A Phase 1 interventional study of Thyroid hormone T3 and Control Group in Heart Failure, sponsored by Emory University. Completed at 2 sites in United States. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2026-08-04.
Sponsored by Emory University · Phase 1, Interventional, and Treatment
This study aims to determine whether giving triiodothyronine (T3), a thyroid hormone, is safe and helps improve symptoms and signs of heart failure.
Participants who are enrolled to receive the study drug will be admitted to the General Clinical Research Center (GCRC) for 5 days for oral thyroid hormone treatment and monitoring. They will have 4 additional follow-up visits over the next year. Participants who are not enrolled to receive the study drug will not be admitted but will have similar follow-up visits in the outpatient setting.
If this study finds that patients have improved heart function after thyroid hormone treatment without unacceptable side effects, it could lead to a new treatment for patients with heart failure.
About six million adults in the United States have heart failure (HF). Myocardial ischemic injury is the most common trigger of HF, and most deaths after a myocardial infarction (MI) are preceded by HF. Treatment for HF with reduced ejection fraction (HFrEF) consists of beta-adrenergic receptor antagonists, antagonists of the renin-angiotensin-aldosterone system (ACEI, ARB, angiotensin receptor neprilysin inhibition), aldosterone antagonists, and Sodium-glucose Cotransporter-2 (SGLT-2) antagonists. Despite these guideline-directed therapies, 1 in 2 HF patients dies within 5 years of diagnosis, a death rate similar to that of some cancers. Thus, the development of next-generation therapies to treat HF represents an important unmet clinical need.
The overarching goal of these preclinical and anticipated clinical studies is to develop translatable strategies, using transient triiodothyronine (thyroid hormone T3) administration in patients with HF receiving beta1-adrenergic receptor (AR) blocker therapy (metoprolol succinate) with other HF medications, to permanently improve left ventricular (LV) contractile function by regenerating cardiac muscle.
The most-cited basis of ineffective cardiac regeneration in mammals is the low proliferative capacity of adult cardiomyocytes. The investigators have sought to understand the most important aspects of these processes to develop therapies that can be used to build or rebuild heart muscle in diseased hearts.
In brief, the investigators' preclinical studies show that T3+metoprolol therapy regenerates heart muscle by increasing cardiomyocytes around the scar and increasing the left ventricular ejection fraction (LVEF), thereby restoring LV wall contractility in the scar region. De novo cardiomyogenesis requires neovascularization along with cardiomyocyte proliferation so that the nutrient and oxygen demands of the expanding myocardium are met. Our preliminary studies also show that in chronic post-MI hearts, the mid-apical LV myocardium was repopulated with cardiomyocytes following T3+metoprolol therapy, and that these cardiomyocytes were not hypertrophied (data not shown). Importantly, the researchers found no significant differences in mid-apical capillary-to-cardiomyocyte ratios between T3+metoprolol-treated post-MI hearts and uninjured age-matched controls.
Together, these findings suggest lasting regenerative repair of hearts with severe preexisting ischemic injury after a brief period of T3+metoprolol combination therapy. Importantly, over the course of this 5-month follow-up, the research team did not observe any signs of arrhythmias or an increase in mortality in mice treated with T3+metoprolol combination therapy. Low free T3 levels (\<2.5pg/ml) are found in approximately 10% of patients with early HF and 58% of patients with late HF, and are more frequently observed in patients with HF of NYHA class III-IV. This is likely secondary to the upregulation of type 3 iodothyronine deiodinase. Low T3 levels correlate with LVEF and BNP levels in HF. Importantly, a low T3 level in addition to BNP levels is an independent predictor of worse outcomes in patients with HF and after MI. The T3 production rate in normal humans is 16 ± 3 μg/m2 BSA/day. In patients with HF and low T3 levels, 20 μg/m2 BSA/d T3 increased T3 levels significantly to within the normal range. The rate of infusion on days 2 and 3 was then lowered to 13.4 μg/m2 BSA/day on average to maintain this level. There was a concomitant decrease in T4 (10.9 to 9.6 pg/ml) and thyroid-stimulating hormone (TSH) from 2.43 to 0.55 IU, but they remained in the normal range.
Based on previous experience in patients with HF, researchers propose to employ a 5-day oral treatment with L-T3 in gradually increasing doses to rapidly establish higher T3 levels in patients with stable ischemic HF with an EF≤40%. The team anticipates that doses of T3 used in the proposed studies will not cause tachycardia or dysrhythmias. Even though the final L-T3 dose proposed here is twice that previously used, the team believes that the possibility of inducing tachycardia is likely to be low because of the concomitant treatment with metoprolol succinate, a B1-selective (cardioselective) adrenergic receptor blocker therapy. Researchers do not anticipate the development of other hyperthyroid symptoms in these patients, as L-T3 administration is only for a brief period of 5 days.
5,701 studies on the registry are indexed under Heart Failure; 1,220 are open to participants now.
This study's enrollment of 14 is below the median of 72 across 3,736 interventional studies indexed under Heart Failure.
Browse Heart Failure studies →Emory University is the lead sponsor of 1,386 studies on the registry; 236 are open to participants now.
Of its 229 completed or terminated interventional studies of FDA-regulated products, 174 (76%) have results posted.
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Exclusion Criteria:
In Phase IA two participants (1 and 2) will receive ascending dose levels of the study drug (5 µg T3 orally twice daily for the first 2 days and 10 µg T3 orally twice daily for the next 3 days).
Drug: Thyroid hormone T3
In Phase IB, dose adjustments will be calculated while accounting for laboratory and safety data from the first two participants (Phase IA) for the remaining 3 participants within the treatment arm of Phase I. Participants 3 to 5 will receive 10 µg T3 orally twice daily on day 1 and 20 µg T3 twice daily from day 2 to 5.
Drug: Thyroid hormone T3
The control group will have testing as the experimental group but will not be given any medications.
Other: Control Group
Participants will be admitted to the General Clinical Research Center (GCRC) for up to 5 days and will receive study medication twice a day. Participants will receive oral T3 under the supervision of the Principal Investigator or qualified co-investigators at the GCRC. The study drug will be given within 30 days after enrollment.
Also known as: Triiodothyronine, Cytomel
The control group will have testing and study procedures as per protocol but will not be admitted to the General Clinical Research Center (GCRC) and will not receive the study medication. After completion of phase I, participants will be permitted to enroll in Phase II.
Also known as: No intervention
Changes in the presence of clinical arrhythmias
An electrocardiogram will be performed during each study visit and the presence of any Clinical arrhythmias such as ectopy, atrial fibrillation, ventricular arrhythmias, ICD firing will be documented. \*Days 1 through 5 apply only to those who are admitted to the GCRC unit.
Time frame: Baseline, Days 1*, 2*, 3*, 4*, 5*, 6 weeks, 3 months, 6 months, 12 months
The number of participants with Angina, acute coronary syndrome, death during the first week
The total number of subject's events during the first week of the treatment period will be recorded
Time frame: During the first week of treatment period
Change in left ventricular ejection fraction (LVEF)
An echocardiogram will be performed at specific study visits and LVEF will be measured
Time frame: Baseline, Day 45, Day 90
Change in 6-minute walk distance (6MWD)
Two 6-minute walk tests will be completed at least 2 hours apart to establish a baseline. The mean of the 2 distances will be used as the baseline. The six-minute walk test requires a 100-ft hallway. This test measures the distance that a patient can quickly walk on a flat, hard surface in a period of 6 minutes. The six-minute walk test serves as a standardized test for functional capacity quantification of HF patients and is predictive of adverse cardiovascular outcomes. Most patients do not achieve maximal exercise capacity during the 6-minute walk test; instead, they choose their own intensity of exercise and can stop and rest during the test.
Time frame: Baseline, Day 45, Day 90
Changes in New York Heart Association (NYHA) classification
Participants will be asked about exertional symptoms for NYHA functional categorization of HF symptoms at all time points. Symptom-based scores range from I to IV. The NYHA classification system also includes an objective assessment of cardiovascular disease severity, which ranges from A-D. Differences between treatment and control arms over time will be analyzed as well as within arms over time.
Time frame: Baseline, Day 45, Day 90
Change in Kansas City Cardiomyopathy Questionnaire (KCCQ)
This is a disease-specific health status instrument composed of 23 items that quantify the domains of physical limitation, symptoms, self-efficacy, social limitation, and quality of life limitation due to HF. Scores range from 0 to 100. For the KCCQ overall summary score, a small but clinically meaningful change is ≥ 5 points.
Time frame: Baseline, Day 45, Day 90
Changes in Brain natriuretic peptide (BNP) levels
-B-type natriuretic peptide (BNP) will be measured at specific study visits. Differences between treatment and control arms over time will be analyzed as well as within arms over time.
Time frame: Baseline, Day 45, Day 90
Changes in the Left ventricular end-systolic volume (LVESV) and Left ventricular end-diastolic volume (LVEDV)
An echocardiogram will be performed at specific study visits and LVESV and LVEDV will be measured.
Time frame: Baseline, Day 45, Day 90
Changes Left ventricular end-systolic volume index (LVESVI) and end-diastolic volume index (LVEDVI)
An echocardiogram will be performed at specific study visits and LVESVI and LVEDVI will be measured.
Time frame: Baseline, Day 45, Day 90
Changes in the LV posterior wall (LVPW) thickness by speckle-tracking echocardiography
An echocardiogram will be performed at specific study visits where the LV posterior wall (LVPW) thickness by 2D echocardiography (longitudinal and circumferential strain and strain rate).
Time frame: Baseline, Day 45, Day 90
Changes in longitudinal and circumferential strain by speckle-tracking echocardiography
An echocardiogram will be performed at specific study visits where longitudinal and circumferential strain will be measured by 2D echocardiography (and strain rate).
Time frame: Baseline, Day 45, Day 90
Changes in the strain rate by speckle-tracking echocardiography
An echocardiogram will be performed at specific study visits where the strain rate will be measured by 2D echocardiography
Time frame: Baseline, Day 45, Day 90
Composite of all-cause mortality
The total number of subject deaths after the first week of treatment up to 12 months will be recorded
Time frame: After 1 week of study drug administration up to 12 months
Number of participants with hospital admission due to acute coronary syndrome (ACS) and all-cause HF admissions after first week
Participants will be asked about any ACS and HF hospital admission during each study visit, in addition, electronic medical records (EMR) will be reviewed periodically to document any ACS and HF hospital admission.
Time frame: After 1 week of study drug administration up to 12 months
Plan to share: No
This study is completed, as verified in Aug 2026. You cannot join it, but the record below documents what was studied.
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