The SAPPHIRE Study (Systolic And Pulse Pressure Hemodynamic Improvement By Restoring Elasticity)

NCT00045981 | Completed Phase 2

• 1 other identifier: ALT-711-0107
• Study Type: interventional
• Target: 450
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of ALT-711 in the treatment of isolated systolic hypertension in a formal dose-ranging study in patients without left ventricular hypertrophy. Eligible patients will be randomized to double-blind treatment once daily for 6 months with oral ALT-711 (35, 70, 140, or 210 mg) or placebo.

Conditions

Hypertension

Keywords

cardiovascular; aged; antihypertensive agents/therapeutic use; hypertension/*drug therapy; blood pressure

Interventions

ALT-711 DRUG

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men or women at least 50 years of age.
• Screening diagnosis of isolated systolic hypertension, defined as systolic blood pressure \>150 mm Hg and diastolic blood pressure \<90 mm Hg (office blood pressure measurements) and systolic blood pressure \>140 mm Hg (measured by 24-hour ambulatory blood pressure monitoring-mean daytime values).
• Baseline systolic blood pressure \>150 mm Hg and diastolic blood pressure \<90 mm Hg (office blood pressure measurements).
• Patients without left ventricular hypertrophy (LVH) as determined by limited echocardiography for LVH (i.e., wall thickness \< 1.2 cm).
• Patient can complete an informed consent.

You may not qualify if:

• Patient \<50 years of age.
• Patients on antihypertensive therapy with changes in dose in the last 1 month prior to the entry into the study.
• Hb A1c \> 9%.
• Serum creatinine \> 1.7mg/dL.
• History of ketoacidosis or uncontrolled diabetes within the last 2 years.
• History of congestive heart failure.
• History of stroke, or any sequelae of a transient ischemic attack, reversible ischemic neurologic defect, or stroke, within the last 12 months.
• History of acute myocardial infarction within 6 months prior to entry into the study.
• Any significant ECG abnormalities, including second degree AV-block or complete AV-block. Any known significant arrhythmia including atrial flutter, ventricular tachycardia, WPW-syndrome. Any hemodynamically significant valvular heart disease.
• Any significant systemic illnesses or medical condition that could lead to difficulty complying with the protocol.
• Screening or Baseline liver function tests SGOT and/or SGPT \> 2.0 times the upper limits of central laboratory normal range.
• Use of systemic and/or inhaled corticosteroids (excluding topical corticosteroids).
• 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.
• Use of any investigational drugs within 30 days prior to screening.
• Previous exposure to ALT-711.

Sponsors & Collaborators

• Synvista Therapeutics, Inc: lead

Related Publications (10)

• 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

• 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

• 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

• 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

• Chobanian AV. Control of hypertension--an important national priority. N Engl J Med. 2001 Aug 16;345(7):534-5. doi: 10.1056/NEJM200108163450709. No abstract available.

  PMID: 11519509 BACKGROUND

• Hyman DJ, Pavlik VN. Characteristics of patients with uncontrolled hypertension in the United States. N Engl J Med. 2001 Aug 16;345(7):479-86. doi: 10.1056/NEJMoa010273.

  PMID: 11519501 BACKGROUND

• Wilkinson IB, Webb Christison DJ, Cockcroft JR. Isolated systolic hypertension: a radical rethink. It's a risk factor that needs treatment, especially in the over 50s. BMJ. 2000 Jun 24;320(7251):1685. doi: 10.1136/bmj.320.7251.1685. No abstract available.

  PMID: 10864525 BACKGROUND

• Brownlee M, Vlassara H, Kooney A, Ulrich P, Cerami A. Aminoguanidine prevents diabetes-induced arterial wall protein cross-linking. Science. 1986 Jun 27;232(4758):1629-32. doi: 10.1126/science.3487117.

  PMID: 3487117 BACKGROUND

• McVeigh GE, Bratteli CW, Morgan DJ, Alinder CM, Glasser SP, Finkelstein SM, Cohn JN. Age-related abnormalities in arterial compliance identified by pressure pulse contour analysis: aging and arterial compliance. Hypertension. 1999 Jun;33(6):1392-8. doi: 10.1161/01.hyp.33.6.1392.

  PMID: 10373222 BACKGROUND

• Neaton JD, Wentworth D. Serum cholesterol, blood pressure, cigarette smoking, and death from coronary heart disease. Overall findings and differences by age for 316,099 white men. Multiple Risk Factor Intervention Trial Research Group. Arch Intern Med. 1992 Jan;152(1):56-64.

  PMID: 1728930 BACKGROUND

MeSH Terms

Conditions

Hypertension

Interventions

alagebrium

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Study Officials

• Milan Kovacevic, MD, PhD

  Synvista Therapeutics, Inc

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: September 17, 2002
• First Posted: September 19, 2002
• Study Start: October 1, 2001
• Primary Completion: May 1, 2003
• Study Completion: August 1, 2006
• Last Updated: March 26, 2010

Record last verified: 2007-08