Stem Cell Mobilization by G-CSF to Treat Severe Peripheral Artery Disease (STEMPAD)
Primary Purpose
Peripheral Vascular Diseases
Status
Completed
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
G-CSF
Placebo
Aspirin
Clopidogrel
Sponsored by
About this trial
This is an interventional treatment trial for Peripheral Vascular Diseases focused on measuring G-CSF, angiogenesis, endothelial progenitor cell, limb ischemia, revascularization
Eligibility Criteria
Inclusion Criteria:
- Patients must have critical limb ischemia secondary to PAD, as defined by the presence of a non-healing ulcer, rest pain, or dry gangrene.
- Patients must have a toe pressure ≤ 30 mm Hg.
- Patients must be ≥18 years old.
- Patient must be able to self-administer a daily subcutaneous injection or have a caregiver who is able to administer a daily subcutaneous injection.
- Patients must be taking or have no absolute contraindication to taking aspirin and clopidogrel. If they are not currently taking aspirin, they must be willing to take aspirin (81 mg daily) and clopidogrel (75 mg daily) for 14 days starting on the first day of G-CSF treatment.
- After being informed of the treatment involved, patients must give written consent. The patient should not have any serious medical or psychiatric illness that would prevent either the giving of informed consent or the receipt of treatment. A built-in period of one week from discussion of the trial and initiation of the trial will be mandatory for enrollment.
Exclusion Criteria:
- Patients with transmetatarsal or higher amputations in the affected limb are excluded.
- Patients who are candidates for a revascularization procedure.
Sites / Locations
- Washington University School of Medicine
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
G-CSF
Placebo
Arm Description
Outcomes
Primary Outcome Measures
Major limb amputation rate as defined by amputations of the limb that are transmetarsal and higher
Secondary Outcome Measures
Toe pressure index
Toe brachial index (TBI) and is a calculation based on the systolic blood pressures of the arm and the systolic blood pressures of the toes. The examination is performed with a photoplethysmograph (PPG) infrared light sensor and a very small blood pressure cuff placed around the toe.
The arm and big toe systolic blood pressure measurements are recorded. Then the big toe systolic pressures are divided by the highest arm pressure to establish an TBI measurement for each leg. A TBI of .75 or greater is consider normal.
Ankle-brachial index
The Ankle Brachial Index (ABI or ABPI) is the ratio of the blood pressure in the lower legs to the blood pressure in the arms. Compared to the arm, lower blood pressure in the leg is an indication of blocked arteries (peripheral vascular disease or PVD). The ABI is calculated by dividing the systolic blood pressure at the ankle by the systolic blood pressures in the arm.
A normal resting ankle-brachial index is 1 or 1.1.
A resting ankle-brachial index of less than 1 is abnormal. If the ABI is:
Less than 0.95, significant narrowing of one or more blood vessels in the legs is indicated.
Less than 0.8, pain in the foot, leg, or buttock may occur during exercise (intermittent claudication).
Less than 0.4, symptoms may occur when at rest.
0.25 or below, severe limb-threatening peripheral artery disease is probably present.
Ulcer healing as measured by surface area and depth
Skin ulcerations should be selected on the basis of their size (lesions with the longest diameter) and their suitability for accurate repeat measurements. A maximum of 3 ulcers on each lower extremity will be followed.
An average of the longest diameter for all ulcerations will be calculated and reported as the baseline average longest diameter. The baseline average will be used as reference by which to characterize the ulcerations.
Improvement in rest pain as measured by the Vascular Quality of Life Questionnaire
-25 questions including questions in activity, symptom, pain, emotional, and social domains.
Each question has seven choices ranging from "All" to "None"
Each domain is scored 1-7=the total of domain item scores divided by the number of questions in the domain.
The total score is is also scored 1-7=the total of all the item scores divided by 25.
Full Information
NCT ID
NCT00797056
First Posted
November 20, 2008
Last Updated
March 30, 2015
Sponsor
Washington University School of Medicine
1. Study Identification
Unique Protocol Identification Number
NCT00797056
Brief Title
Stem Cell Mobilization by G-CSF to Treat Severe Peripheral Artery Disease
Acronym
STEMPAD
Official Title
Pilot Study of Stem Cell Mobilization by G-CSF to Treat Severe Peripheral Artery Disease (STEMPAD Trial)
Study Type
Interventional
2. Study Status
Record Verification Date
March 2015
Overall Recruitment Status
Completed
Study Start Date
April 2008 (undefined)
Primary Completion Date
April 2012 (Actual)
Study Completion Date
April 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Washington University School of Medicine
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study is designed to test the use of G-CSF in peripheral vascular disease. The investigators hypothesize that mobilization of angiogenic cells into the blood by granulocyte colony stimulating factor (G-CSF) may stimulate the formation of new blood vessels and result in a sustained improvement in blood flow in patients with severe peripheral arterial disease.
