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

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Synvista Therapeutics, Inc
ClinicalTrials.gov Identifier:
NCT00277875
First received: January 13, 2006
Last updated: August 26, 2009
Last verified: January 2006
  Purpose

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).


Condition Intervention Phase
Cardiovascular Disease
Drug: ALT-711 (alagebrium chloride)
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Single Blind
Primary Purpose: Diagnostic
Official Title: The Effect of Vascular Distensibility on Endothelial-Dependent Vasoreactivity in Patients With Systolic Hypertension Before and After Receiving Oral Alagebrium for 8 Weeks.

Resource links provided by NLM:


Further study details as provided by Synvista Therapeutics, Inc:

Primary Outcome Measures:
  • Endothelial function
  • Local distensibility
  • Arterial stiffening
  • Augmentation index (AI)
  • Markers of endothelial function, vascular inflammation and collagen synthesis.

Estimated Enrollment: 25
Study Start Date: February 2004
Study Completion Date: January 2006
Primary Completion Date: December 2004 (Final data collection date for primary outcome measure)
Detailed Description:
  • Explore several independent variables as potential independent predictors of vascular stiffness and endothelial function. These parameters include patient age, body mass index, gender, renal disease, history of cardiovascular disease, serum cholesterol, and antihypertensive medication use.
  • Provide insight into nitric oxide-dependent endothelial function in the setting of increased arterial stiffness by determination of substances in the nitric oxide signaling pathway (specifically, levels of serum cGMP; serum nitrate and nitrite; and serum asymmetric dimethylarginine [ADMA], an endogenous inhibitor of nitric oxide synthase).
  • Provide insight into changes in AGE levels and collagen metabolism in response to alagebrium therapy [specifically, AGEs: pentosidine, carboxymethyllysine, carboxyethyllysine, furosine; Collagen markers: procollagen I carboxyterminal propeptide (PICP), procollagen type I N terminal propeptide (PINP), cross-linked carboxyterminal telopeptide of Type I collagen (ICTP), n-terminal propeptide of type III procollagen (PIIINP)].
  • Provide insight into changes in markers of inflammation in response to alagebrium therapy [specifically, free and total serum matrix metalloproteinase-1(MMP-1), free tissue inhibitor of metalloproteinase 1 (TIMP1), intercellular adhesion molecule-1 (ICAM), P-selectin, von Willebrand factor (vWf), interleukin-6 (IL-6), and high-sensitivity C reactive protein (hs CRP)].
  Eligibility

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female 50 years of age or greater.
  2. 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).
  3. Normal left ventricular function (ejection fraction >55%) at baseline (Visit 3).
  4. Able to perform bicycle exercise.
  5. Able to read, understand and sign the informed consent after the nature of the study has been explained.
  6. 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.

Exclusion Criteria:

  1. Aortic stenosis, prior known coronary artery disease (including myocardial infarction), cerebrovascular accident, or peripheral vascular disease.
  2. Uncontrolled hypertension (SBP > 200/ DBP > 95 mm Hg).
  3. Atrial fibrillation, diabetes mellitus treated with insulin, or chronic lung disease.
  4. 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.
  5. Treatment with nitrates, or a change in antihypertensive medications within the last 1 month.
  6. Treatment with any investigational drug within 1 month prior to study drug administration.
  7. Previous exposure to alagebrium.
  8. AST (SGOT) or ALT (SGPT) > 2x normal limit.
  9. Serum creatinine > 2.0 ng/mL.
  10. Cigar/cigarette smoking.
  11. 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.
  12. Positive drug screen.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00277875

Locations
United States, Maryland
Johns Hopkins University School of Medicine
Baltimore, Maryland, United States, 21287
Sponsors and Collaborators
Synvista Therapeutics, Inc
Investigators
Principal Investigator: Susan Zieman, MD, PhD Johns Hopkins University
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00277875     History of Changes
Other Study ID Numbers: ALT-711-0217
Study First Received: January 13, 2006
Last Updated: August 26, 2009
Health Authority: United States: Food and Drug Administration

Keywords provided by Synvista Therapeutics, Inc:
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

Additional relevant MeSH terms:
Cardiovascular Diseases

ClinicalTrials.gov processed this record on September 30, 2014