Developing Oral LT3 Therapy for Heart Failure - HFpEF

• Status: Recruiting
• Trial end date: 2023-04-30
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Pennsylvania
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)

Criteria

Inclusion Criteria:

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 50 percent; taking stable doses of antihypertensive medications and beta-blockers in the preceding 30 days. Elevated filling pressures as evidenced by at least 1 of the following:

1. Mitral E/e' ratio > 14 (either lateral or septal)

2. Mitral E/e' ratio > 9 (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:

1. Enlarged left atrium (LA volume index >34 ml/m2)

2. Chronic loop diuretic use for control of symptoms

3. Elevated natriuretic peptides (BNP levels >100 ng/L or NT-proBNP levels >300 ng/L)

4. Tricuspid regurgitation velocity >2.8 m/s

3. 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)

4. Acute heart failure decompensation with radiographic evidence of pulmonary venous congestion or alveolar edema, requiring IV diuretics within the past year TSH and free T4 level within the laboratory reference range and total T3 level less than 94 ng/dL; if taking oral estrogen, dose must remain stable for duration of study participation.

Exclusion Criteria:

Hypertrophic or restrictive cardiomyopathy or uncorrected severe primary valvular disease; arrhythmia that results in irregular heart rate; 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; 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 safe completion of the study.

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