Detailed Description
One fourth of patients with peripheral artery disease (PAD) of the lower extremities have severe symptomatic disease and 1-2% have critical limb ischemia (CLI). In patients with CLI, the risk of limb amputation at 1 year is 50%. In addition, patients with CLI often have rest pain, non-healing ulcers and severe limitations of ambulation. Revascularization procedures, including bypass surgery, percutaneous transluminal angioplasty and angioplasty with stenting, are currently the only treatment options. However, many patients are not eligible for a revascularization procedure due to small vessel disease or coexisting medical problems. Moreover, restenosis rates are high.
There is currently no effective non-invasive treatment for critical limb ischemia. We hypothesize that mobilization of angiogenic cells into the blood by granulocyte colony stimulating factor (G-CSF) may stimulate angiogenesis in areas of ischemia and result in a sustained improvement in blood flow in patients with severe PAD.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Peripheral Vascular Diseases
Keywords
G-CSF, angiogenesis, endothelial progenitor cell, limb ischemia, revascularization
7. Study Design
Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
32 (Actual)
8. Arms, Groups, and Interventions
Arm Title
G-CSF
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
G-CSF
Other Intervention Name(s)
Filgrastim, Neupogen
Intervention Description
G-CSF 5 mcg/kg/day SQ daily for 10 days
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
NaCl
Intervention Description
Saline SQ daily for 10 days
Intervention Type
Drug
Intervention Name(s)
Aspirin
Other Intervention Name(s)
acetylsalicylate
Intervention Description
Aspirin 75 mg/day for 14 days
Intervention Type
Drug
Intervention Name(s)
Clopidogrel
Other Intervention Name(s)
Plavix
Intervention Description
Clopidogrel 75mg/day daily for 14 days
Primary Outcome Measure Information:
Title
Major limb amputation rate as defined by amputations of the limb that are transmetarsal and higher
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Toe pressure index
Description
Toe brachial index (TBI) and is a calculation based on the systolic blood pressures of the arm and the systolic blood pressures of the toes. The examination is performed with a photoplethysmograph (PPG) infrared light sensor and a very small blood pressure cuff placed around the toe.
The arm and big toe systolic blood pressure measurements are recorded. Then the big toe systolic pressures are divided by the highest arm pressure to establish an TBI measurement for each leg. A TBI of .75 or greater is consider normal.
Time Frame
Up to 1 year
Title
Ankle-brachial index
Description
The Ankle Brachial Index (ABI or ABPI) is the ratio of the blood pressure in the lower legs to the blood pressure in the arms. Compared to the arm, lower blood pressure in the leg is an indication of blocked arteries (peripheral vascular disease or PVD). The ABI is calculated by dividing the systolic blood pressure at the ankle by the systolic blood pressures in the arm.
A normal resting ankle-brachial index is 1 or 1.1.
A resting ankle-brachial index of less than 1 is abnormal. If the ABI is:
Less than 0.95, significant narrowing of one or more blood vessels in the legs is indicated.
Less than 0.8, pain in the foot, leg, or buttock may occur during exercise (intermittent claudication).
Less than 0.4, symptoms may occur when at rest.
0.25 or below, severe limb-threatening peripheral artery disease is probably present.
Time Frame
Up to 1 year
Title
Ulcer healing as measured by surface area and depth
Description
Skin ulcerations should be selected on the basis of their size (lesions with the longest diameter) and their suitability for accurate repeat measurements. A maximum of 3 ulcers on each lower extremity will be followed.
An average of the longest diameter for all ulcerations will be calculated and reported as the baseline average longest diameter. The baseline average will be used as reference by which to characterize the ulcerations.
Time Frame
Up to 1 year
Title
Improvement in rest pain as measured by the Vascular Quality of Life Questionnaire
Description
-25 questions including questions in activity, symptom, pain, emotional, and social domains.
Each question has seven choices ranging from "All" to "None"
Each domain is scored 1-7=the total of domain item scores divided by the number of questions in the domain.
The total score is is also scored 1-7=the total of all the item scores divided by 25.
Time Frame
Up to 1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients must have critical limb ischemia secondary to PAD, as defined by the presence of a non-healing ulcer, rest pain, or dry gangrene.
Patients must have a toe pressure ≤ 30 mm Hg.
Patients must be ≥18 years old.
Patient must be able to self-administer a daily subcutaneous injection or have a caregiver who is able to administer a daily subcutaneous injection.
Patients must be taking or have no absolute contraindication to taking aspirin and clopidogrel. If they are not currently taking aspirin, they must be willing to take aspirin (81 mg daily) and clopidogrel (75 mg daily) for 14 days starting on the first day of G-CSF treatment.
After being informed of the treatment involved, patients must give written consent. The patient should not have any serious medical or psychiatric illness that would prevent either the giving of informed consent or the receipt of treatment. A built-in period of one week from discussion of the trial and initiation of the trial will be mandatory for enrollment.
Exclusion Criteria:
Patients with transmetatarsal or higher amputations in the affected limb are excluded.
Patients who are candidates for a revascularization procedure.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Patrick Geraghty, M.D.
Organizational Affiliation
Washington University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Washington University School of Medicine
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
12. IPD Sharing Statement
Links:
URL
http://www.siteman.wustl.edu
Description
Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
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Stem Cell Mobilization by G-CSF to Treat Severe Peripheral Artery Disease
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