Developing Oral LT3 Therapy for Heart Failure - HFrEF

NCT ID: NCT04112316

Last Updated: 2024-12-24

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

28 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-02-11

Study Completion Date

2023-10-31

Brief Summary

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Investigation of the safety, feasibility, and preliminary efficacy of thyroid hormone therapy with Liothyronine (LT3) in individuals with heart failure with reduced ejection fraction (HFrEF) and low triiodothyronine (T3) syndrome by conducting a randomized, double-blind, placebo-controlled cross-over study with a two-week washout period between treatments.

Detailed Description

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The overall goal is to determine the safety, feasibility, and preliminary efficacy of administering oral LT3 therapy in the study population of participants with Heart Failure with reduced ejection fraction (HFrEF). The study will consist of two treatment periods - each treatment period will be approximately 8 weeks in duration, with weekly titration of study drug for 4 weeks, followed by a maintenance dose for 4 weeks, then 2-week washout before crossing over to the other arm (placebo or drug). LT3 will be titrated to T3 levels.

Conditions

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Heart Failure With Reduced Ejection Fraction (HFrEF) Low T3 Syndrome

Keywords

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Heart Failure HFrEF Low T3 Syndrome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators
Participant, Investigators and Care Providers are blinded to LT3 vs. Placebo and T3 results. There will be 1 unblinded physician in the study.

Study Groups

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Liothyronine (LT3), then placebo

Participants received liothyronine first, with weekly titration of study drug for four weeks, followed by a maintenance dose for 4 weeks, then 2-week washout before crossing over to receive placebo for 8 weeks.

Group Type ACTIVE_COMPARATOR

Liothyronine

Intervention Type DRUG

Liothyronine (L-triiodothyronine or LT3) in the 5 mcg tablet dose formulation. Minimum LT3 dose was 2.5 mcg three times daily and the maximum LT3 dose was 12.5 mcg three times daily.

Placebo

Intervention Type OTHER

A placebo tablet matching in appearance to LT3 tablets. Minimum placebo tablet dose was 1/2 tablet three times daily and the maximum placebo dose was 2 1/2 tablets three times daily.

Placebo, then liothyronine

Participants received placebo first, with weekly sham titration for four weeks, followed by a maintenance dose for 4 weeks, then 2-week washout before crossing over to receive LT3 for 8 weeks.

Group Type PLACEBO_COMPARATOR

Liothyronine

Intervention Type DRUG

Liothyronine (L-triiodothyronine or LT3) in the 5 mcg tablet dose formulation. Minimum LT3 dose was 2.5 mcg three times daily and the maximum LT3 dose was 12.5 mcg three times daily.

Placebo

Intervention Type OTHER

A placebo tablet matching in appearance to LT3 tablets. Minimum placebo tablet dose was 1/2 tablet three times daily and the maximum placebo dose was 2 1/2 tablets three times daily.

Interventions

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Liothyronine

Liothyronine (L-triiodothyronine or LT3) in the 5 mcg tablet dose formulation. Minimum LT3 dose was 2.5 mcg three times daily and the maximum LT3 dose was 12.5 mcg three times daily.

Intervention Type DRUG

Placebo

A placebo tablet matching in appearance to LT3 tablets. Minimum placebo tablet dose was 1/2 tablet three times daily and the maximum placebo dose was 2 1/2 tablets three times daily.

Intervention Type OTHER

Other Intervention Names

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LT3

Eligibility Criteria

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Inclusion Criteria

1. Men and women aged ≥18 years
2. NYHA Class I, II or III heart failure
3. EF≤40 percent within the past year
4. An implantable cardioverter-defibrillator (ICD)
5. Stable doses of neurohormonal blockade for 30 days
6. TSH and free T4 level within the laboratory reference range and total T3 level \<94 ng/dL

Exclusion Criteria

1. Hypertrophic or restrictive cardiomyopathy
2. Uncorrected severe primary valvular disease
3. Arrhythmia that results in irregular heart rate
4. Inability to perform VO2max exercise testing
5. Severe lung disease, including treatment with oral steroids within past 6 months for exacerbation of obstructive lung disease or use of daytime supplemental oxygen
6. Serum creatinine \> 3.0 mg/dL
7. History of cirrhosis
8. LVAD use
9. Heart failure hospitalization within past month
10. Acute coronary syndrome, coronary intervention or ablation therapy within past 2 months or cardiac surgery, percutaneous repair of a valve or septal defect repair within the past 6 months
11. Taking thyroid extract, LT4, LT3, amiodarone, or medication that affects the absorption or metabolism of thyroid hormone; gastrointestinal conditions that affect the absorption of thyroid hormone
12. If female, current or planned pregnancy within the timeframe of study participation
13. Any medical condition that in the opinion of the investigator, will interfere with the safe completion of the study.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

University of Pennsylvania

OTHER

Sponsor Role lead

Responsible Party

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Anne Cappola, MD

Professor of Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Anne R Cappola, MD,ScM

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Locations

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PennMedicine

Philadelphia, Pennsylvania, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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1R61HL146390-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

833681r

Identifier Type: -

Identifier Source: org_study_id