The DIAMOND Study: Distensibility Improvement And Remodeling in Diastolic Heart Failure

NCT00043836 | Completed Phase 2

• 1 other identifier: ALT-711-0214
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to test the hypothesis that treatment with oral ALT-711 twice daily for 16 weeks will improve aortic distensibility, exercise tolerance, and quality of life in elderly patients with isolated diastolic heart failure (DHF), and that the improvements in exercise tolerance will correlate with the improvements in aortic distensibility.

Conditions

Heart Failure, Congestive; Dyspnea; Pulmonary Edema

Keywords

ejection fraction; exercise tolerance; heart failure, congestive; quality of life

Interventions

ALT-711 DRUG

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men or women ≥ 60 years of age.
• Diagnosis of congestive heart failure with one or both of the following criteria: a Heart Failure Clinical Score ≥ 3 based on the NHANES-I criteria and/or a history of either acute pulmonary edema or the occurrence of 2 or more of the following with subsequent improvement with diuretic therapy and with no other identifiable cause: dyspnea on exertion, paroxysmal nocturnal dyspnea, orthopnea, systemic edema, exertional fatigue.
• Left ventricular ejection fraction ≥ 50% based on the baseline Doppler echocardiography test.
• Ability to provide written informed consent.
• Ability to comply with procedures specified in the study protocol.

You may not qualify if:

• Valvular heart disease as the primary etiology of congestive heart failure.
• Significant change in cardiovascular medication(s) \<3 weeks prior to the baseline visit.
• Uncontrolled hypertension.
• History of stroke, or any sequelae of a transient ischemic attack (TIA), reversible ischemic neurologic defect (RIND), or stroke, within the last 12 months prior to entry into the study.
• Cancer or other noncardiovascular conditions with life expectancy less than 2 years.
• Significant anemia defined as a hemoglobin \<11 gm/dL.
• Significant renal insufficiency defined as a serum creatinine \>2.5 mg/dL.
• Significant hepatic insufficiency defined as an SGPT (ALT) or SGOT (AST) \>2.5 times the upper limit of normal.
• Psychiatric disease (including uncontrolled major psychoses, depression, dementia, or personality disorder) or any additional condition(s) which, in the investigator's opinion, would prohibit the patient from completing the study, or not be in the best interest of the patient.
• Presence or history of drug or alcohol abuse.
• Prior exposure to ALT-711 or use of any other investigational drugs within 30 days prior to screening.
• Known seropositivity for HIV or hepatitis C, or presence of hepatitis B surface antigen.
• Severe COPD requiring recurrent oral steroids, oxygen at home or more than one inhaler.
• Baseline echocardiogram demonstrating the presence of left ventricular ejection fraction \<50%.
• Unstable or uncontrolled myocardial ischemia, with no wall abnormality.

Sponsors & Collaborators

• Synvista Therapeutics, Inc: lead

Study Sites (2)

Wake Forest University Baptist Medical Center, Department of Cardiology

Winston-Salem, North Carolina, 27157-1045, United States

Location

Medical University of South Carolina and Ralph H. Johnson VA Medical Center

Charleston, South Carolina, 29425 and 29401, United States

Location

Related Publications (16)

• Asif M, Egan J, Vasan S, Jyothirmayi GN, Masurekar MR, Lopez S, Williams C, Torres RL, Wagle D, Ulrich P, Cerami A, Brines M, Regan TJ. An advanced glycation endproduct cross-link breaker can reverse age-related increases in myocardial stiffness. Proc Natl Acad Sci U S A. 2000 Mar 14;97(6):2809-13. doi: 10.1073/pnas.040558497.

  PMID: 10706607 BACKGROUND

• Hundley WG, Kitzman DW, Morgan TM, Hamilton CA, Darty SN, Stewart KP, Herrington DM, Link KM, Little WC. Cardiac cycle-dependent changes in aortic area and distensibility are reduced in older patients with isolated diastolic heart failure and correlate with exercise intolerance. J Am Coll Cardiol. 2001 Sep;38(3):796-802. doi: 10.1016/s0735-1097(01)01447-4.

  PMID: 11527636 BACKGROUND

• Kass DA, Shapiro EP, Kawaguchi M, Capriotti AR, Scuteri A, deGroof RC, Lakatta EG. Improved arterial compliance by a novel advanced glycation end-product crosslink breaker. Circulation. 2001 Sep 25;104(13):1464-70. doi: 10.1161/hc3801.097806.

  PMID: 11571237 BACKGROUND

• Kitzman DW, Gardin JM, Gottdiener JS, Arnold A, Boineau R, Aurigemma G, Marino EK, Lyles M, Cushman M, Enright PL; Cardiovascular Health Study Research Group. Importance of heart failure with preserved systolic function in patients > or = 65 years of age. CHS Research Group. Cardiovascular Health Study. Am J Cardiol. 2001 Feb 15;87(4):413-9. doi: 10.1016/s0002-9149(00)01393-x.

