Developing Oral LT3 Therapy for Heart Failure - HFrEF

Heart Failure With Reduced Ejection Fraction Clinical Trial

— DOT3HF-HFrEF  

Official title:

Developing Oral LT3 Therapy For Heart Failure With Reduced Ejection Fraction

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04112316
• Other study ID #: 833681r
• Secondary ID: 1R61HL146390-01
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: February 11, 2020
• Est. completion date: August 31, 2023

Study information

• Verified date: September 2023
• Source: University of Pennsylvania
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 triiothyronine (T3) syndrome by conducting a randomized, double-blind, placebo-controlled cross-over study with a two week washout period between treatments.

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). 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: August 31, 2023
• Est. primary completion date: August 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure With Reduced Ejection Fraction
• Low Triiodothyronine Syndrome

Intervention

Drug:
• liothyronine or placebo
Each treatment period of liothyronine or placebo will be approximately 8 weeks in duration, 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 the alternate therapy - placebo or LT3.

Locations

Country	Name	City	State
United States	PennMedicine	Philadelphia	Pennsylvania

Sponsors (2)

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

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cardiac Rhythm Monitoring by 14 day Patch Rhythm Assessment	Percent increase (atrial fibrillation, ventricular tachycardia, supraventricular and ventricular) ectopy	continuous during intervention (14 days)
Primary	T3 Level	Percentage of participant T3 levels above upper limit of reference range	8 weeks
Secondary	Peak Maximal Rate of Oxygen Consumption During Exercise (VO2 Max)	Change peak rate of oxygen consumption	8 weeks
Secondary	Measure of Quality of Life	Change in Kansas City Cardiomyopathy Questionnaire, KCCQ	8 weeks
Secondary	Actigraphy	Change in remotely sensed difference in counts per minute (CPM)	8 weeks
Secondary	NT-proBNP levels	Change in B-type natriuretic peptide, Pg/mL	8 weeks