Developing Oral LT3 Therapy For Heart Failure With Reduced 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
- Cardiac Rhythm Monitoring by 14 Day Patch Rhythm Assessment
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 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.
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 reduced ejection fraction (HFrEF). 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
- •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
排除标准
- •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
- •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.
研究组 & 干预措施
Liothyronine (LT3), then placebo
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.
干预措施: Liothyronine (Drug)
Liothyronine (LT3), then placebo
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.
干预措施: Placebo (Other)
Placebo, then liothyronine
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.
干预措施: Liothyronine (Drug)
Placebo, then liothyronine
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.
干预措施: Placebo (Other)
结局指标
主要结局
Cardiac Rhythm Monitoring by 14 Day Patch Rhythm Assessment
时间窗: continuous during intervention (14 days)
Number of participants with atrial fibrillation or ventricular tachycardia \>= 4 beats
T3 Level
时间窗: 8 weeks
Number of participants with T3 levels above upper limit of reference range
次要结局
- 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)
研究者
Anne Cappola, MD
Professor of Medicine
University of Pennsylvania