Clinical trial NCT04111536: Developing Oral LT3 Therapy for Heart Failure - HFpEF
Official title: Developing Oral LT3 Therapy For Heart Failure With Preserved Ejection Fraction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Heart Failure With Preserved Ejection Fraction
Low Triiodothyronine Syndrome
Keywords: Heart Failure, HFpEF, Low T3 Syndrome
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2019-10-01
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Detailed description: 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 preserved ejection fraction (HFpEF). 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.

Eligibility 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 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:

1. Mitral E/e' ratio \> 14 (either lateral or septal)
2. 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:

   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
5. 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.

Exclusion Criteria:

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.

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Primary outcomes:
measure: Number of Participants With Atrial Fibrillation or Ventricular Tachycardia >=4 Beats
timeFrame: continuous during intervention (14 days)
measure: T3 Level
timeFrame: 8 weeks
Secondary outcomes:
measure: Peak Maximal Rate of Oxygen Consumption During Exercise (VO2 Max)
timeFrame: 8 weeks
measure: Measure of Quality of Life
timeFrame: 8 weeks
measure: Actigraphy
timeFrame: 8 weeks
measure: NT-proBNP Levels
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Penn Medicine
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania
name: Anne R Cappola, MD,ScM
role: PRINCIPAL_INVESTIGATOR
References: