine
A dose of 25 μg per day of Euthyrox® will be administered orally during the first week and will be increased to 50 μg per day during the second week and to 75-100 μg per day in the third week depending on TSH, free T4 and T3 concentrations monitored throughout the treatment period. Patients will be instructed to take Euthyrox® after an overnight fast, 30 min before breakfast in the morning daily. After 3 months, free T4 and total T3 concentration must be in the normal range (free T4: 8.0-26 pmol/l, T4: 60-140 nmol/l and T3 1.2 - 3.4 nmol/l) and TSH 0.4-2.5 mU/l.
| Study group | Role | What they receive |
|---|---|---|
| Type 2 diabetes, de novo hypothyrodism treatment | Experimental | Type 2 diabetic patients with de novo hypothyroidism will be included in this arm and will receive 3 months of treatment with Euthyrox (standard protocol). Receives: Drug: Euthyrox (levothyroxine) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Thyroid hormone-induced change in whole body insulin sensitivity (change in insulin-stimulated glucose disposal) and muscle mitochondrial function
see title
Measured: 3 months
Secondary outcomes (1)
Thyroid hormone-induced change of lipid content in skeletal muscle and liver and brown adipose tissue activity
see title
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2011 (estimated)
- Study startJun 2011
- Primary completionDec 2014 (estimated)
- Study completionDec 2014 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for DiabetesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Maastricht University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01379170
- Sponsor's protocol ID
- MEC10-3-085
- Status last verified
- May 2013
- First submitted
- 21 Jun 2011
- Last updated
- 14 May 2013
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Thyroid Hormone Treatment on Mitochondrial Function, Ectopic Fat Accumulation, Insulin Sensitivity and Brown Adipose Tissue in Type 2 Diabetes Mellitus
- ClinicalTrials.gov ID
- NCT01379170
- Acronym / sponsor ID
- MEC10-3-085
- Conditions
- Diabetes, Hypothyroidism
- Keywords
- brown adipose tissue, mitochondrial dysfunction, insulin resistance
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 17 participants (estimated)
- Lead sponsor
- Maastricht University Medical CenterUniversity, hospital or other
- Study start
- Jun 2011
- Primary completion
- Dec 2014 (estimated)
- Study completion
- Dec 2014 (estimated)
- First posted
- 23 Jun 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background of the study:
Thyroid hormones, thyroxine (T4) and triiodothyronine (T3), are known to promote weight loss, which could be beneficial for treating obesity, and type 2 diabetes. Thyroid hormone treatment stimulates energy expenditure resulting in increased body heat production, in which brown adipose tissue play an important role. It is hypothesized that thyroid hormones would induce increased energy expenditure via a process called mitochondrial uncoupling, thereby creating an inefficient energy status. Indeed, an in vivo study showed a 70% increased flux through the tricarboxylic acid cycle (TCA) and an unchanged ATP synthesis rate upon T3 treatment in lean, healthy young men. The disproportionate increase in TCA flux compared with ATP synthesis suggests increased mitochondrial uncoupling. It is however unknown whether increased mitochondrial uncoupling would increase fat oxidation and exerts favorable effects on insulin sensitivity. There is compelling evidence that type 2 diabetic patients have high levels of fat accumulation in non-adipose tissues, such as skeletal muscle, heart and liver. Ectopic fat accumulation is related to insulin resistance, however, why this fat accumulates in peripheral organs is not known. Recently, studies reported compromised mitochondrial oxidative capacity in type 2 diabetic patients and first-degree relatives of diabetic patients, suggested to play an important role. Therefore, subjects suffering from overweight and/or type 2 diabetes with overt hypothyroidism form an interesting group for examining the metabolic effects of thyroid hormone treatment, as less is known about the effects of thyroid hormone treatment in these groups.
Objective of the study:
The purpose of this study is to evaluate whether thyroid hormone replacement therapy in type 2 diabetic patients suffering from overt hypothyroidism, will improve muscular mitochondrial function, lower ectopic fat accumulation in muscle and liver, increase brown adipose tissue activity and enhance insulin sensitivity.
Study design:
Type 2 diabetic patients diagnosed with hypothyroidism will undergo 3 months of thyroid hormone replacement therapy (THRT) (Euthyrox®, Merck, Germany). Patients will be metabolically characterized (such as insulin sensitivity and fat accumulation in peripheral tissues) before and after this thyroid hormone replacement therapy.
Study population:
17 type 2 diabetic patients diagnosed with overt hypothyroidism (9 from the Netherlands, 8 from Germany which will only do the PET-CT)
Primary study parameters/outcome of the study:
Thyroid hormone-induced change in whole body insulin sensitivity (change in insulin-stimulated glucose disposal) and muscle mitochondrial function.
Secondary study parameters/outcome of the study (if applicable):
Thyroid hormone-induced change of lipid content in skeletal muscle and liver and brown adipose tissue activity.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Type 2 diabetes, de novo hypothyrodism treatment | Experimental | Drug: Euthyrox (levothyroxine)Type 2 diabetic patients with de novo hypothyroidism will be included in this arm and will receive 3 months of treatment with Euthyrox (standard protocol). |
Who may qualify
- Ages
- 40 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (18 listed)
- 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 (creatinine > 120 umol/L)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Euthyrox (levothyroxine)Also: Euthyrox/levothyroxineA dose of 25 μg per day of Euthyrox® will be administered orally during the first week and will be increased to 50 μg per day during the second week and to 75-100 μg per day in the third week depending on TSH, free T4 and T3 concentrations monitored throughout the treatment period. Patients will be instructed to take Euthyrox® after an overnight fast, 30 min before breakfast in the morning daily. After 3 months, free T4 and total T3 concentration must be in the normal range (free T4: 8.0-26 pmol/l, T4: 60-140 nmol/l and T3 1.2 - 3.4 nmol/l) and TSH 0.4-2.5 mU/l. | Drug | Type 2 diabetes, de novo hypothyrodism treatment |
Primary outcome
Thyroid hormone-induced change in whole body insulin sensitivity (change in insulin-stimulated glucose disposal) and muscle mitochondrial function
Time frame: 3 months
see title
1 secondary outcome
Thyroid hormone-induced change of lipid content in skeletal muscle and liver and brown adipose tissue activity
Time frame: 3 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2013.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Euthyrox (levothyroxine) in people with Diabetes and Hypothyroidism, run by Maastricht University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 14 May 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Evie Broeders, MD (+31 43 3884254, e.broeders@maastrichtuniversity.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Thyroid hormone-induced change in whole body insulin sensitivity (change in insulin-stimulated glucose disposal) and muscle mitochondrial function (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2013.