Clinical trial NCT04112316: Developing Oral LT3 Therapy for Heart Failure - HFrEF
Official title: Developing Oral LT3 Therapy For Heart Failure With Reduced Ejection Fraction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Heart Failure With Reduced Ejection Fraction (HFrEF)
Low T3 Syndrome
Keywords: Heart Failure
HFrEF
Low T3 Syndrome
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2019-10-02
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 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.

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 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.

Eligibility criteria: Inclusion Criteria:

1. Men and women aged ≥18 years
2. NYHA Class I, II or III heart failure
3. EF≤40 percent within the past year
4. An implantable cardioverter-defibrillator (ICD)
5. Stable doses of neurohormonal blockade for 30 days
6. TSH and free T4 level within the laboratory reference range and total T3 level \<94 ng/dL

Exclusion Criteria:

1. Hypertrophic or restrictive cardiomyopathy
2. Uncorrected severe primary valvular disease
3. Arrhythmia that results in irregular heart rate
4. Inability to perform VO2max exercise testing
5. Severe lung disease, including treatment with oral steroids within past 6 months for exacerbation of obstructive lung disease or use of daytime supplemental oxygen
6. Serum creatinine \> 3.0 mg/dL
7. History of cirrhosis
8. LVAD use
9. Heart failure hospitalization within past month
10. 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
11. 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
12. If female, current or planned pregnancy within the timeframe of study participation
13. Any medical condition that in the opinion of the investigator, will interfere with the safe completion of the study.

Primary outcomes:
measure: Cardiac Rhythm Monitoring by 14 Day Patch Rhythm Assessment
timeFrame: continuous during intervention (14 days)
measure: T3 Level
timeFrame: 8 weeks
Secondary outcomes:
measure: Change in Peak Maximal Rate of Oxygen Consumption During Exercise (VO2 Max)
timeFrame: 8 weeks
measure: Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Quality of Life
timeFrame: 8 weeks
measure: Activity Measured Via Actigraphy
timeFrame: 8 weeks
measure: Change in NT-proBNP Levels
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: PennMedicine
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania
name: Anne R Cappola, MD,ScM
role: PRINCIPAL_INVESTIGATOR
References: