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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00277875
Recruitment Status : Completed
First Posted : January 18, 2006
Last Update Posted : August 27, 2009
National Institutes of Health (NIH)
Information provided by:
Synvista Therapeutics, Inc

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).

Condition or disease Intervention/treatment Phase
Cardiovascular Disease Drug: ALT-711 (alagebrium chloride) Phase 2

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)].

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Study Type : Interventional  (Clinical Trial)
Enrollment : 25 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Single
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.
Study Start Date : February 2004
Actual Primary Completion Date : December 2004
Actual Study Completion Date : January 2006

Resource links provided by the National Library of Medicine

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

Information from the National Library of Medicine

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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00277875

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United States, Maryland
Johns Hopkins University School of Medicine
Baltimore, Maryland, United States, 21287
Sponsors and Collaborators
Synvista Therapeutics, Inc
National Institutes of Health (NIH)
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Principal Investigator: Susan Zieman, MD, PhD Johns Hopkins University

Layout table for additonal information Identifier: NCT00277875     History of Changes
Other Study ID Numbers: ALT-711-0217
First Posted: January 18, 2006    Key Record Dates
Last Update Posted: August 27, 2009
Last Verified: January 2006

Keywords provided by Synvista Therapeutics, Inc:
Flow-Mediated Vasodilation (FMD)
Pulse Perfusion-Mediated Vasodilation (PPMV)
Endothelial Function
Heart Failure
Local Distensibility
Arterial Stiffening
Augmentation Index (AI)
Isolated Systolic Hypertension
Advanced Glycation Endproducts
Vascular Stiffness

Additional relevant MeSH terms:
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Cardiovascular Diseases