A Thyroid Hormone Analog to Fight Heart Failure: Phase II Trial (DITPA)
A Thyroid Hormone Analog to Fight Heart Failure: Phase II Trial (DITPA)
Congestive heart failure (CHF) affects 4-5 million Americans, and its prevalence is predicted
 to increase over the next few decades. Thyroid hormone has unique actions which make it a
 novel and potentially useful agent for treatment of CHF. Due to possible adverse affects of
 thyroid hormone, there is interest in developing analogs with fewer undesirable side effects.
 3,5- diiodothyropropionic acid (DITPA) has been shown to improve diastolic function in both
 animal models and a recently completed double-blind placebo controlled trial in 19 humans.

 The goal of the proposed Phase II study is to show safety and demonstrate a medication of
 efficacy of DITPA needed in patients with CHF. This study is a prerequisite for a larger
 Phase III trial which would determine whether mortality is improved with DITPA. To better
 define the appropriate doses, prior to the Phase II study we will conduct an initial
 pharmacokinetic study.
Intervention: After enrollment, patients receive a clinical assessment, echocardiogram and
 laboratory studies. Then, each patient receives treatment with one of two doses of
 3,5-diiodothyropropionic acid (DITPA) or placebo for six months.

 Primary hypothesis: DITPA will improve cardiovascular function and clinical status in
 patients with moderately severe heart failure and be similar to placebo on safety measures.

 Secondary hypothesis:

 Primary Outcomes: 1. Composite endpoint composed of cardiovascular mortality/morbidity,
 change in NYHA class and change in global assessment, and 2. safety.

 Study Abstract: Congestive heart failure (CHF) affects 4-5 million Americans, and its
 prevalence is predicted to increase over the next few decades. Thyroid hormone has unique
 actions which make it a novel and potentially useful agent for treatment of CHF. Due to
 possible adverse effects of thyroid hormone, there is interest in developing analogs with
 fewer undesirable side effects. DITPA has been shown to improve diastolic function in both
 animal models and a recently completed double-blind placebo controlled trial in 19 humans.

 The goal of the proposed Phase II study is to define the dose of DITPA needed to achieve
 hemodynamic improvement in patients with CHF. This study is a prerequisite for a larger Phase
 III trial which would determine whether mortality is improved with DITPA. To better define
 the appropriate doses, prior to the Phase II study we will conduct an initial pharmacokinetic
 study.
Inclusion Criteria:

 INCLUSION

 To be enrolled, patients must:

 1. be veterans,

 2. have moderately severe CHF (NYHA class II, III or IV),

 3. be 18 or older,

 4. not have clinically important renal, hepatic or hematological disorders or clinically
 significant abnormal laboratory findings,

 5. not have a pre-existing thyroid disease,

 6. not have anemia (hematocrit less than 30%),

 7. not have chronic pulmonary disease that limits exercise tolerance or requires use of
 chronic bronchodilator therapy or steroids,

 8. be able to walk on the level for 6 minutes,

 9. not have hemodynamically significant pericardial disease,

 10. not have angina pectoris severe enough to require frequent administration of
 sublingual nitroglycerin,

 11. not have acute myocardial infarction within 6 months of screening,

 12. not have inoperable aortic stenosis,

 13. not have symptomatic ventricular arrhythmias or ventricular arrhythmia requiring
 pharmacological therapy,

 14. not have implanted cardioverter defibrillator,

 15. not be taking amiodarone,

 16. not have demonstrated non-compliance with prior medical regimes;

 17. not be on an investigational drug,

 18. not have a medical condition that, in the investigator's opinion, would make the
 patient ineligible,

 19. not have an allergy to iodine or shellfish,

 20. not be in sinus rhythm,

 21. not be of childbearing potential,

 22. have an ejection fraction greater than 40%.

 Exclusion Criteria: