20 Participants Needed

Triiodothyronine (T3) for Heart Failure

Recruiting at 1 trial location
AA
Overseen ByArshed A. Quyyumi, MD
Age: 18+
Sex: Any
Trial Phase: Phase 1 & 2
Sponsor: Emory University
Must be taking: Metoprolol succinate
Approved in 2 JurisdictionsThis treatment is already approved in other countries

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it mentions that patients on other beta-blockers will be switched to metoprolol succinate for 3 weeks. It's best to discuss your specific medications with the study team.

What evidence supports the effectiveness of the drug Triiodothyronine (T3) for heart failure?

Research suggests that Triiodothyronine (T3) may improve heart function in patients with heart conditions, as studies have shown it can enhance heart performance and reduce heart damage in patients with heart attacks. However, more research is needed to confirm its benefits specifically for heart failure.12345

Is Triiodothyronine (T3) generally safe for use in humans?

Triiodothyronine (T3) has been studied for various conditions, and while low doses are generally well-tolerated, higher doses can increase heart rate and the risk of heart rhythm problems and sudden death. Long-term use of T3 has been associated with increased risks of heart failure and stroke, especially in patients with a history of thyroid cancer.16789

How does the drug Triiodothyronine (T3) differ from other treatments for heart failure?

Triiodothyronine (T3) is unique in treating heart failure because it targets low levels of T3, a thyroid hormone often reduced in heart failure patients, to improve heart function and metabolism. Unlike standard heart failure treatments, T3 specifically addresses thyroid hormone imbalances, which can enhance cardiac performance and potentially improve survival rates.168910

Research Team

AA

Arshed A. Quyyumi, MD

Principal Investigator

Emory University

Eligibility Criteria

This trial is for adults aged 18-80 with ischemic heart failure and a left ventricular ejection fraction (LVEF) ≤ 40%. They must be stable, on standard heart failure therapies including metoprolol succinate, and have an ICD or CRT-D device. Excluded are those with recent cardiac events, other drug trials within 3 months, endocrine disorders like thyroid disease, severe blood pressure issues, liver or kidney dysfunction, severe neurological disorders, life-limiting cancer history or planning major surgery.

Inclusion Criteria

Presence of ICD for >1 month or implantable cardiac resynchronization therapy defibrillator (CRT-D) for >3 months
My heart's pumping ability is reduced (LVEF ≤ 40%).
I am between 18 and 80 years old.
See 3 more

Exclusion Criteria

Those who have participated in any drug clinical trial within the previous 3 months
LVEF > 40%
I have ongoing atrial fibrillation or serious ventricular tachycardia.
See 16 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase IA Treatment

Participants receive ascending doses of T3 (5 µg orally twice daily for the first 2 days and 10 µg orally twice daily for the next 3 days) with monitoring

5 days
5 visits (in-person at GCRC)

Phase IB Treatment

Participants receive adjusted doses of T3 (10 µg orally twice daily on day 1 and 20 µg twice daily from day 2 to 5) based on safety data

5 days
5 visits (in-person at GCRC)

Phase II Treatment

Participants receive a stable dose of T3 (20 µg orally twice daily for 5 days) after completing Phase I

5 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months
4 visits (in-person)

Treatment Details

Interventions

  • Triiodothyronine (T3)
Trial OverviewThe study tests if Triiodothyronine (T3), a thyroid hormone can safely improve symptoms of ischemic heart failure. Participants have equal chances to receive T3 or no treatment initially; non-treated in Phase 1 may get T3 in Phase 2. The first group stays at the GCRC for monitoring over five days plus follow-ups; the second has outpatient visits.
Participant Groups
4Treatment groups
Experimental Treatment
Placebo Group
Group I: Experimental Phase IIExperimental Treatment1 Intervention
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).
Group II: Experimental Phase IBExperimental Treatment1 Intervention
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.
Group III: Experimental Phase IAExperimental Treatment1 Intervention
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).
Group IV: Control Group-Phase IA and IBPlacebo Group1 Intervention
The control group will have testing as the experimental group but will not be given any medications.

