Clinical Utility of Endothelial Dysfunction in PAD

NCT00491751 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: H-23184
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 1

Brief Summary

This study will seek to determine whether non-invasive measures of endothelial function have utility as surrogate markers of cardiovascular risk in patients with peripheral arterial disease undergoing vascular surgery. Measurements of endothelial function will be made before and after initiation of atorvastatin, ascorbic acid, or placebo therapy during the pre-operative period. We will then examine cardiovascular events following surgery. We hypothesize that patients who have no improvement in endothelial function will have increased cardiovascular risk compared to patients with improvement in endothelial function.

Conditions

Peripheral Arterial Disease

Keywords

endothelium; nitric oxide; statins; ascorbic acid

Outcome Measures

Primary Outcomes (1)

• Change in FMD

  Change in flow mediated dilation with treatment: FMD visit 2 - FMD visit 1 FMD is measured by using vascular ultrasound to determine the baseline diameter of the brachial artery. Endothelium-dependent vasodilation is induced by 5-minute arterial occlusion with a blood pressure cuff. When the cuff is released, the resultant increase in blood flow (reactive hyperemia) stimulates vasodilation of the brachial artery. This flow-mediated dilation (FMD) is expressed as the percent change from baseline. Healthy individuals typical dysplay a 10 to 12% dilation. Individuals with PAD had markedly impaired dilation of 6-7. The currernt study sought to determine whether a change in FMD would occur following intervention.

  1-4 weeks

Secondary Outcomes (1)

• Percentage Change in FMD in All Participants With and Without a CVD Event (Not by Treatment Group)

  2 months

Study Arms (3)

Atorvastatin

EXPERIMENTAL

Atorvastatin 40 or 80 mg/day

Drug: atorvastatin

Ascorbic Acid

EXPERIMENTAL

Ascorbic Acid 500 mg/day

Drug: ascorbic acid

Placebo

PLACEBO COMPARATOR

Placebo atorvastatin and Placebo ascorbic acid

Drug: Placebo

Interventions

atorvastatin DRUG

atorvastatin 40 or 80 mg/day

Also known as: Lipitor

Atorvastatin

ascorbic acid DRUG

ascorbic acid 500 mg/day

Also known as: Vitamin C

Ascorbic Acid

Placebo DRUG

matching placebo

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female subjects age 21-99 years old.
• Peripheral Arterial Disease. PAD is defined clinically and by angiography, magnetic resonance imaging, vascular ultrasound, or ankle brachial index less than 0.9.
• Able to provide informed consent and complete the study procedure.
• Patients undergoing non-emergent vascular surgery (peripheral arterial bypass, abdominal aortic aneurysm repair, carotid endarterectomy, or limb amputation) or other non-cardiac surgery.

You may not qualify if:

• Emergent or urgent surgery that must be performed sooner than one week after enrollment
• Unstable angina, myocardial infarction, stroke, coronary revascularization, or decompensated heart failure within 1 month of enrollment. Patients who require cardiac catheterization and surgical or percutaneous coronary revascularization prior to vascular surgery will be excluded.
• Clinically evident major illness of other organ systems, including cancer, end-stage renal disease, hepatic failure, or other conditions that make participation inappropriate.
• Women who are lactating, pregnant, or of childbearing potential and not using a reliable contraceptive method. Pregnancy will be excluded by a urine pregnancy test.
• Patients with liver function tests or serum creatine kinase \>3 times the upper limit of normal.
• Patients who have received an investigational drug within 30 days of enrollment.
• Patients or subjects with a history of a psychological illness or condition such as to interfere with the subject's ability to understand the requirements of the study.
• Known occlusive atherosclerosis of the subclavian artery or upper extremity, because such disease will interfere with induction of reactive hyperemia during the brachial artery ultrasound studies.
• Patients will be excluded if they are taking vitamin C in a dose greater than 2 times the Recommended Daily Allowance (\>120 mg/day) within 1 month of enrollment.

Sponsors & Collaborators

• Boston University: lead

Study Sites (1)

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

MeSH Terms

Conditions

Peripheral Arterial Disease

Interventions

Atorvastatin; Ascorbic Acid

Condition Hierarchy (Ancestors)

Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids; Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates

Limitations and Caveats

The study was terminated after enrollment of 108 of 450 subjects due to inability to enroll a sufficient number of subjects. Enrollment was difficult because nearly all potential subjects were already taking a statin.

Results Point of Contact

• Title: Naomi M. Hamburg, MD
• Organization: Boston University School of Medicine

nhamburg@bu.edu

617-638-7462

Study Officials

• Naomi Hamburg, MD

  Boston University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2007
• First Posted: June 26, 2007
• Study Start: May 1, 2004
• Primary Completion: June 1, 2012
• Study Completion: June 1, 2012
• Last Updated: July 27, 2018
• Results First Posted: July 27, 2018

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)