DITPA (3,5-diiodothyropropionic acid), a thyroid hormone analog to treat heart failure: Phase II trial veterans affairs cooperative study

Steven Goldman, Madeline McCarren, Eugene Morkin, Paul W. Ladenson, Robert Edson, Stuart Warren, Janet Ohm, Hoang Thai, Lori Churby, Jamie Barnhill, Terrence O'Brien, Inder Anand, Alberta Warner, Brack Hattler, Mark Dunlap, John Erikson, Mei Chiung Shih, Phil Lavori

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

BACKGROUND: In animal studies and a pilot trial in patients with congestive heart failure, the thyroid hormone analog 3,5 diiodothyropropionic acid (DITPA) had beneficial hemodynamic effects. METHODS AND RESULTS: This was a phase II multicenter, randomized, placebo-controlled, double-blind trial of New York Heart Association class II to IV congestive heart failure patients randomized (2:1) to DITPA or placebo and treated for 6 months. The study enrolled 86 patients (n≤57 to DITPA, n≤29 to placebo). The primary objective was to assess the effect of DITPA on a composite congestive heart failure end point that classifies patients as improved, worsened, or unchanged based on symptom changes and morbidity/mortality. DITPA was poorly tolerated, which obscured the interpretation of congestive heart failurespecific effects. Fatigue and gastrointestinal complaints, in particular, were more frequent in the DITPA group. DITPA increased cardiac index (by 18%) and decreased systemic vascular resistance (by 11%), serum cholesterol (-20%), low-density lipoprotein cholesterol (-30%), and body weight (-11 lb). Thyroid-stimulating hormone was suppressed in patients given DITPA, which reflects its thyromimetic effect; however, no symptoms or signs of potential hypothyroidism or thyrotoxicosis were seen. CONCLUSIONS: DITPA improved some hemodynamic and metabolic parameters, but there was no evidence for symptomatic benefit in congestive heart failure.

Original languageEnglish (US)
Pages (from-to)3093-3100
Number of pages8
JournalCirculation
Volume119
Issue number24
DOIs
StatePublished - Jun 23 2009
Externally publishedYes

Fingerprint

Veterans
Thyroid Hormones
Heart Failure
Placebos
Hemodynamics
3,5-diiodothyropropionic acid
Thyrotoxicosis
Thyrotropin
Hypothyroidism
Vascular Resistance
LDL Cholesterol
Signs and Symptoms
Fatigue
Cholesterol
Body Weight
Morbidity
Mortality
Serum

Keywords

  • Cardiac output
  • Heart failure
  • Hemodynamics
  • Pharmacology
  • Thyroid

ASJC Scopus subject areas

  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Cite this

DITPA (3,5-diiodothyropropionic acid), a thyroid hormone analog to treat heart failure : Phase II trial veterans affairs cooperative study. / Goldman, Steven; McCarren, Madeline; Morkin, Eugene; Ladenson, Paul W.; Edson, Robert; Warren, Stuart; Ohm, Janet; Thai, Hoang; Churby, Lori; Barnhill, Jamie; O'Brien, Terrence; Anand, Inder; Warner, Alberta; Hattler, Brack; Dunlap, Mark; Erikson, John; Shih, Mei Chiung; Lavori, Phil.

In: Circulation, Vol. 119, No. 24, 23.06.2009, p. 3093-3100.

