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

Cardiovascular Disease Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00302250
• Other study ID #: ALT-711-0217 (Amended)
• Status: Completed
• Phase: Phase 2
• First received: March 13, 2006
• Last updated: March 21, 2006
• Start date: February 2006
• Est. completion date: December 2006

Study information

• Verified date: March 2006
• Source: Synvista Therapeutics, Inc
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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).

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: December 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 50 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cardiovascular Disease
• Cardiovascular Diseases
• Hypertension

Intervention

Drug:
• ALT-711 (alagebrium chloride)

Locations

Country	Name	City	State
United States	Johns Hopkins University School of Medicine	Baltimore	Maryland

Sponsors (3)

Lead Sponsor	Collaborator
Synvista Therapeutics, Inc	National Heart and Lung Institute, National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

References & Publications (4)

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. Erratum in: J Am Coll Cardiol 2002 Mar 20;39(6):1082. — View Citation

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. — View Citation

Little WC, Zile MR, Kitzman DW, Hundley WG, O'Brien TX, Degroof RC. The effect of alagebrium chloride (ALT-711), a novel glucose cross-link breaker, in the treatment of elderly patients with diastolic heart failure. J Card Fail. 2005 Apr;11(3):191-5. — View Citation

Liu ZR, Ting CT, Zhu SX, Yin FC. Aortic compliance in human hypertension. Hypertension. 1989 Aug;14(2):129-36. — View Citation