Stem Cell Mobilization by G-CSF to Treat Severe Peripheral Artery Disease (STEMPAD)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT00797056
First received: November 20, 2008
Last updated: March 30, 2015
Last verified: March 2015
  Purpose

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.


Condition Intervention Phase
Peripheral Vascular Diseases
Drug: G-CSF
Drug: Placebo
Drug: Aspirin
Drug: Clopidogrel
Phase 0

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Pilot Study of Stem Cell Mobilization by G-CSF to Treat Severe Peripheral Artery Disease (STEMPAD Trial)

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Major limb amputation rate as defined by amputations of the limb that are transmetarsal and higher [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Toe pressure index [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]

    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 [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    • 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 [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    • 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 [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]

    -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.


Enrollment: 32
Study Start Date: April 2008
Study Completion Date: April 2012
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: G-CSF Drug: G-CSF
G-CSF 5 mcg/kg/day SQ daily for 10 days
Other Names:
  • Filgrastim
  • Neupogen
Drug: Aspirin
Aspirin 75 mg/day for 14 days
Other Name: acetylsalicylate
Drug: Clopidogrel
Clopidogrel 75mg/day daily for 14 days
Other Name: Plavix
Placebo Comparator: Placebo Drug: Placebo
Saline SQ daily for 10 days
Other Name: NaCl
Drug: Aspirin
Aspirin 75 mg/day for 14 days
Other Name: acetylsalicylate
Drug: Clopidogrel
Clopidogrel 75mg/day daily for 14 days
Other Name: Plavix

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00797056

Locations
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: Patrick Geraghty, M.D. Washington University School of Medicine
  More Information

Additional Information:
No publications provided

Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00797056     History of Changes
Other Study ID Numbers: 07-0043 / 201106083
Study First Received: November 20, 2008
Last Updated: March 30, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Washington University School of Medicine:
G-CSF
angiogenesis
endothelial progenitor cell
limb ischemia
revascularization

Additional relevant MeSH terms:
Peripheral Arterial Disease
Peripheral Vascular Diseases
Vascular Diseases
Arterial Occlusive Diseases
Arteriosclerosis
Atherosclerosis
Cardiovascular Diseases
Clopidogrel
Lenograstim
Adjuvants, Immunologic
Hematologic Agents
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Platelet Aggregation Inhibitors
Purinergic Agents
Purinergic Antagonists
Purinergic P2 Receptor Antagonists
Purinergic P2Y Receptor Antagonists
Therapeutic Uses

ClinicalTrials.gov processed this record on June 29, 2015