Back to resultsDeveloping Oral LT3 Therapy for Heart Failure - HFrEF (DOT3HF-HFrEF)
Primary Purpose
Heart Failure With Reduced Ejection Fraction, Low Triiodothyronine Syndrome
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
liothyronine or placebo
Sponsored by
About this trial
This is an interventional treatment trial for Heart Failure With Reduced Ejection Fraction focused on measuring Heart Failure, HFrEF, Low T3 Syndrome
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
- LVAD use
- 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.
Sites / Locations
- PennMedicine
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Liothyronine (LT3)
Placebo
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Cardiac Rhythm Monitoring by 14 day Patch Rhythm Assessment
Percent increase (atrial fibrillation, ventricular tachycardia, supraventricular and ventricular) ectopy
T3 Level
Percentage of participant T3 levels above upper limit of reference range
Secondary Outcome Measures
Peak Maximal Rate of Oxygen Consumption During Exercise (VO2 Max)
Change peak rate of oxygen consumption
Measure of Quality of Life
Change in Kansas City Cardiomyopathy Questionnaire, KCCQ
Actigraphy
Change in remotely sensed difference in counts per minute (CPM)
NT-proBNP levels
Change in B-type natriuretic peptide, Pg/mL
Full Information
NCT ID
NCT04112316
First Posted
September 30, 2019
Last Updated
September 22, 2023
Sponsor
University of Pennsylvania
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
1. Study Identification
Unique Protocol Identification Number
NCT04112316
Brief Title
Developing Oral LT3 Therapy for Heart Failure - HFrEF
Acronym
DOT3HF-HFrEF
Official Title
Developing Oral LT3 Therapy For Heart Failure With Reduced Ejection Fraction
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Completed
Study Start Date
February 11, 2020 (Actual)
Primary Completion Date
August 31, 2023 (Actual)
Study Completion Date
August 31, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Pennsylvania
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
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 triiothyronine (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). 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure With Reduced Ejection Fraction, Low Triiodothyronine Syndrome
Keywords
Heart Failure, HFrEF, Low T3 Syndrome
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigator
Masking Description
Participant, Investigators and Care Providers are blinded to LT3 vs. Placebo and T3 results. There will be 1 unblinded physician in the study.
Allocation
Randomized
Enrollment
28 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Liothyronine (LT3)
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
liothyronine or placebo
Intervention Description
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.
Primary Outcome Measure Information:
Title
Cardiac Rhythm Monitoring by 14 day Patch Rhythm Assessment
Description
Percent increase (atrial fibrillation, ventricular tachycardia, supraventricular and ventricular) ectopy
Time Frame
continuous during intervention (14 days)
Title
T3 Level
Description
Percentage of participant T3 levels above upper limit of reference range
Time Frame
8 weeks
Secondary Outcome Measure Information:
Title
Peak Maximal Rate of Oxygen Consumption During Exercise (VO2 Max)
Description
Change peak rate of oxygen consumption
Time Frame
8 weeks
Title
Measure of Quality of Life
Description
Change in Kansas City Cardiomyopathy Questionnaire, KCCQ
Time Frame
8 weeks
Title
Actigraphy
Description
Change in remotely sensed difference in counts per minute (CPM)
Time Frame
8 weeks
Title
NT-proBNP levels
Description
Change in B-type natriuretic peptide, Pg/mL
Time Frame
8 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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
LVAD use
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anne R Cappola, MD,ScM
Organizational Affiliation
University of Pennsylvania
Official's Role
Principal Investigator
Facility Information:
Facility Name
PennMedicine
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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Developing Oral LT3 Therapy for Heart Failure - HFrEF
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