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

Synvista Therapeutics

Status and phase: Completed; Phase 2

Conditions: Dyspnea; Heart Failure, Congestive; Pulmonary Edema

Treatments: Drug: ALT-711

Study type: Interventional

Funder types: Industry

Identifiers

NCT00043836

ALT-711-0214

Details and patient eligibility

About

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.

Sex: All

Ages: 60+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

1. Men or women ≥ 60 years of age.
2. 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.
3. Left ventricular ejection fraction ≥ 50% based on the baseline Doppler echocardiography test.
4. Ability to provide written informed consent.
5. Ability to comply with procedures specified in the study protocol.

Exclusion Criteria

1. Valvular heart disease as the primary etiology of congestive heart failure.
2. Significant change in cardiovascular medication(s) <3 weeks prior to the baseline visit.
3. Uncontrolled hypertension.
4. 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.
5. Cancer or other noncardiovascular conditions with life expectancy less than 2 years.
6. Significant anemia defined as a hemoglobin <11 gm/dL.
7. Significant renal insufficiency defined as a serum creatinine >2.5 mg/dL.
8. Significant hepatic insufficiency defined as an SGPT (ALT) or SGOT (AST) >2.5 times the upper limit of normal.
9. 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.
10. Presence or history of drug or alcohol abuse.
11. Prior exposure to ALT-711 or use of any other investigational drugs within 30 days prior to screening.
12. Known seropositivity for HIV or hepatitis C, or presence of hepatitis B surface antigen.
13. Severe COPD requiring recurrent oral steroids, oxygen at home or more than one inhaler.
14. Baseline echocardiogram demonstrating the presence of left ventricular ejection fraction <50%.
15. Unstable or uncontrolled myocardial ischemia, with no wall abnormality.
16. Screening Familiarization Exercise Test demonstrating the presence of any of the following findings: evidence of significant ischemia (consisting of ECG finding of > 1 mm flat ST depression confirmed with echocardiogram wall motion, or wall motion abnormality or decrease in global contractility on echocardiogram, or inability to continue exercising due to significant chest or leg pain or any reason other than exhaustion/fatigue/dyspnea, exercise SBP >240 mm Hg, DBP >110 mmHg, unstable hemodynamics or rhythm, or unwilling or unable to complete test adequately.
17. Any contraindications to magnetic resonance imaging including but not limited to indwelling metal-containing prosthesis (orthopedic, valvular, other), pacemaker or defibrillator, history of welding occupation (ocular metal debris), or uncontrollable claustrophobia.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)