Triiodothyronine (T3) is already approved in European Union, United States for the following indications:

🇪🇺
Approved in European Union as Liothyronine for:
  • Hypothyroidism
  • Heart failure with low-T3 syndrome
🇺🇸
Approved in United States as Liothyronine for:
  • Hypothyroidism
  • Heart failure with low-T3 syndrome

Find a Clinic Near You

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials
1,735
Recruited
2,605,000+

Findings from Research

In a study of 133 heart failure patients, low plasma levels of triiodothyronine (T3) were linked to more severe heart failure symptoms, including older age, lower functional capacity, and higher levels of NT-proBNP, a marker of heart stress.
The lowest T3 levels were also associated with unfavorable hormonal and metabolic changes, such as lower DHEAS levels and worse renal function, suggesting that T3 may play a critical role in the overall health of heart failure patients.
Low plasma triiodothyronine levels in heart failure are associated with a reduced anabolic state and membrane damage.Brenta, G., Thierer, J., Sutton, M., et al.[2016]
In a study of 737 patients with acute first-ever stroke, 56% had low triiodothyronine (T3) levels, which were associated with a higher 1-year mortality rate of 27.34% compared to 19.37% for those with normal T3 levels.
Low T3 levels were also linked to a lower likelihood of independence after one year, with only 54.2% of low T3 patients achieving independence compared to 68.7% of those with normal T3, indicating that low T3 is a significant predictor of both survival and functional outcomes post-stroke.
Low triiodothyronine: a strong predictor of outcome in acute stroke patients.Alevizaki, M., Synetou, M., Xynos, K., et al.[2022]
Low triiodothyronine syndrome (LT3S) occurs in 23.3% of patients with acute myocardial infarction (AMI) and is associated with more severe myocardial injury, as indicated by higher levels of cardiac troponin I and N-terminal pro-brain natriuretic peptide.
Patients with LT3S have a significantly higher rate of in-hospital cardiovascular death (4.7% vs. 1.7%) compared to those without LT3S, and incorporating LT3S into the TIMI risk score improves the predictive accuracy for in-hospital cardiovascular death.
Low T3 syndrome improves risk prediction of in-hospital cardiovascular death in patients with acute myocardial infarction.Su, W., Zhao, XQ., Wang, M., et al.[2019]

References

Low plasma triiodothyronine levels in heart failure are associated with a reduced anabolic state and membrane damage. [2016]
Low triiodothyronine: a strong predictor of outcome in acute stroke patients. [2022]
Low T3 syndrome improves risk prediction of in-hospital cardiovascular death in patients with acute myocardial infarction. [2019]
Effects of Acute Triiodothyronine Treatment in Patients with Anterior Myocardial Infarction Undergoing Primary Angioplasty: Evidence from a Pilot Randomized Clinical Trial (ThyRepair Study). [2022]
Usefulness of Triiodothyronine Replacement Therapy in Patients With ST Elevation Myocardial Infarction and Borderline/Reduced Triiodothyronine Levels (from the THIRST Study). [2019]
Effects of Triiodothyronine Treatment in an Animal Model of Heart Failure with Preserved Ejection Fraction. [2023]
Heart Failure and Stroke Risks in Users of Liothyronine With or Without Levothyroxine Compared with Levothyroxine Alone: A Propensity Score-Matched Analysis. [2022]
Effect of short-term infusive dobutamine therapy on thyroid hormone profile and hemodynamic parameters in patients with acute worsening heart failure and low-triiodothyronine syndrome. [2016]
Effects of triiodothyronine replacement therapy in patients with chronic stable heart failure and low-triiodothyronine syndrome: a randomized, double-blind, placebo-controlled study. [2021]
10.United Statespubmed.ncbi.nlm.nih.gov
Thyroid hormone abnormalities in heart failure: possibilities for therapy. [2022]