Developing Oral LT3 Therapy For Heart Failure With Preserved Ejection Fraction
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 28
- 试验地点
- 1
- 主要终点
- Number of Participants With Atrial Fibrillation or Ventricular Tachycardia >=4 Beats
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Participant, Investigators and Care Providers are blinded to LT3 vs. Placebo and T3 results. There will be 1 unblinded physician in the study.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Liothyronine (LT3), then placebo
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.
干预措施: liothyronine (Drug)
Liothyronine (LT3), then placebo
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.
干预措施: Placebo (Other)
Placebo, then Liothyronine
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.
干预措施: liothyronine (Drug)
Placebo, then Liothyronine
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.
干预措施: Placebo (Other)
结局指标
主要结局
Number of Participants With Atrial Fibrillation or Ventricular Tachycardia >=4 Beats
时间窗: continuous during intervention (14 days)
Number with atrial fibrillation or ventricular tachycardia \>=4 beats
T3 Level
时间窗: 8 weeks
Number of participant T3 levels above upper limit of reference range
次要结局
- 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)
研究者
Anne Cappola, MD
Professor of Medicine
University of Pennsylvania