search
Back to results

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

Primary Purpose

Peripheral Arterial Disease

Status
Terminated
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Dipyridamole 200mg and Aspirin 25mg bid:
Dipyridamole 200 mg bid
Aspirin 25 mg bid
Sponsored by
University of Pennsylvania
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Peripheral Arterial Disease focused on measuring Peripheral Arterial Disease, PAD, Claudication, Peripheral Vascular Disease

Eligibility Criteria

18 Years - 79 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Presbyterian Hospital, 51 N. 39th St.
  • Translational Research Ctr.,3400 Civic Center Blvd, Building 421, 10th floor, Room 421
  • University of Pennsylvania

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Active Comparator

Arm Label

Dipyridamole 200mg and Aspirin 25mg bid

Dipyridamole 200 mg bid

Aspirin 25 mg bid

Arm Description

All subjects in this arm will take their assigned medication for 180 days and complete study visits on Day 1(Baseline), 30, 90 and 180. All subjects will bring a 24 hour urine collection and arrive in a fasting state on all visit days for a blood draw after which they will receive breakfast. After assessing vitals, Adverse Event status and medication compliance, they will be escorted to the vascular labs for Doppler Ultrasound and Near Infrared Spectroscopy. (NIRS) of the legs.

All subjects in this arm will take their assigned medication for 180 days and complete study visits on Day 1(Baseline), 30, 90 and 180. All subjects will bring a 24 hour urine collection and arrive in a fasting state on all visit days for a blood draw after which they will receive breakfast. After assessing vitals, Adverse Event status and medication compliance, they will be escorted to the vascular labs for Doppler Ultrasound and Near Infrared Spectroscopy. (NIRS) of the legs.

All subjects in this arm will take their assigned medication for 180 days and complete study visits on Day 1(Baseline), 30, 90 and 180. All subjects will bring a 24 hour urine collection and arrive in a fasting state on all visit days for a blood draw after which they will receive breakfast. After assessing vitals, Adverse Event status and medication compliance, they will be escorted to the vascular labs for Doppler Ultrasound and Near Infrared Spectroscopy (NIRS) of the legs.

Outcomes

Primary Outcome Measures

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.
No analysis could be performed due to the insufficent number of participants enrolled. Data were not collected due to study termination related to the difficulty finding participants that matched the inclusion/exclusion criteria.

Secondary Outcome Measures

Assess the Functional Consequences of Dipyridamole Action, Alone and in Combination With Aspirin Compared With Aspirin Alone on Local Measurements of Flow and Oxygenation. Blood Flow Reporting to Added Table.
Done by doppler ultrasound. Data could not be analyzed due to insufficient number of participants enrolled. Data were not collected due to study termination related to the difficulty finding participants that matched the inclusion/exclusion criteria.
Assess the Functional Consequences of Dipyridamole Action, Alone and in Combination With Aspirin Compared With Aspirin Alone on Local Measurements of Flow and Oxygenation. Reporting Blood Oxygenation.
Reporting blood oxygenation. Data could not be analyzed due to insufficient number of participants enrolled. Difficulty finding participants who fit into the inclusion/exclusion criteria.

Full Information

First Posted
May 20, 2009
Last Updated
August 2, 2017
Sponsor
University of Pennsylvania
Collaborators
Boehringer Ingelheim
search

1. Study Identification

Unique Protocol Identification Number
NCT00906035
Brief Title
The Vascular Biology of Dipyridamole in Peripheral Arterial Disease (PAD)
Official Title
The Vascular Biology of Dipyridamole in Peripheral Arterial Disease (PAD)
Study Type
Interventional

2. Study Status

Record Verification Date
August 2017
Overall Recruitment Status
Terminated
Why Stopped
Could not enroll subjects who met the stringent inclusion/exclusion criteria.
Study Start Date
September 2002 (undefined)
Primary Completion Date
March 2010 (Actual)
Study Completion Date
April 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Pennsylvania
Collaborators
Boehringer Ingelheim