  PMID: 11179524 BACKGROUND

• Kitzman DW. Heart Failure in the Elderly: Systolic and Diastolic Dysfunction. Am J Geriatr Cardiol. 1996 Jan;5(1):20-26. No abstract available.

  PMID: 11416361 BACKGROUND

• Little WC, Ohno M, Kitzman DW, Thomas JD, Cheng CP. Determination of left ventricular chamber stiffness from the time for deceleration of early left ventricular filling. Circulation. 1995 Oct 1;92(7):1933-9. doi: 10.1161/01.cir.92.7.1933.

  PMID: 7671378 BACKGROUND

• Marburger CT, Brubaker PH, Pollock WE, Morgan TM, Kitzman DW. Reproducibility of cardiopulmonary exercise testing in elderly patients with congestive heart failure. Am J Cardiol. 1998 Oct 1;82(7):905-9. doi: 10.1016/s0002-9149(98)00502-5.

  PMID: 9781977 BACKGROUND

• Vaitkevicius PV, Lane M, Spurgeon H, Ingram DK, Roth GS, Egan JJ, Vasan S, Wagle DR, Ulrich P, Brines M, Wuerth JP, Cerami A, Lakatta EG. A cross-link breaker has sustained effects on arterial and ventricular properties in older rhesus monkeys. Proc Natl Acad Sci U S A. 2001 Jan 30;98(3):1171-5. doi: 10.1073/pnas.98.3.1171.

  PMID: 11158613 BACKGROUND

• Warner JG Jr, Metzger DC, Kitzman DW, Wesley DJ, Little WC. Losartan improves exercise tolerance in patients with diastolic dysfunction and a hypertensive response to exercise. J Am Coll Cardiol. 1999 May;33(6):1567-72. doi: 10.1016/s0735-1097(99)00048-0.

  PMID: 10334425 BACKGROUND

• Wolffenbuttel BH, Boulanger CM, Crijns FR, Huijberts MS, Poitevin P, Swennen GN, Vasan S, Egan JJ, Ulrich P, Cerami A, Levy BI. Breakers of advanced glycation end products restore large artery properties in experimental diabetes. Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4630-4. doi: 10.1073/pnas.95.8.4630.

  PMID: 9539789 BACKGROUND

• Zile MR, Brutsaert DL. New concepts in diastolic dysfunction and diastolic heart failure: Part I: diagnosis, prognosis, and measurements of diastolic function. Circulation. 2002 Mar 19;105(11):1387-93. doi: 10.1161/hc1102.105289. No abstract available.

  PMID: 11901053 BACKGROUND

• Zile MR, Brutsaert DL. New concepts in diastolic dysfunction and diastolic heart failure: Part II: causal mechanisms and treatment. Circulation. 2002 Mar 26;105(12):1503-8. doi: 10.1161/hc1202.105290. No abstract available.

  PMID: 11914262 BACKGROUND

• Zile MR, Gaasch WH, Carroll JD, Feldman MD, Aurigemma GP, Schaer GL, Ghali JK, Liebson PR. Heart failure with a normal ejection fraction: is measurement of diastolic function necessary to make the diagnosis of diastolic heart failure? Circulation. 2001 Aug 14;104(7):779-82. doi: 10.1161/hc3201.094226.

  PMID: 11502702 BACKGROUND

• Kitzman DW. Diastolic heart failure in the elderly. Heart Fail Rev. 2002 Jan;7(1):17-27. doi: 10.1023/a:1013745705318.

  PMID: 11790920 BACKGROUND

• Kitzman DW. Heart failure with normal systolic function. Clin Geriatr Med. 2000 Aug;16(3):489-512. doi: 10.1016/s0749-0690(05)70025-2.

  PMID: 10918644 BACKGROUND

• Kitzman DW. Diastolic dysfunction in the elderly. Genesis and diagnostic and therapeutic implications. Cardiol Clin. 2000 Aug;18(3):597-617, x. doi: 10.1016/s0733-8651(05)70164-8.

  PMID: 10986592 BACKGROUND

MeSH Terms

Conditions

Heart Failure; Dyspnea; Pulmonary Edema

Interventions

alagebrium

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Lung Diseases

Study Officials

• Dalane W Kitzman, MD

  Associate Professor of Medicine and Cardiology, Wake Forest University Baptist Medical Center

  PRINCIPAL INVESTIGATOR

• Michael R Zile, MD

  Charles Ezra Daniel Professor of Medicine, Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: August 14, 2002
• First Posted: August 15, 2002
• Study Start: July 1, 2002
• Primary Completion: February 1, 2003
• Study Completion: October 1, 2005
• Last Updated: September 2, 2009

Record last verified: 2007-08

Locations

US (2)