Developing Oral LT3 Therapy for Heart Failure - HFrEF

NCT04112316 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: 833681r1R61HL146390-01
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

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

Keywords

Heart Failure; HFrEF; Low T3 Syndrome

Outcome Measures

Primary Outcomes (2)

• Cardiac Rhythm Monitoring by 14 Day Patch Rhythm Assessment

  Number of participants with atrial fibrillation or ventricular tachycardia \>= 4 beats

  continuous during intervention (14 days)

• T3 Level

  Number of participants with T3 levels above upper limit of reference range

  8 weeks

Secondary Outcomes (4)

• Change in Peak Maximal Rate of Oxygen Consumption During Exercise (VO2 Max)

  8 weeks

• Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Quality of Life

  8 weeks

• Activity Measured Via Actigraphy

  8 weeks

• Change in NT-proBNP Levels

  8 weeks

Study Arms (2)

Liothyronine (LT3), then placebo

ACTIVE COMPARATOR

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.

Drug: Liothyronine; Other: Placebo

Placebo, then liothyronine

PLACEBO COMPARATOR

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.

Drug: Liothyronine; Other: Placebo

Interventions

Liothyronine 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.

Also known as: LT3

Liothyronine (LT3), then placebo; Placebo, then liothyronine

Placebo 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.

Liothyronine (LT3), then placebo; Placebo, then liothyronine

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

• Hypertrophic or restrictive cardiomyopathy
• Uncorrected severe primary valvular disease
• Arrhythmia that results in irregular heart rate
• Inability to perform VO2max exercise testing
• Severe lung disease, including treatment with oral steroids within past 6 months for exacerbation of obstructive lung disease or use of daytime supplemental oxygen
• Serum creatinine \> 3.0 mg/dL
• History of cirrhosis
• LVAD use
• Heart failure hospitalization within past month
• 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
• 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
• If female, current or planned pregnancy within the timeframe of study participation
• Any medical condition that in the opinion of the investigator, will interfere with the safe completion of the study.

Sponsors & Collaborators

• University of Pennsylvania: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

PennMedicine

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Euthyroid Sick Syndromes; Heart Failure

Interventions

Triiodothyronine

Condition Hierarchy (Ancestors)

Thyroid Diseases; Endocrine System Diseases; 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

Results Point of Contact

• Title: Theresa M Scattergood, MSN
• Organization: University of Pennsylvania

theresa.scattergood@pennmedicine.upenn.edu

215-898-5664

Study Officials

• Anne R Cappola, MD,ScM

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Participant, Investigators and Care Providers are blinded to LT3 vs. Placebo and T3 results. There will be 1 unblinded physician in the study.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: September 30, 2019
• First Posted: October 2, 2019
• Study Start: February 11, 2020
• Primary Completion: October 31, 2023
• Study Completion: October 31, 2023
• Last Updated: December 24, 2024
• Results First Posted: December 24, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)