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

Cardiovascular Disease Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00277875
• Other study ID #: ALT-711-0217
• Status: Completed
• Phase: Phase 2
• First received: January 13, 2006
• Last updated: August 26, 2009
• Start date: February 2004
• Est. completion date: January 2006

Study information

• Verified date: January 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

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).

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)].

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: January 2006
• Est. primary completion date: December 2004
• 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. 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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Single Group Assignment, Masking: Single Blind, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Cardiovascular Disease
• Cardiovascular Diseases

Intervention

Drug:
• ALT-711 (alagebrium chloride)

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Synvista Therapeutics, Inc	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

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. — 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

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Endothelial function
Primary	Local distensibility
Primary	Arterial stiffening
Primary	Augmentation index (AI)
Primary	Markers of endothelial function, vascular inflammation and collagen synthesis.