Clinical Trials Register

Summary
EudraCT Number:	2011-000942-39
Sponsor's Protocol Code Number:	NL34476.068.11
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2011-04-04
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Netherlands - Competent Authority

A.2

EudraCT number

2011-000942-39

A.3

Full title of the trial

Effects of thyroid hormone treatment on mitochondrial function, ectopic fat accumulation, insulin sensitivity and brown adipose tissue in type 2 diabetes mellitus.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

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

A.3.2

Name or abbreviated title of the trial where available

Thyroid and type 2 diabetes

A.4.1

Sponsor's protocol code number

NL34476.068.11

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	CTMM, the Center for Translational Molecular Medicine
B.1.3.4	Country	Netherlands
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	CTMM
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	CTMM
B.5.2	Functional name of contact point	Erna Erdsieck-Ernste
B.5.3	Address:
B.5.3.1	Street Address	High Tech Campus 12a (HTC) Room 133
B.5.3.2	Town/ city	Eindhoven
B.5.3.3	Post code	5656AG
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	+3140277 43 95
B.5.5	Fax number	+314025 15 455
B.5.6	E-mail	erna.erdtsieck-ernste@CTMM.nl

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Euthyrox
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck BV
D.2.1.2	Country which granted the Marketing Authorisation	Netherlands
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	levothyroxine sodium
D.3.2	Product code	RVG 09009
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	LEVOTHYROXINE SODIUM
D.3.9.1	CAS number	55-03-8
D.3.9.2	Current sponsor code	MERCK
D.3.9.3	Other descriptive name	thyroxine
D.3.9.4	EV Substance Code	SUB08495MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	25 to 100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

This trial includes overweight patients with both hypothyroidism and type 2 diabetes.

E.1.1.1

Medical condition in easily understood language

This study includes patients with Thyroid dysfunction, overweight and sugar disease.

E.1.1.2

Therapeutic area

Body processes [G] - Metabolic Phenomena [G03]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	13.1
E.1.2	Level	PT
E.1.2	Classification code	10021114
E.1.2	Term	Hypothyroidism
E.1.2	System Organ Class	10014698 - Endocrine disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	13.1
E.1.2	Level	LLT
E.1.2	Classification code	10045242
E.1.2	Term	Type II diabetes mellitus
E.1.2	System Organ Class	10027433 - Metabolism and nutrition disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The main objective of this study is to investigate whether thyroid hormone replacement therapy will improve
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.

E.2.2

Secondary objectives of the trial

A secondary aim of this research project is whether thyroid hormone replacement therapy decreases
mitochondrial membrane potential and lowers the production of reactive oxygen species.

E.2.3

Trial contains a sub-study

E.3

Principal 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.

E.4

Principal 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 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, 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

E.5 End points

E.5.1

Primary end point(s)

The primairy endpoints are changes in insulin sensitivity, lipid accumulation and mitochondrial function.

E.5.1.1

Timepoint(s) of evaluation of this end point

At baseline (before starting the medication) and after 3 months of treatment.

E.5.2

Secondary end point(s)

The secundairy endpoints are changes in activity of brown adipose tissue mitochondrial membrane potential production of radical oxygen species.

E.5.2.1

Timepoint(s) of evaluation of this end point

At baseline (before starting the medication) and after 3 months of treatment.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

E.6.5

Efficacy

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

etiology

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

The end of the trial is planned to be at the 31 december of 2013. A extension for the study will be requested by the Medical Ethical Commission when the study is not finalized by then.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Thyroid hormone replacement therapy will be carefully monitored, evaluated and documented during the study period. This documentation will be provided to the doctor responsible for further treatment of the patients.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2011-06-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-03-31

P. End of Trial
P.	End of Trial Status	Ongoing

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials