Effects of Triiodothyronine (T3) in Ischemic Heart Failure

NCT05384847 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: STUDY00003552
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief Summary

This study aims to determine whether giving triiodothyronine (T3), a thyroid hormone, is safe and helps improve symptoms and signs of heart failure. The study is divided into 2 phases. In the first phase, participants have a 50-50 chance of receiving the study drug. 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. Participants who do not receive the drug in Phase I will have the opportunity to enroll in Phase II of the study where everyone will receive the thyroid hormone treatment. If this study finds that patients have improved heart function after treatment with thyroid hormone without unacceptable side effects, this could result in a new treatment for patients with heart failure.

Conditions

Heart Failure

Keywords

Ischemic Heart Failure; NYHA Class II-III; Implantable Cardioverter Defibrillator (ICD)

Outcome Measures

Primary Outcomes (2)

• 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.

  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

  During the first week of treatment period

Secondary Outcomes (5)

• Change in left ventricular ejection fraction (LVEF)

  Baseline, Day 45, Day 90

• Change in 6-minute walk distance (6MWD)

  Baseline, Day 45, Day 90

• Changes in New York Heart Association (NYHA) classification

  Baseline, Day 45, Day 90

• Change in Kansas City Cardiomyopathy Questionnaire (KCCQ)

  Baseline, Day 45, Day 90

• Changes in Brain natriuretic peptide (BNP) levels

  Baseline, Day 45, Day 90

Other Outcomes (7)

• Changes in the Left ventricular end-systolic volume (LVESV) and Left ventricular end-diastolic volume (LVEDV)

  Baseline, Day 45, Day 90

• Changes Left ventricular end-systolic volume index (LVESVI) and end-diastolic volume index (LVEDVI)

  Baseline, Day 45, Day 90

• Changes in the LV posterior wall (LVPW) thickness by speckle-tracking echocardiography

  Baseline, Day 45, Day 90

Study Arms (4)

Experimental Phase IA

EXPERIMENTAL

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

Experimental Phase IB

EXPERIMENTAL

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

Control Group-Phase IA and IB

PLACEBO COMPARATOR

The control group will have testing as the experimental group but will not be given any medications.

Other: Control Group

Experimental Phase II

EXPERIMENTAL

Patients who were enrolled in the open-label control group of Phase I and who have completed the 3-month follow-up will be permitted to enroll in Phase II. This Phase will start treatment after completion of Phase I and approval from the Data and Safety Monitoring Board (DSMB) to proceed with a single cohort that will receive a stable dose of the study drug (20 µg T3 orally twice daily for 5 days).

Drug: Thyroid hormone T3

Interventions

Thyroid hormone T3 DRUG

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

Experimental Phase IA; Experimental Phase IB; Experimental Phase II

Control Group OTHER

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

Control Group-Phase IA and IB

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18-80 years, male or female;
• Confirmed diagnosis of ischemic HF with left ventricular ejection fraction (LVEF) ≤ 40% (measured by echocardiography within 1 month of Screening);
• Stable symptoms; NYHA class II-III without recent admission (1 month) for acute decompensation;
• Receiving guideline-based standard HF therapies at the maximum tolerated doses for \>1 month. Patients on other beta-blockers will be switched to metoprolol succinate at equivalent doses for 3 weeks.
• Presence of ICD for \>1 month or implantable cardiac resynchronization therapy defibrillator (CRT-D) for \>3 months
• Understand and sign the informed consent form.

You may not qualify if:

• LVEF \> 40%;
• Unremitting atrial fibrillation during the screening period or clinically significant ventricular tachycardia (on ICD interrogation);
• Non-ischemic HF including hypertrophic cardiomyopathy, peripartum or chemotherapy-induced cardiomyopathy, other non-ischemic cardiomyopathies, constrictive pericarditis, significant and uncorrected valvular heart disease (severe regurgitation or severe stenosis or valvular disease requiring surgery), congenital heart disease, primary pulmonary hypertension or secondary severe pulmonary hypertension (≥ 70 mmHg); large pericardial or pleural effusions; right heart failure due to lung disease;
• Recent admission (1 month) for acute decompensated HF;
• Angina pectoris, cerebrovascular accident, myocardial infarction, revascularization (PCI or other surgery), carotid artery or other large vessel surgery, or cardiac resynchronization therapy (CRT) implant within the past 3 months;
• Planned revascularization within 6 months;
• History of heart transplantation, use of ventricular assist device (VAD) or preparation for heart transplantation, VAD;
• Liver dysfunction (bilirubin or alkaline phosphatase \> 2 times the upper limit of normal (ULN), aspartate aminotransferase or alanine aminotransferase \> 3 times the upper limit of normal), estimated glomerular filtration rate (eGFR) calculated using the Modification of Diet in Renal Disease Study (MDRD) method \< 30 ml/min/1.73 m2;
• Systolic blood pressure \< 90 mmHg or \> 160 mmHg;
• Blood K+ \< 3.2 mmol/L or \> 5.5 mmol/L;
• Women of childbearing age who are planning to become pregnant within 2 years, and pregnant or lactating women;
• Patients whose survival time is expected to be less than 6 months as judged by the investigator;
• Those who have participated in any drug clinical trial within the previous 3 months;
• Severe neurological disorders (Alzheimer's disease, progressive parkinsonism);
• The subjects with a history of cancer that limits life expectancy to \<1 year;

Sponsors & Collaborators

• Emory University: lead

Study Sites (2)

Emory University Hospital (EUH)

Atlanta, Georgia, 30322, United States

Location

Emory University Hospital Clinical Research Network

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Conditions

Heart Failure

Interventions

Triiodothyronine; Control Groups

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Thyronines; Thyroid Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Thyroxine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Research Design; Methods

Study Officials

• Arshed A. Quyyumi, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: April 29, 2022
• First Posted: May 20, 2022
• Study Start: December 2, 2022
• Primary Completion: May 1, 2026
• Study Completion: May 1, 2026
• Last Updated: June 26, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)