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Developing Oral LT3 Therapy for Heart Failure - HFrEF (DOT3HF-HFrEF)

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ClinicalTrials.gov Identifier: NCT04112316
Recruitment Status : Recruiting
First Posted : October 2, 2019
Last Update Posted : June 11, 2020
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Anne Cappola, University of Pennsylvania

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.

Condition or disease Intervention/treatment Phase
Heart Failure With Reduced Ejection Fraction Low Triiodothyronine Syndrome Drug: liothyronine or placebo Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 28 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
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.
Primary Purpose: Treatment
Official Title: Developing Oral LT3 Therapy For Heart Failure With Reduced Ejection Fraction
Actual Study Start Date : February 11, 2020
Estimated Primary Completion Date : April 30, 2023
Estimated Study Completion Date : April 30, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Failure

Arm Intervention/treatment
Active Comparator: Liothyronine (LT3)
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.
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.

Placebo Comparator: Placebo
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.
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.




Primary Outcome Measures :
  1. Cardiac Rhythm Monitoring by 14 day Patch Rhythm Assessment [ Time Frame: continuous during intervention (14 days) ]
    Percent increase (atrial fibrillation, ventricular tachycardia, supraventricular and ventricular) ectopy

  2. T3 Level [ Time Frame: 8 weeks ]
    Percentage of participant T3 levels above upper limit of reference range


Secondary Outcome Measures :
  1. Peak Maximal Rate of Oxygen Consumption During Exercise (VO2 Max) [ Time Frame: 8 weeks ]
    Change peak rate of oxygen consumption

  2. Measure of Quality of Life [ Time Frame: 8 weeks ]
    Change in Kansas City Cardiomyopathy Questionnaire, KCCQ

  3. Actigraphy [ Time Frame: 8 weeks ]
    Change in remotely sensed difference in counts per minute (CPM)

  4. NT-proBNP levels [ Time Frame: 8 weeks ]
    Change in B-type natriuretic peptide, Pg/mL



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04112316


Contacts
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Contact: Theresa M Scattergood, MSN 215-898-5664 theresa.scattergood@pennmedicine.upenn.edu
Contact: Anne C Holland, BA 215-573-0902 anne.holland@pennmedicine.upenn.edu

Locations
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United States, Pennsylvania
PennMedicine Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Theresa M Scattergood, M.S.N., R.N.    215-898-5664    theresa.scattergood@pennmedicine.upenn.edu   
Contact: Annie C Holland, B.A.    215-573-0902    anne.holland@pennmedicine.upenn.edu   
Sponsors and Collaborators
University of Pennsylvania
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
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Principal Investigator: Anne R Cappola, MD,ScM University of Pennsylvania
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Responsible Party: Anne Cappola, Professor of Medicine, University of Pennsylvania
ClinicalTrials.gov Identifier: NCT04112316    
Other Study ID Numbers: 833681r
1R61HL146390-01 ( U.S. NIH Grant/Contract )
First Posted: October 2, 2019    Key Record Dates
Last Update Posted: June 11, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by Anne Cappola, University of Pennsylvania:
Heart Failure, HFrEF, Low T3 Syndrome
Additional relevant MeSH terms:
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Heart Failure
Heart Diseases
Cardiovascular Diseases