Ignite Creation Date:
2025-12-25 @ 2:28 AM
Ignite Modification Date:
2026-06-27 @ 3:33 AM
Study NCT ID:
NCT02832934
Status:
COMPLETED
Last Update Posted:
2017-02-28
First Post:
2016-07-12
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
The TRUST Study - CardioVascular Imaging IMT
Sponsor:
Insel Gruppe AG, University Hospital Bern
Organization:
Study Overview
Official Title:
Impact of Thyroid Hormone Replacement on Progression of Atherosclerosis : a Randomized Placebo-Controlled Trial in Older Adults With Subclinical Hypothyroidism.
Status:
COMPLETED
Status Verified Date:
2017-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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.
Detailed Description:
Background: Coronary heart disease (CHD) and heart failure (HF) are the leading causes of mortality and morbidity, particularly with the current context of an aging population. Subclinical hypothyroidism (SHypo), defined as elevated serum TSH levels with normal thyroxine values, is common in older adults (5-10%). 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 (largest trial to date: 45 participants). Imaging endpoints are especially well-suited for early trials with investigational therapies for HF treatment and prevention, as well as validated and strong surrogate markers of clinical outcomes.
Specific Aims: The goals of this proposal are to address the impact of thyroid replacement on subclinical atherosclerosis.
Methods: 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 (4 death and 17 withdrawal). The main outcome will be CV imaging modalities measured by carotid ultrasound at the close-out visit. Ultrasound of carotid intima media thickness (CIMT) will be used to assess subclinical atherosclerosis and plaque burden. All images will be centralized at the core lab for a blinded and standardized interpretation.
Expected value of the proposed project: Controversies persist regarding the indications for screening and treatment of SHypo due to the lack of an appropriately powered RCT addressing the impact of thyroid replacement on CV outcomes. 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. The strengths of this study include the combination of: 1) High feasibility of the project in collaboration with the largest RCT on SHypo making it possible to investigate the mechanisms of associations with CV disease; 2) Innovative project with combined CV imaging to assess subclinical atherosclerosis with thyroid replacement therapy vs. placebo; 3) Excellent power given the large sample size and participants' older age. The sample size for this proposal will be 5-fold higher than previous small trials of thyroid replacement on CV outcomes and is comparable to statin trials showing a positive impact on CIMT. The collaboration of CV imaging modalities expertise with the ongoing largest trial on SHypo, is a unique opportunity to address the clinical and scientific issue of the impact of SHypo on the CV system.
Specific Aims: The goals of this proposal are to address the impact of thyroid replacement on subclinical atherosclerosis.
Methods: 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 (4 death and 17 withdrawal). The main outcome will be CV imaging modalities measured by carotid ultrasound at the close-out visit. Ultrasound of carotid intima media thickness (CIMT) will be used to assess subclinical atherosclerosis and plaque burden. All images will be centralized at the core lab for a blinded and standardized interpretation.
Expected value of the proposed project: Controversies persist regarding the indications for screening and treatment of SHypo due to the lack of an appropriately powered RCT addressing the impact of thyroid replacement on CV outcomes. 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. The strengths of this study include the combination of: 1) High feasibility of the project in collaboration with the largest RCT on SHypo making it possible to investigate the mechanisms of associations with CV disease; 2) Innovative project with combined CV imaging to assess subclinical atherosclerosis with thyroid replacement therapy vs. placebo; 3) Excellent power given the large sample size and participants' older age. The sample size for this proposal will be 5-fold higher than previous small trials of thyroid replacement on CV outcomes and is comparable to statin trials showing a positive impact on CIMT. The collaboration of CV imaging modalities expertise with the ongoing largest trial on SHypo, is a unique opportunity to address the clinical and scientific issue of the impact of SHypo on the CV system.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 974a | OTHER_GRANT | VELUX STIFTUNG | View |