Effect of L-thyroxine on progression of Carotid Atherosclerosis in Subclinical Hypothyroidism

ISRCTN	ISRCTN64455739
DOI	https://doi.org/10.1186/ISRCTN64455739
Secondary identifying numbers	MCT-79197

Submission date: 21/05/2008
Registration date: 21/05/2008
Last edited: 04/03/2009

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Circulatory System

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr John David Spence
Scientific

Stroke Prevention & Atherosclerosis Research Centre (SPARC)
Robarts Research Institute
Siebens-Drake Research Bldg.
1400 Western Rd
London, Ontario
N6G 2V2
Canada

Phone	+1 519 663 3113
Email	dspence@robarts.ca

Study information

Study design	Single centre, randomised, double blind (participant, investigator, caregiver, outcome assessor and data analyst), two-arm parallel, placebo-controlled drug intervention
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Scientific title	Effect of L-thyroxine on progression of Carotid Atherosclerosis in Subclinical Hypothyroidism: a single centre, randomised, two-arm parallel, placebo-controlled drug intervention
Study acronym	T4CASH
Study objectives	Primary hypothesis: That treatment of patients with subclinical hypothyroidism with L-thyroxine to achieve a target thyroid stimulating hormone (TSH) less than 2 and greater than 0.4 mIU/L and free thyroxine (FT4) greater than 4 and less than 25 pmol/L, will slow progression of carotid plaque volume and carotid intima-media thickness (IMT), compared to placebo. Secondary hypotheses: That treatment with L-thyroxine will improve control of plasma lipids and homocysteine, and reduce levels of C-reactive protein, weight, waist circumference and insulin resistance. Please note that as of 04/03/2009 the anticipated end date in this record was amended; the previous date at the time of registration was: Initial anticipated end date: 31/07/2007
Ethics approval(s)	Research Ethics Board of the University of Western Ontario gave approval on the 24th June 2004 (ref: 10458).
Health condition(s) or problem(s) studied	Atherosclerosis, subclinical hypothyroidism
Intervention	1. L-thyroxine, beginning at 0.0125 and gradually increased to achieve target TSH level greater than 0.4 and less than 2 and FT4 greater than 4 and less than 25 pmol/L for 18 months 2. Matching placebo, with dummy dose adjustments for 18 months Contact for public queries: Tisha Mabb Lab Manager Stroke Prevention & Atherosclerosis Research Centre (SPARC) Robarts Research Institute Siebens-Drake Research Bldg. 1400 Western Rd London, Ontario N6G 2V2 Canada Email: tisha@robarts.ca
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	L-thyroxine
Primary outcome measure	Rate of progression of carotid plaque volume (mm^3) measured by 3-D ultrasound at baseline and 18 months.
Secondary outcome measures	1. Intima-media thickness (IMT), measured at baseline and 18 months 2. Weight, waist circumference, measured every 6 months 3. Insulin resistance by Homeostasis Model Assessment (HOMA), homocysteine, lipids, measured at baseline and 19 months
Overall study start date	01/07/2006
Completion date	31/07/2010

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Both
Target number of participants	254
Key inclusion criteria	Male or female patients: 1. With subclinical hypothyroidism, defined as a TSH of 3 to 10 mU/L, and a normal serum free thyroxine level (FT4 11 to 25 pmol/L), and 2. Measurable plaque in the carotid arteries 3. Aged greater than or equal to 45 years
Key exclusion criteria	1. Unwilling to give informed consent 2. History of atrial fibrillation 3. Unstable angina, or angina requiring nitroglycerine as often as once a month 4. Unlikely to adhere to the protocol 5. Unlikely to survive 18 months because of severe illness such as cancer 6. At risk of pregnancy
Date of first enrolment	01/07/2006
Date of final enrolment	31/07/2010

Locations

Countries of recruitment

Canada

Study participating centre

Stroke Prevention & Atherosclerosis Research Centre (SPARC)

London, Ontario
N6G 2V2
Canada

Sponsor information

Robarts Research Institute (Canada)
Research organisation

P.O. Box 5015
100 Perth Drive
London, Ontario
N6A 5K8
Canada

Phone	+1 519 663 5777
Email	lchapman@robarts.ca
Website	http://www.robarts.ca/home.php
"ROR"	https://ror.org/01e36dv41

Funders

Funder type

Research organisation

Canadian Institutes of Health Research (CIHR) (Canada) - http://www.cihr-irsc.gc.ca (ref: MCT-79197)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan