The TRUST Study - CardioVascular Imaging IMT

Summary

Coronary heart disease (CHD) are the leading causes of mortality and morbidity, particularly with the current context of an aging population. Prospective cohort studies, as well as analyses of pooled individual participant data suggest up to a 60-90% increase in the risk of CHD or HF events among adults with severe SHypo. However, no large randomized controlled trials (RCT) have assessed the impact of thyroid replacement on cardiovascular (CV) imaging outcomes. The goals of this proposal are to address the impact of thyroid replacement on subclinical atherosclerosis. The investigators will conduct a RCT in 185 patients with subclinical hypothyroidism who will be randomly assigned to thyroxine or placebo with an average follow-up of 24 months from baseline. The main outcome will be CV imaging modalities measured by carotid ultrasound at the close-out visit. Assessment of the impact of thyroid replacement on subclinical atherosclerosis within a trial will aid decisions and evidence-based guidelines development to treat a potential modifiable risk factor, such as SHypo.

Conditions

• Thyroid Dysfunction
• Atherosclerosis
• Heart Failure

Interventions

DRUG

Levothyroxine

The intervention will start with Levothyroxine 50 mcg daily (reduced to 25 mcg in subjects \<50 kg of body weight or if known coronary heart disease - previous myocardial infarction or symptoms of angina pectoris) vs. matching placebo; at 3 months, if the serum TSH level is \<0.4 mU/L, dose will be reduced by 25 mcg; TSH \>=0.4 and \<4.6 mU/L, no change to dose; TSH \>=4.6 mU/L, additional 25 mcg. The process will be repeated at 12 months, then annually; mock titration will be performed in the placebo group. The maximum possible dose of Levothyroxine which will be prescribed is 150 mcg (after 4 increments of 25 mcg at 3 months, 1, 2, 3 years; from the starting dose of 50 mcg).

DRUG

Placebo

Control patients will obtain a placebo pill of the same characteristics as the intervention drug, and mock titration will be carried out identically to the intervention drug. Pharmaceutical composition of placebo (100 mg): Lactose monohydrate 66 mg, Maize starch 25 mg, Gelatin 5 mg, Croscarmellose sodium 3.5 mg, Magnesium stearate (vegetable source) 0.5 mg.

Sponsors & Collaborators

• University of Lausanne Hospitals

  collaborator OTHER

• University Hospital, Geneva

  collaborator OTHER

• Insel Gruppe AG, University Hospital Bern

  lead OTHER

Principal Investigators

• Nicolas Rodondi, MD MAS · Clinic for General Internal Medicine, Bern University Hospital Bern

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2016-06-30

Primary Completion

2016-12-31

Completion

2016-12-31

Countries

• Switzerland

Study Locations