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| ID | Type | Description | Link |
|---|---|---|---|
| 1R61HL146390-01 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Liothyronine (LT3), then placebo | Active Comparator | 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. |
|
| Placebo, then liothyronine | Placebo Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Liothyronine | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Cardiac Rhythm Monitoring by 14 Day Patch Rhythm Assessment | Number of participants with atrial fibrillation or ventricular tachycardia >= 4 beats | continuous during intervention (14 days) |
| T3 Level | Number of participants with T3 levels above upper limit of reference range | 8 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 8 weeks |
| Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Quality of Life |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Anne R Cappola, MD,ScM | University of Pennsylvania | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| PennMedicine | Philadelphia | Pennsylvania | 19104 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. Liothyronine: 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. Placebo: 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. |
| FG001 | 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. Liothyronine: 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. Placebo: 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Period (8 Weeks) |
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| Washout (2 Weeks) |
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| Second Intervention (8 Weeks) |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. Liothyronine: 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. Placebo: 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Cardiac Rhythm Monitoring by 14 Day Patch Rhythm Assessment | Number of participants with atrial fibrillation or ventricular tachycardia >= 4 beats | Posted | Number | Number of participants with events | continuous during intervention (14 days) |
|
17 weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Liothyronine (LT3) | Participants who received liothyronine for the first 8 weeks or the last 8 weeks of the study. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Total | Investigations | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Theresa M Scattergood, MSN | University of Pennsylvania | 215-898-5664 | theresa.scattergood@pennmedicine.upenn.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | May 11, 2022 | Aug 27, 2024 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D005067 | Euthyroid Sick Syndromes |
| D006333 | Heart Failure |
| ID | Term |
|---|---|
| D013959 | Thyroid Diseases |
| D004700 | Endocrine System Diseases |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D014284 | Triiodothyronine |
| ID | Term |
|---|---|
| D013970 | Thyronines |
| D013963 | Thyroid Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
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Participant, Investigators and Care Providers are blinded to LT3 vs. Placebo and T3 results. There will be 1 unblinded physician in the study.
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| Placebo | Other | 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. |
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Change in KCCQ from baseline to 8 weeks, 0-100 scale, higher is better
| 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 | 8 weeks |
| Change in NT-proBNP Levels | Change in B-type natriuretic peptide levels, Pg/mL, from baseline to 8 weeks | 8 weeks |
| NOT COMPLETED |
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| NOT COMPLETED |
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| BG001 | 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. Liothyronine: 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. Placebo: 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. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Units | Counts |
|---|
| Participants |
|
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| Primary | T3 Level | Number of participants with T3 levels above upper limit of reference range | Posted | Count of Participants | Participants | 8 weeks |
|
|
|
| Secondary | 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 | Posted | Mean | Standard Deviation | ml/kg/min | 8 weeks |
|
|
|
| Secondary | Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Quality of Life | Change in KCCQ from baseline to 8 weeks, 0-100 scale, higher is better | Posted | Mean | Standard Deviation | units on a scale | 8 weeks |
|
|
|
| Secondary | 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 | Posted | Mean | Standard Deviation | minutes/day | 8 weeks |
|
|
|
| Secondary | Change in NT-proBNP Levels | Change in B-type natriuretic peptide levels, Pg/mL, from baseline to 8 weeks | Posted | Mean | Standard Deviation | pg/mL | 8 weeks |
|
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|
| 0 |
| 28 |
| 0 |
| 28 |
| 15 |
| 28 |
| EG001 | Placebo | Participants who received placebo for the first 8 weeks or the last 8 weeks of the study. | 0 | 28 | 0 | 28 | 9 | 28 |
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| D013974 | Thyroxine |
| D024322 | Amino Acids, Aromatic |
| D000598 | Amino Acids, Cyclic |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |