Granulocyte-Macrophage Stimulating Factor in the Treatment of Peripheral Arterial Disease

NCT01041417 | Completed Phase 2 Results DMC

• 2 other identifiers: IRB000303621RC2HL101515-01
• Study Type: interventional
• Target: 159
• Locations: 1 country
• Sites: 1

Brief Summary

Peripheral arterial disease is a common condition in older adults involving poor arterial circulation in the legs leading to leg pain and debility. The body's own circulating blood vessel stem cells may help to improve circulation. This study will test whether treatment with the drug granulocyte macrophage colony stimulating factor (GM-CSF) will improve symptoms and signs of peripheral arterial disease over placebo after four weeks of therapy. As well this study will examine whether improvements in blood vessel function can be observed. Finally, we will measure blood vessel function and stem cell levels in order to determine whether they can help to predict whether patients wither peripheral arterial disease will suffer further cardiovascular complications.

Conditions

Peripheral Arterial Disease

Keywords

claudication

Outcome Measures

Primary Outcomes (1)

• Change in Peak Walking Time During Treadmill Exercise Tolerance Test From Baseline to 3 Months

  Exercise Tolerance Test (ETT) was conducted using the Gardner protocol. Participants exercised on a treadmill, starting at 2.0 mph. The intensity of exercise (speed) was increased in grade of 2% every 2 minutes. Participants were asked to exercise until symptom limitation and the time measured in seconds from the ETT was used for data analysis.

  Baseline, 3 months

Secondary Outcomes (15)

• Change in Peak Walking Time During Treadmill Exercise Tolerance Test From Baseline to 6 Months

  Baseline, 6 months

• Change in Claudication Onset Time (COT) From Baseline to 3 Months

  Baseline, 3 months

• Change in Claudication Onset Time (COT) From Baseline to 6 Months

  Baseline, 6 months

• Change in Walking Distance Scores on Walking Impairment Questionnaire (WIQ) From Baseline to 3 Months

  Baseline, 3 months

• Change in Walking Distance Scores on Walking Impairment Questionnaire (WIQ) From Baseline to 6 Months

  Baseline, 6 months

Study Arms (2)

GM-CSF

EXPERIMENTAL

Subjects will receive GM-CSF 500μg (Sargramostim (Leukine), Sanofi Aventis) by a self-administered subcutaneous injection thrice weekly on Monday, Wednesday, and Friday for four weeks

Drug: Granulocyte-Macrophage Stimulating Factor (GM-CSF)

Placebo

PLACEBO COMPARATOR

Subjects will receive a saline injection (placebo) by a self-administered subcutaneous injection thrice weekly on Monday, Wednesday, and Friday for four weeks

Drug: Placebo

Interventions

Granulocyte-Macrophage Stimulating Factor (GM-CSF) DRUG

500 micrograms of GM-CSF

Also known as: GM-CSF, Leukine

GM-CSF

Placebo DRUG

Saline injection

Placebo

Eligibility Criteria

• Age: 21 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• males or post-menopausal females between 21 and 80 years of age. Female subjects must be (a) post-menopausal, (b) surgically sterile or (c) use adequate birth control and have a negative pregnancy test within 3 days prior to administration of study drug and should not be breastfeeding.
• Documented PAD (By Ankle-Brachial Indices or Angiographically)
• Clinically stable (at least 2 months) history of intermittent claudication with no change in symptom severity in the 2 months prior to screening.
• On stable statin therapy for previous 3 months.
• Peak Walking Time (PWT) between 1 and 12 minutes on a standardized Gardner treadmill protocol.
• A Doppler-derived ankle-brachial index (ABI) of \< 0.85 in the symptomatic limb after 10 minutes of rest at screening. For subjects with an ABI of \>1.3 (non-compressible arteries) a Toe-Brachial Index (TBI) of \< 0.70 must be obtained for subject qualification, or if ABI is \> 0.85 to 1.0 , and a reduction of 20% in ABI measured within 1 minute of treadmill testing.
• On appropriate and stable medical therapy for atherosclerosis for at least 2 months.
• Able to give informed consent.
• Diabetics with a dilated eye exam excluding proliferative retinopathy in the previous 12 months.

You may not qualify if:

• Recent or current active infections (treated with antibiotics).
• Recent (3 months) change in statin therapy
• Critical limb ischemia either chronic (category 3 and 4 of SVS classification) or acute ischemia manifested by rest pain, ulceration, or gangrene.
• Lower extremity vascular surgery, angioplasty or lumbar sympathectomy within 3 months of enrollment.
• Participation in a structured exercise treatment protocol within 3 months of enrollment.
• Prior myeloid cancer.
• Unstable angina, myocardial infarction, TIA, stroke or revascularization in the preceding 4 months.
• Severe heart failure (Class III or IV), heart muscle disease or atrial fibrillation.
• Limitation on exercise for symptoms other than intermittent claudication such as arthritis or dyspnea.
• Uncontrolled diabetes mellitus (defined as HbA1c \> 10.0).
• Chronic renal disease (creatinine of \>2.5 mg/dl) or hepatic disease (\> 3 X elevations in AST and ALT).
• Ophthalmologic conditions associated with a neo-vascular response.
• Alcohol or drug abuse, or any other disease process that, in the opinion of the PI, will interfere with the ability of the patient to participate in the study.

Sponsors & Collaborators

• Emory University: lead
• National Institutes of Health (NIH): collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Emory University

Atlanta, Georgia, 30322, United States

Location

Related Publications (1)

• Poole J, Mavromatis K, Binongo JN, Khan A, Li Q, Khayata M, Rocco E, Topel M, Zhang X, Brown C, Corriere MA, Murrow J, Sher S, Clement S, Ashraf K, Rashed A, Kabbany T, Neuman R, Morris A, Ali A, Hayek S, Oshinski J, Yoon YS, Waller EK, Quyyumi AA. Effect of progenitor cell mobilization with granulocyte-macrophage colony-stimulating factor in patients with peripheral artery disease: a randomized clinical trial. JAMA. 2013 Dec 25;310(24):2631-9. doi: 10.1001/jama.2013.282540.

  PMID: 24247554 DERIVED

MeSH Terms

Conditions

Peripheral Arterial Disease; Intermittent Claudication

Interventions

Granulocyte-Macrophage Colony-Stimulating Factor; sargramostim

Condition Hierarchy (Ancestors)

Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Limitations and Caveats

Study population were subjects with claudication who underwent angiography. Study design could not show therapeutic benefit of GM-CSF therapy with dose and duration changes. And study design encouraged all subjects to walk to claudication daily.

Results Point of Contact

• Title: Dr. Arshed Quyyumi
• Organization: Emory University School of Medicine

aquyyum@emory.edu

4047273655

Study Officials

• Arshed Quyyumi, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 29, 2009
• First Posted: December 31, 2009
• Study Start: September 1, 2009
• Primary Completion: March 1, 2014
• Last Updated: December 23, 2014
• Results First Posted: December 23, 2014

Record last verified: 2014-12

Locations

US (1)