The Vascular Biology of Dipyridamole in Peripheral Arterial Disease (PAD)

Peripheral Arterial Disease Clinical Trial

Official title:

The Vascular Biology of Dipyridamole in Peripheral Arterial Disease (PAD)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00906035
• Other study ID #: 706469
• Secondary ID: 0821
• Status: Terminated
• Phase: N/A
• First received: May 20, 2009
• Last updated: January 31, 2013
• Start date: September 2002
• Est. completion date: April 2010

Study information

• Verified date: November 2011
• Source: University of Pennsylvania
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

This research study will evaluate the effects of aspirin and dipyridamole alone and in combination on the blood flow in the vessels of the legs. We will examine how these medications are able to inhibit the clotting of platelets in the vessels of patients with PAD, and thereby affect the blood flow in the legs. Platelets are cells in the blood that have the ability to adhere to each other to form clots.

Description:

Dipyridamole has been reformulated to guarantee systemic bioavailability and steady state levels compatible with inhibition of platelet aggregation ex vivo (1). This newly formulated dipyridamole has been shown to roughly equal in efficacy to low dose aspirin in the secondary prevention of stroke and the drug combination seems roughly additive (2). The present study is designed to explore two potential mechanisms which have been linked to dipyridamole action on the vessel wall; modulation of vascular eicosanoid generation and prevention of oxidant stress (3). We shall address the hypothesis that dipyridamole affects these systems in patients with PAD. These individuals have disordered platelet-vascular interactions, as reflected by increased generation of thromboxane, an index of platelet activation and of prostacyclin, probably a homeostatic response to traumatic and chemical stimulation of the endothelium (4,5). Furthermore, we shall assess the functional consequences of dipyridamole action, alone and in combination with aspirin compared with aspirin alone on local measurements of flow and oxygenation, including exercise tolerance, Doppler Ultrasound and Near Infrared Spectroscopy (NIRS). Lipid peroxidation will be quantified based on mass spectrometric analysis of the major urinary isoprostane, 8,12-iso-iPF2a-VI (6,7).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 51
• Est. completion date: April 2010
• Est. primary completion date: March 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 79 Years

Eligibility

Inclusion Criteria:

• Age between 18 - 79

• Women of child bearing potential using a medically acceptable method of birth control (oral/transdermal/vaginal hormonal contraception, depo-provera injection, IUD, condom with spermicide, progestin implant, tubal ligation, oophorectomy, TAH) or abstinence.

• Capacity for giving written consent

• Diagnosis of PAD by:

• previous angiogram (>0.5 stenosis of a peripheral artery)

• ankle-brachial index (ABI) of systolic pressure <0.80

• previous peripheral revascularization

• Smokers who smoke < 10 cigarettes / day

Exclusion Criteria:

• Female subjects who are pregnant or nursing a child.

• Prior bleeding event related to drug therapy

• History of gastrointestinal ulceration

• History of known dipyridamole and/or aspirin allergy or intolerance

• History of coagulation, bleeding or blood disorders.

• Recent history of myocardial infarction or stroke in the previous 6 months

• Resting blood pressure of <110mmHg systolic or <60mmHg diastolic or of >165mmHg systolic or >95mmHg diastolic

• Patients with active infection as documented by abnormal laboratory tests at screen

• Concomitant serious illness, such as cancer, as per the principal investigator's discretion

• Current use of steroids for a chronic disease process

• Presence of ischemic leg ulcers

• History of contact allergies to the metal leads of the NIRS

• History of drug or alcohol abuse within the last 6 months.

• Subject who has received an experimental drug and/or used an experimental device within 30 days of screening.

• Subject who has donated = one pint of blood within 8 weeks prior to screen.

• Use of aspirin for 2 weeks prior to the study

• Use of any other NSAID or COX-inhibitor for one week prior to the start of the study

• Use of any antioxidant vitamin for 2 weeks prior to the start of the study

• Use of plavix, pletal or trental for one week prior to the start of the study

• Use of acetaminophen for one week prior to each study visit

• Use of alcohol, caffeine or high fat foods for 24 hours prior to each study visit

• Has smoked any cigarettes for 24 hours prior to each study visit

• Platelet aggregation blood test less than 60 percent at Visit 1

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Peripheral Arterial Disease
• Peripheral Vascular Diseases

Intervention

Drug:
• Dipyridamole 200mg and Aspirin 25mg bid:
All subjects will receive their randomly assigned study medication to be taken each morning and evening approximately 8am and 8 pm for the 180 day duration of the study.
• Dipyridamole 200 mg bid
All subjects will receive their randomly assigned study medication to be taken each morning and evening approximately 8am and 8 pm for the 180 day duration of the study.
• Aspirin 25 mg bid
All subjects will receive their randomly assigned study medication to be taken each morning and evening approximately 8am and 8 pm for the 180 day duration of the study.

Locations

Country	Name	City	State
United States	University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
University of Pennsylvania	Boehringer Ingelheim

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The present study is designed to explore two potential mechanisms which have been linked to dipyridamole action on the vessel wall; modulation of vascular eicosanoid generation and prevention of oxidant stress.		Predose and dosing days 30, 90 and 180	No
Secondary	Assess the functional consequences of dipyridamole action, alone and in combination with aspirin compared with aspirin alone on local measurements of flow and oxygenation.		Predose and dosing days 30, 90 and 180.	No