Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

The STRETCH Study: Distensibility on Endothelial-Dependent Vasoreactivity in Subjects With Systolic Hypertension

This study has been completed.
Sponsor:
Collaborators:
National Heart and Lung Institute
Information provided by:
Synvista Therapeutics, Inc
ClinicalTrials.gov Identifier:
NCT00302250
First received: March 13, 2006
Last updated: March 21, 2006
Last verified: March 2006
  Purpose

The primary objective of the double-blind segment is to compare effects of alagebrium vs placebo on change from baseline in endothelial function, as assessed by flow-mediated vasodilation (FMD).


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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Study of The Effect of Vascular Distensibility on Endothelial-Dependent Vasoreactivity in Subjects With Systolic Hypertension Before and After Receiving Oral Alagebrium or Placebo for 8 Weeks (STRETCH)

Resource links provided by NLM:


Further study details as provided by Synvista Therapeutics, Inc:

Estimated Enrollment: 70
Study Start Date: February 2006
Estimated Study Completion Date: December 2006
Detailed Description:

The secondary objectives of the double-blind segment are to:

  • Compare the effects of alagebrium vs placebo on the change from baseline in endothelial-mediated vasoreactivity immediately after exercise, as assessed by pulse perfusion-mediated vasodilation (PPMV).
  • Confirm results observed in the single-blind segment.
  • Explore several variables as potential independent predictors of vascular stiffness and endothelial function. These parameters include 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 the relationship between AGE levels (AGE markers: pentosidine, furosine), collagen metabolism (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]), and endothelial function; and insight into the changes in these markers in response to treatment with an AGE cross-link breaker (alagebrium).
  • Provide insight into the relationship between markers of inflammation [specifically, free and total serum matrix metalloproteinase-1(MMP-1), free tissue inhibitor of metalloproteinase 1 (TIMP1), intercellular adhesion molecule-1 (ICAM), vascular cellular adhesion molecule (VCAM), P-selectin, von Willebrand factor (vWf), interleukin-6 (IL-6), endothelin 1, VEGF, NFkβ, TGF-β, IGF-1 and high-sensitivity C reactive protein (hs CRP)] and endothelial function; and insight into the changes in these markers in response to treatment with an AGE cross-link breaker (alagebrium).
  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. Brachial artery must be able to be visualized for FMD and PPMV determinations.
  5. Able to perform bicycle exercise.
  6. Able to read, understand and sign the informed consent after the nature of the study has been explained.
  7. If sexually active, the subject 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 subject from completing the study, or not be in the best interest of the subject.
  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 mg/dL.
  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: NCT00302250

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

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00302250     History of Changes
Other Study ID Numbers: ALT-711-0217 (Amended)
Study First Received: March 13, 2006
Last Updated: March 21, 2006
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

Additional relevant MeSH terms:
Cardiovascular Diseases
Hypertension
Vascular Diseases

ClinicalTrials.gov processed this record on November 25, 2014