STRETCH Study: Effect of Distensibility on Endothelial-Dependent Vasoreactivity in Patients With ISH

NCT00277875 | Completed Phase 2

• 1 other identifier: ALT-711-0217
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

Determine whether increasing arterial distensibility by decreasing advanced glycation end-product (AGE) cross-link components of vascular stiffness improves (a) endothelial-mediated vasoreactivity at rest, as assessed by flow-mediated vasodilation (FMD), and (b) endothelial-mediated vasoreactivity after exercise, as assessed by pulse perfusion-mediated vasodilation (PPMV).

Conditions

Cardiovascular Disease

Keywords

Cardiovascular; Flow-Mediated Vasodilation (FMD); Pulse Perfusion-Mediated Vasodilation (PPMV); Endothelial Function; Heart Failure; Local Distensibility; Arterial Stiffening; Augmentation Index (AI); Aging; Isolated Systolic Hypertension; Advanced Glycation Endproducts; Vascular Stiffness

Outcome Measures

Primary Outcomes (5)

• Endothelial function

• Local distensibility

• Arterial stiffening

• Augmentation index (AI)

• Markers of endothelial function, vascular inflammation and collagen synthesis.

Interventions

ALT-711 (alagebrium chloride) DRUG

Eligibility Criteria

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

You may qualify if:

• Male or female 50 years of age or greater.
• Diagnosed with systolic hypertension (systolic blood pressure \>140 mm Hg and (less than or equal to) 200 mm Hg, and a diastolic blood pressure (less than or equal to) 95 mm Hg) and elevated pulse pressure (systolic blood pressure \[SBP\] minus diastolic blood pressure \[DBP\] greater than 60 mm Hg).
• Normal left ventricular function (ejection fraction \>55%) at baseline (Visit 3).
• Able to perform bicycle exercise.
• Able to read, understand and sign the informed consent after the nature of the study has been explained.
• If sexually active, the patient agrees to use reliable contraception while participating in this study. If a woman, is surgically sterilized or post-menopausal, or has a negative serum pregnancy test.

You may not qualify if:

• Aortic stenosis, prior known coronary artery disease (including myocardial infarction), cerebrovascular accident, or peripheral vascular disease.
• Uncontrolled hypertension (SBP \> 200/ DBP \> 95 mm Hg).
• Atrial fibrillation, diabetes mellitus treated with insulin, or chronic lung disease.
• Any additional condition(s) which, in the opinion of the investigator, would prohibit the patient from completing the study, or not be in the best interest of the patient.
• Treatment with nitrates, or a change in antihypertensive medications within the last 1 month.
• Treatment with any investigational drug within 1 month prior to study drug administration.
• Previous exposure to alagebrium.
• AST (SGOT) or ALT (SGPT) \> 2x normal limit.
• Serum creatinine \> 2.0 ng/mL.
• Cigar/cigarette smoking.
• Necessity to use smokeless tobacco or nicotine-containing products, or to consume caffeine, alcohol, or antioxidants starting at midnight prior to study clinic visits. NOTE: Water is allowed ad libitim.
• Positive drug screen.

Sponsors & Collaborators

• Synvista Therapeutics, Inc: lead
• National Institutes of Health (NIH): collaborator

Study Sites (1)

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21287, United States

Location

Related Publications (4)

• 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

• Liu ZR, Ting CT, Zhu SX, Yin FC. Aortic compliance in human hypertension. Hypertension. 1989 Aug;14(2):129-36. doi: 10.1161/01.hyp.14.2.129.

  PMID: 2759675 BACKGROUND

• Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, Creager MA, Deanfield J, Drexler H, Gerhard-Herman M, Herrington D, Vallance P, Vita J, Vogel R; International Brachial Artery Reactivity Task Force. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol. 2002 Jan 16;39(2):257-65. doi: 10.1016/s0735-1097(01)01746-6.

  PMID: 11788217 BACKGROUND

• Deng YB, Wang XF, Le GR, Zhang QP, Li CL, Zhang YG. Evaluation of endothelial function in hypertensive elderly patients by high-resolution ultrasonography. Clin Cardiol. 1999 Nov;22(11):705-10. doi: 10.1002/clc.4960221105.

  PMID: 10554684 BACKGROUND

MeSH Terms

Conditions

Cardiovascular Diseases; Heart Failure; Isolated Systolic Hypertension

Interventions

alagebrium

Condition Hierarchy (Ancestors)

Heart Diseases; Essential Hypertension; Hypertension; Vascular Diseases

Study Officials

• Susan Zieman, MD, PhD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: January 13, 2006
• First Posted: January 18, 2006
• Study Start: February 1, 2004
• Primary Completion: December 1, 2004
• Study Completion: January 1, 2006
• Last Updated: August 27, 2009

Record last verified: 2006-01

Locations

US (1)