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief 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.
Detailed 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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Peripheral Arterial Disease
Keywords
Peripheral Arterial Disease, PAD, Claudication, Peripheral Vascular Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
25 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Dipyridamole 200mg and Aspirin 25mg bid
Arm Type
Active Comparator
Arm Description
All subjects in this arm will take their assigned medication for 180 days and complete study visits on Day 1(Baseline), 30, 90 and 180. All subjects will bring a 24 hour urine collection and arrive in a fasting state on all visit days for a blood draw after which they will receive breakfast. After assessing vitals, Adverse Event status and medication compliance, they will be escorted to the vascular labs for Doppler Ultrasound and Near Infrared Spectroscopy. (NIRS) of the legs.
Arm Title
Dipyridamole 200 mg bid
Arm Type
Active Comparator
Arm Description
All subjects in this arm will take their assigned medication for 180 days and complete study visits on Day 1(Baseline), 30, 90 and 180. All subjects will bring a 24 hour urine collection and arrive in a fasting state on all visit days for a blood draw after which they will receive breakfast. After assessing vitals, Adverse Event status and medication compliance, they will be escorted to the vascular labs for Doppler Ultrasound and Near Infrared Spectroscopy. (NIRS) of the legs.
Arm Title
Aspirin 25 mg bid
Arm Type
Active Comparator
Arm Description
All subjects in this arm will take their assigned medication for 180 days and complete study visits on Day 1(Baseline), 30, 90 and 180. All subjects will bring a 24 hour urine collection and arrive in a fasting state on all visit days for a blood draw after which they will receive breakfast. After assessing vitals, Adverse Event status and medication compliance, they will be escorted to the vascular labs for Doppler Ultrasound and Near Infrared Spectroscopy (NIRS) of the legs.
Intervention Type
Drug
Intervention Name(s)
Dipyridamole 200mg and Aspirin 25mg bid:
Other Intervention Name(s)
Persantine
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Dipyridamole 200 mg bid
Other Intervention Name(s)
Persantine
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Aspirin 25 mg bid
Intervention Description
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.
Primary Outcome Measure Information:
Title
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.
Description
No analysis could be performed due to the insufficent number of participants enrolled. Data were not collected due to study termination related to the difficulty finding participants that matched the inclusion/exclusion criteria.
Time Frame
Predose and dosing days 30, 90 and 180
Secondary Outcome Measure Information:
Title
Assess the Functional Consequences of Dipyridamole Action, Alone and in Combination With Aspirin Compared With Aspirin Alone on Local Measurements of Flow and Oxygenation. Blood Flow Reporting to Added Table.
Description
Done by doppler ultrasound. Data could not be analyzed due to insufficient number of participants enrolled. Data were not collected due to study termination related to the difficulty finding participants that matched the inclusion/exclusion criteria.
Time Frame
Predose and dosing days 30, 90 and 180.
Title
Assess the Functional Consequences of Dipyridamole Action, Alone and in Combination With Aspirin Compared With Aspirin Alone on Local Measurements of Flow and Oxygenation. Reporting Blood Oxygenation.
Description
Reporting blood oxygenation. Data could not be analyzed due to insufficient number of participants enrolled. Difficulty finding participants who fit into the inclusion/exclusion criteria.
Time Frame
Predose and dosing days 30, 90 and 180.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
79 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Garret A FitzGerald, MD
Organizational Affiliation
University of Pennsylvania
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Emile R Mohler, MD
Organizational Affiliation
University of Pennsylvania
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Tilo Grosser, MD
Organizational Affiliation
University of Pennsylvania
Official's Role
Principal Investigator
Facility Information:
Facility Name
Presbyterian Hospital, 51 N. 39th St.
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Translational Research Ctr.,3400 Civic Center Blvd, Building 421, 10th floor, Room 421
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs