Heart Failure With Reduced Ejection Fraction (HFrEF)Phase 1/2DOT3HF-HFrEFNCT04112316
Developing Oral LT3 Therapy for Heart Failure - HFrEF
A Phase 1/2 study testing Liothyronine in people with Heart Failure With Reduced Ejection Fraction (HFrEF) and Low T3 Syndrome, run by University of Pennsylvania at 1 site in United States.
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 triiodothyronine (T3) syndrome by conducting a randomized, double-blind, placebo-controlled cross-over study with a… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure With Reduced Ejection Fraction (HFrEF), Low T3 Syndrome
- What is being tested?
- Liothyronine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 28 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Feb 2020to 31 Oct 2023
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Developing Oral LT3 Therapy For Heart Failure With Reduced Ejection Fraction
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.
Read the 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.
- Being tested
- Liothyronine, Placebo
- Keywords
- Heart Failure, HFrEF, Low T3 Syndrome
- Medical subject headings
- Euthyroid Sick Syndromes, Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LiothyronineDrug
Also called LT3
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.
PlaceboOther
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Liothyronine; Other: Placebo |
| 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. Receives: Drug: Liothyronine; Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cardiac Rhythm Monitoring by 14 Day Patch Rhythm Assessment
Number of participants with atrial fibrillation or ventricular tachycardia >= 4 beats
Measured: continuous during intervention (14 days)
T3 Level
Number of participants with T3 levels above upper limit of reference range
Measured: 8 weeks
Secondary outcomes (4)
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
Measured: 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
Measured: 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
Measured: 8 weeks
Change in NT-proBNP Levels
Change in B-type natriuretic peptide levels, Pg/mL, from baseline to 8 weeks
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Oct 2019
- Study start11 Feb 2020
- Primary completion31 Oct 2023
- Study completion31 Oct 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Heart Failure With Reduced Ejection Fraction (HFrEF)Studies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Anne Cappola, MD, University of Pennsylvania
- Investigators
- Anne R Cappola, MD,ScM, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04112316
- Sponsor's protocol ID
- 833681r
- Other IDs
- 1R61HL146390-01
- Acronym
- DOT3HF-HFrEF
- Status last verified
- Dec 2024
- First submitted
- 30 Sep 2019
- Last updated
- 24 Dec 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Developing Oral LT3 Therapy For Heart Failure With Reduced Ejection Fraction
- ClinicalTrials.gov ID
- NCT04112316
- Acronym / sponsor ID
- DOT3HF-HFrEF / 833681r
- Keywords
- Heart Failure, HFrEF, Low T3 Syndrome
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 11 Feb 2020 (actual)
- Primary completion
- 31 Oct 2023 (actual)
- Study completion
- 31 Oct 2023 (actual)
- First posted
- 2 Oct 2019 (actual)
- Results
- Posted 24 Dec 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Liothyronine (LT3), then placebo | Active comparator | Drug: Liothyronine, Other: PlaceboParticipants 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 | Drug: Liothyronine, Other: PlaceboParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LiothyronineAlso: LT3Liothyronine (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. | Drug | Liothyronine (LT3), then placebo, Placebo, then liothyronine |
| PlaceboA 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. | Other | Liothyronine (LT3), then placebo, Placebo, then liothyronine |
Primary outcome
Cardiac Rhythm Monitoring by 14 Day Patch Rhythm Assessment
Time frame: continuous during intervention (14 days)
Number of participants with atrial fibrillation or ventricular tachycardia >= 4 beats
T3 Level
Time frame: 8 weeks
Number of participants with T3 levels above upper limit of reference range
4 secondary outcomes
Change in Peak Maximal Rate of Oxygen Consumption During Exercise (VO2 Max)
Time frame: 8 weeks
Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Quality of Life
Time frame: 8 weeks
Activity Measured Via Actigraphy
Time frame: 8 weeks
Change in NT-proBNP Levels
Time frame: 8 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Dec 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anne R Cappola, MD,ScM principal investigator
University of Pennsylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Liothyronine in people with Heart Failure With Reduced Ejection Fraction (HFrEF) and Low T3 Syndrome, run by University of Pennsylvania at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cardiac Rhythm Monitoring by 14 Day Patch Rhythm Assessment (time frame: continuous during intervention (14 days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Dec 2024.