A Phase 1/2 interventional study of Liothyronine and Placebo in Heart Failure With Reduced Ejection Fraction (HFrEF) and Low T3 Syndrome, sponsored by University of Pennsylvania. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-12-24.
Sponsored by University of Pennsylvania · Phase 1/2, Interventional, and Treatment
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.
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.
5,701 studies on the registry are indexed under Heart Failure; 1,220 are open to participants now.
This study's enrollment of 28 is below the median of 72 across 3,736 interventional studies indexed under Heart Failure.
Browse Heart Failure studies →University of Pennsylvania is the lead sponsor of 1,635 studies on the registry; 239 are open to participants now.
Of its 154 completed or terminated interventional studies of FDA-regulated products, 104 (68%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
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.
Drug: Liothyronine · Other: Placebo
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.
Drug: Liothyronine · Other: Placebo
Liothyronine (L-triiodothyronine or LT3) in the 5 mcg tablet dose formulation. Minimum LT3 dose was 2.5 mcg three times daily and the maximum LT3 dose was 12.5 mcg three times daily.
Also known as: LT3
A placebo tablet matching in appearance to LT3 tablets. Minimum placebo tablet dose was 1/2 tablet three times daily and the maximum placebo dose was 2 1/2 tablets three times daily.
Cardiac Rhythm Monitoring by 14 Day Patch Rhythm Assessment
Number of participants with atrial fibrillation or ventricular tachycardia \>= 4 beats
Time frame: continuous during intervention (14 days)
T3 Level
Number of participants with T3 levels above upper limit of reference range
Time frame: 8 weeks
Change in Peak Maximal Rate of Oxygen Consumption During Exercise (VO2 Max)
Change in peak rate of oxygen consumption during exercise between baseline and 8 weeks
Time frame: 8 weeks
Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Quality of Life
Change in KCCQ from baseline to 8 weeks, 0-100 scale, higher is better
Time frame: 8 weeks
Activity Measured Via Actigraphy
Remotely sensed minutes/day of cumulative light, moderate, or vigorous activity in minutes/day after 8 weeks of LT3 or placebo
Time frame: 8 weeks
Change in NT-proBNP Levels
Change in B-type natriuretic peptide levels, Pg/mL, from baseline to 8 weeks
Time frame: 8 weeks
| Milestone | Liothyronine (LT3), Then Placebo | Placebo, Then Liothyronine |
|---|---|---|
| Started | 14 | 14 |
| Completed | 12 | 14 |
| Not completed | 2 | 0 |
| Withdrew: Protocol violation | 1 | 0 |
| Withdrew: Lost to follow-up | 1 | 0 |
| Milestone | Liothyronine (LT3), Then Placebo | Placebo, Then Liothyronine |
|---|---|---|
| Started | 12 | 14 |
| Completed | 12 | 14 |
| Not completed | 0 | 0 |
| Milestone | Liothyronine (LT3), Then Placebo | Placebo, Then Liothyronine |
|---|---|---|
| Started | 12 | 14 |
| Completed | 12 | 14 |
| Not completed | 0 | 0 |
Number of participants with atrial fibrillation or ventricular tachycardia \>= 4 beats
| Number of participants with events | Liothyronine (LT3) | Placebo |
|---|---|---|
| Cardiac Rhythm Monitoring by 14 Day Patch Rhythm Assessment | 11 | 19 |
Number of participants with T3 levels above upper limit of reference range
| Participants | Liothyronine (LT3) | Placebo |
|---|---|---|
| T3 Level | 4 | 0 |
Change in peak rate of oxygen consumption during exercise between baseline and 8 weeks
| ml/kg/min | Liothyronine (LT3) | Placebo |
|---|---|---|
| Change in Peak Maximal Rate of Oxygen Consumption During Exercise (VO2 Max) | 11.18 ± 4.24 | 10.78 ± 4.31 |
Change in KCCQ from baseline to 8 weeks, 0-100 scale, higher is better
| units on a scale | Liothyronine (LT3) | Placebo |
|---|---|---|
| Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Quality of Life | 0.6 ± 6.8 | -0.6 ± 10.3 |
Remotely sensed minutes/day of cumulative light, moderate, or vigorous activity in minutes/day after 8 weeks of LT3 or placebo
| minutes/day | Liothyronine (LT3) | Placebo |
|---|---|---|
| Activity Measured Via Actigraphy | 241 ± 83 | 265 ± 82 |
Change in B-type natriuretic peptide levels, Pg/mL, from baseline to 8 weeks
| pg/mL | Liothyronine (LT3) | Placebo |
|---|---|---|
| Change in NT-proBNP Levels | 66.1 ± 248.3 | 98.7 ± 450.9 |
Collected over 17 weeks. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Liothyronine (LT3) | 0/28 (0%) | 0/28 (0%) | 15/28 (53.6%) |
| Placebo | 0/28 (0%) | 0/28 (0%) | 9/28 (32.1%) |
| Event | Liothyronine (LT3) | Placebo |
|---|---|---|
| TotalInvestigations | 15/28 | 9/28 |
| Age, Categorical(Participants) | Liothyronine (LT3), Then Placebo | Placebo, Then Liothyronine | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 5 | 8 | 13 |
| >=65 years | 9 | 6 | 15 |
| Age, Continuous(years) | Liothyronine (LT3), Then Placebo | Placebo, Then Liothyronine | Total |
|---|---|---|---|
| Mean | 63.9 ± 11.0 | 59.0 ± 12.3 | 61.4 ± 11.9 |
| Sex: Female, Male(Participants) | Liothyronine (LT3), Then Placebo | Placebo, Then Liothyronine | Total |
|---|---|---|---|
| Female | 2 | 4 | 6 |
| Male | 12 | 10 | 22 |
| Ethnicity (NIH/OMB)(Participants) | Liothyronine (LT3), Then Placebo | Placebo, Then Liothyronine | Total |
|---|---|---|---|
| Hispanic or Latino | 2 | 0 | 2 |
| Not Hispanic or Latino | 12 | 14 | 26 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Liothyronine (LT3), Then Placebo | Placebo, Then Liothyronine | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 2 | 4 | 6 |
| White | 12 | 10 | 22 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Region of Enrollment(participants) | Liothyronine (LT3), Then Placebo | Placebo, Then Liothyronine | Total |
|---|---|---|---|
| United States | 14 | 14 | 28 |
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