Research output: Contribution to journalArticle

Goldman, S, McCarren, M, Morkin, E, Ladenson, PW, Edson, R, Warren, S, Ohm, J, Thai, H, Churby, L, Barnhill, J, O'Brien, T, Anand, I, Warner, A, Hattler, B, Dunlap, M, Erikson, J, Shih, MC & Lavori, P 2009, 'DITPA (3,5-diiodothyropropionic acid), a thyroid hormone analog to treat heart failure: Phase II trial veterans affairs cooperative study', Circulation, vol. 119, no. 24, pp. 3093-3100. https://doi.org/10.1161/CIRCULATIONAHA.108.834424
Goldman, Steven ; McCarren, Madeline ; Morkin, Eugene ; Ladenson, Paul W. ; Edson, Robert ; Warren, Stuart ; Ohm, Janet ; Thai, Hoang ; Churby, Lori ; Barnhill, Jamie ; O'Brien, Terrence ; Anand, Inder ; Warner, Alberta ; Hattler, Brack ; Dunlap, Mark ; Erikson, John ; Shih, Mei Chiung ; Lavori, Phil. / DITPA (3,5-diiodothyropropionic acid), a thyroid hormone analog to treat heart failure : Phase II trial veterans affairs cooperative study. In: Circulation. 2009 ; Vol. 119, No. 24. pp. 3093-3100.
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abstract = "BACKGROUND: In animal studies and a pilot trial in patients with congestive heart failure, the thyroid hormone analog 3,5 diiodothyropropionic acid (DITPA) had beneficial hemodynamic effects. METHODS AND RESULTS: This was a phase II multicenter, randomized, placebo-controlled, double-blind trial of New York Heart Association class II to IV congestive heart failure patients randomized (2:1) to DITPA or placebo and treated for 6 months. The study enrolled 86 patients (n≤57 to DITPA, n≤29 to placebo). The primary objective was to assess the effect of DITPA on a composite congestive heart failure end point that classifies patients as improved, worsened, or unchanged based on symptom changes and morbidity/mortality. DITPA was poorly tolerated, which obscured the interpretation of congestive heart failurespecific effects. Fatigue and gastrointestinal complaints, in particular, were more frequent in the DITPA group. DITPA increased cardiac index (by 18{\%}) and decreased systemic vascular resistance (by 11{\%}), serum cholesterol (-20{\%}), low-density lipoprotein cholesterol (-30{\%}), and body weight (-11 lb). Thyroid-stimulating hormone was suppressed in patients given DITPA, which reflects its thyromimetic effect; however, no symptoms or signs of potential hypothyroidism or thyrotoxicosis were seen. CONCLUSIONS: DITPA improved some hemodynamic and metabolic parameters, but there was no evidence for symptomatic benefit in congestive heart failure.",
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AU - Ladenson, Paul W.

AU - Edson, Robert

AU - Warren, Stuart

AU - Ohm, Janet

AU - Thai, Hoang

AU - Churby, Lori

AU - Barnhill, Jamie

AU - O'Brien, Terrence

AU - Anand, Inder

AU - Warner, Alberta

AU - Hattler, Brack

AU - Dunlap, Mark

AU - Erikson, John

AU - Shih, Mei Chiung

AU - Lavori, Phil

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N2 - BACKGROUND: In animal studies and a pilot trial in patients with congestive heart failure, the thyroid hormone analog 3,5 diiodothyropropionic acid (DITPA) had beneficial hemodynamic effects. METHODS AND RESULTS: This was a phase II multicenter, randomized, placebo-controlled, double-blind trial of New York Heart Association class II to IV congestive heart failure patients randomized (2:1) to DITPA or placebo and treated for 6 months. The study enrolled 86 patients (n≤57 to DITPA, n≤29 to placebo). The primary objective was to assess the effect of DITPA on a composite congestive heart failure end point that classifies patients as improved, worsened, or unchanged based on symptom changes and morbidity/mortality. DITPA was poorly tolerated, which obscured the interpretation of congestive heart failurespecific effects. Fatigue and gastrointestinal complaints, in particular, were more frequent in the DITPA group. DITPA increased cardiac index (by 18%) and decreased systemic vascular resistance (by 11%), serum cholesterol (-20%), low-density lipoprotein cholesterol (-30%), and body weight (-11 lb). Thyroid-stimulating hormone was suppressed in patients given DITPA, which reflects its thyromimetic effect; however, no symptoms or signs of potential hypothyroidism or thyrotoxicosis were seen. CONCLUSIONS: DITPA improved some hemodynamic and metabolic parameters, but there was no evidence for symptomatic benefit in congestive heart failure.

AB - BACKGROUND: In animal studies and a pilot trial in patients with congestive heart failure, the thyroid hormone analog 3,5 diiodothyropropionic acid (DITPA) had beneficial hemodynamic effects. METHODS AND RESULTS: This was a phase II multicenter, randomized, placebo-controlled, double-blind trial of New York Heart Association class II to IV congestive heart failure patients randomized (2:1) to DITPA or placebo and treated for 6 months. The study enrolled 86 patients (n≤57 to DITPA, n≤29 to placebo). The primary objective was to assess the effect of DITPA on a composite congestive heart failure end point that classifies patients as improved, worsened, or unchanged based on symptom changes and morbidity/mortality. DITPA was poorly tolerated, which obscured the interpretation of congestive heart failurespecific effects. Fatigue and gastrointestinal complaints, in particular, were more frequent in the DITPA group. DITPA increased cardiac index (by 18%) and decreased systemic vascular resistance (by 11%), serum cholesterol (-20%), low-density lipoprotein cholesterol (-30%), and body weight (-11 lb). Thyroid-stimulating hormone was suppressed in patients given DITPA, which reflects its thyromimetic effect; however, no symptoms or signs of potential hypothyroidism or thyrotoxicosis were seen. CONCLUSIONS: DITPA improved some hemodynamic and metabolic parameters, but there was no evidence for symptomatic benefit in congestive heart failure.

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