Developing Oral LT3 Therapy for Heart Failure - HFpEF

NCT04111536 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: 833681p1R61HL146390-01
• 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 preserved ejection fraction (HFpEF) 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 Preserved Ejection Fraction; Low Triiodothyronine Syndrome

Keywords

Heart Failure, HFpEF, Low T3 Syndrome

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Atrial Fibrillation or Ventricular Tachycardia >=4 Beats

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

  continuous during intervention (14 days)

• T3 Level

  Number of participant T3 levels above upper limit of reference range

  8 weeks

Secondary Outcomes (4)

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

  8 weeks

• Measure of Quality of Life

  8 weeks

• Actigraphy

  8 weeks

• NT-proBNP Levels

  8 weeks

Study Arms (2)

Liothyronine (LT3), then placebo

ACTIVE COMPARATOR

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

Drug: liothyronine; Other: Placebo

Placebo, then Liothyronine

PLACEBO COMPARATOR

A placebo tablet matching in appearance to LT3 tablets, dosed equivalently. Minimum placebo tablet dose will be 1/2 tablet (2.5 mcg equivalent) three times daily and the maximum placebo dose will be 2 1/2 tablets (12.5 mcg equivalent) three times daily.

Drug: liothyronine; Other: Placebo

Interventions

liothyronine DRUG

Each treatment period of liothyronine was approximately 8 weeks in duration, 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 the alternate therapy - placebo.

Also known as: LT3

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

Placebo OTHER

Each treatment period of placebo was approximately 8 weeks in duration, 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 the alternate therapy - LT3.

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 or dyspnea on exertion without a clinically identifiable alternative cause; left ventricular ejection fraction greater than or equal to 40 percent; if taking antihypertensive medications, beta-blockers, SGLT2inhibitors, sacubitril/valsartan, or aldosterone antagonists, doses must be stable for at least 30 days. Elevated filling pressures as evidenced by at least 1 of the following:
• Mitral E/e' ratio \> 14 (either lateral or septal)
• Mitral E/e' ratio \> 8 (either lateral or septal), with low e' velocity (septal e'\<7 cm/sec or lateral e'\< 10 cm/sec), in addition to one of the following:
• Enlarged left atrium (LA volume index \>34 ml/m2)
• Chronic loop diuretic use for control of symptoms
• Elevated natriuretic peptides (BNP levels \>100 ng/L or NT-proBNP levels \>300 ng/L)
• Tricuspid regurgitation velocity \>2.8 m/s
• Elevated invasively-determined filling pressures previously (resting LVEDP \>16 mmHg or mean pulmonary capillary wedge pressure \[PCWP\] \>12 mmHg; or PCWP/LVEDP ≥25 mmHg with exercise)
• Acute heart failure decompensation with radiographic evidence of pulmonary venous congestion or alveolar edema, requiring IV diuretics within the past year
• Probability of HFpEF\>90%according to the HFpEF score,without a more likely apparent cause for symptoms as per Investigator assessment. TSH and free T4 level within the protocol specified reference range and total T3 level less than or equal to 0.94 ng/dL; if taking oral estrogen, dose must remain stable for duration of study participation.

You may not qualify if:

• Hypertrophic or restrictive cardiomyopathy or uncorrected severe primary valvular disease; inability to perform VO2max exercise testing; severe lung disease; treatment with oral steroids within past 6 months for an exacerbation of obstructive lung disease, or the use of daytime oxygen; serum creatinine \> 3.0 mg/dL; history of cirrhosis; acute coronary syndrome or coronary artery intervention or ablation therapy within past 2 months; cardiac surgery or percutaneous valve or septal defect repair within the past 6 months; heart failure hospitalization within past month; 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; current or planned pregnancy within the timeframe of study participation; any medical condition that, in the opinion of the investigator, will interfere with safe completion of the study.

Sponsors & Collaborators

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

Study Sites (1)

Penn Medicine

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 1, 2019
• Study Start: March 8, 2020
• Primary Completion: October 31, 2023
• Study Completion: October 31, 2023
• Last Updated: January 8, 2025
• Results First Posted: January 8, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)