Granulocyte-Macrophage Stimulating Factor (GM-CSF) in Peripheral Arterial Disease

NCT03304821 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: IRB000871981R61HL138657
• Study Type: interventional
• Target: 176
• Locations: 1 country
• Sites: 1

Brief Summary

Peripheral artery disease (PAD) is a disease in which plaque builds up in the arteries that carry blood to the head, organs, and limbs. PAD usually occurs in the arteries in the legs, but can affect any arteries. Over time, plaque can harden and narrow the arteries which limits the flow of oxygen-rich blood to organs and other parts of the body. Blocked blood flow to the arteries can cause pain and numbness. The pain is usually worse with exercise and gets better with rest. PAD can raise the risk of getting an infection which could lead to tissue death and amputation. This study is investigating whether granulocyte-macrophage colony stimulating factor (GM-CSF) improves symptoms and blood flow in people with PAD. GM-CSF is a drug that is used to stimulate the bone marrow to release stem cells. Participants in the study will be randomly selected to receive GM-CSF or a placebo. After a four-week screening phase, participants will receive injections of GM-CSF or a placebo three times a week for three-weeks. Three months later, participants will again receive injections of GM-CSF or placebo three times a week for three-weeks. At six months, the study team will follow up to see if the group that received GM-CSF had more improvement than the group that received placebo.

Conditions

Peripheral Artery Disease (PAD)

Keywords

Atherosclerotic peripheral artery disease; Granulocyte-macrophage colony stimulating factor (GM-CSF); Atherosclerosis; Cardiology; Vascular disease

Outcome Measures

Primary Outcomes (1)

• Change in 6-minute walk distance

  Participants will be walk up and down a 100-foot hallway for 6 minutes to cover the maximum distance possible. The distance, measured in feet, completed after 6 minutes will be recorded.

  Baseline, Month 3, Month 6, Month 9

Secondary Outcomes (8)

• Change in Peak Walking Time (PWT)

  Baseline, Month 3, Month 6, Month 9

• Change in Walking Impairment Questionnaire (WIQ): Walking Distance Score

  Baseline, Month 3, Month 6, Month 9, Follow-up Years 1, 2, and 3

• Change in Walking Impairment Questionnaire (WIQ): Walking Speed Score

  Baseline, Month 3, Month 6, Month 9, Follow-up Years 1, 2, and 3

• Change in Walking Impairment Questionnaire (WIQ): Stair Climbing Score

  Baseline, Month 3, Month 6, Month 9, Follow-up Years 1, 2, and 3

• Change in 36-item Short-Form Health Survey (SF-36) Score

  Baseline, Month 3, Month 6, Month 9, Follow-up Years 1, 2, and 3

Study Arms (2)

GM-CSF

EXPERIMENTAL

Participants receiving 500µg of granulocyte-macrophage colony stimulating factor (GM-CSF), administered subcutaneously. Prior to randomization to a study arm, eligible participants will be trained to perform subcutaneous injections and instructed to walk at least three times a day until they develop claudication or symptomatic limitation for 4 weeks.

Drug: GM-CSF

Placebo

PLACEBO COMPARATOR

Participants receiving 500µg of a placebo, administered subcutaneously. Prior to randomization to a study arm, eligible participants will be trained to perform subcutaneous injections and instructed to walk at least three times a day until they develop claudication or symptomatic limitation for 4 weeks.

Drug: Placebo

Interventions

GM-CSF DRUG

Participants will self-administer 500 μg/day of GM-CSF, subcutaneously, three times per week (Monday, Wednesday, Friday) for three weeks. After three months the participants will receive a second administration of 500 μg/day of subcutaneous GM-CSF, three times per week for another 3 weeks and then will be followed for another 3 months.

Also known as: Sargramostim, Leukine

GM-CSF

Placebo DRUG

Participants will self-administer 500 μg/day of a placebo, subcutaneously, three times per week (Monday, Wednesday, Friday) for three weeks. After three months the participants will receive a second administration of 500 μg/day of a placebo administered subcutaneously, three times per week for another 3 weeks and then will be followed for another 3 months.

Placebo

Eligibility Criteria

• Age: 21 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 symptomatic PAD
• Clinically stable (at least 2 months prior to enrollment) history of intermittent claudication or walking impairment (Rutherford Class II) with no change in symptom severity in the 2 months prior to screening.
• On statin therapy for previous 3 months prior to enrollment, unless statin intolerant.
• Peak Walking Time (PWT) between 1 and 12 minutes on a standardized Gardner treadmill protocol or modified Gardner protocol or less than 12 minutes on a modified Bruce protocol in case PWT on Gardner protocol is more than 12 minutes.
• A Doppler-derived ankle-brachial index (ABI) of \< 0.90 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 \> 0.9 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 prior to enrollment.
• Able to give informed consent.
• Diabetics with a dilated eye exam excluding proliferative retinopathy in the previous 12 months prior to enrollment.

You may not qualify if:

• Recent or current active infections (treated with antibiotics)
• Recent (6 months prior to randomization) or current active cancer undergoing treatment
• Recent (3 months prior to randomization) change in statin or cilostazol therapy
• Critical limb ischemia either chronic (Rutherford Class \>II) or acute ischemia manifested by rest pain, ulceration, or gangrene
• Recent (3 months prior to randomization) lower extremity vascular surgery, angioplasty or lumbar sympathectomy
• Planned participation in a structured exercise treatment protocol in the future or within period of study
• Prior myeloid malignancy
• Recent (3 months prior to randomization) Unstable angina, myocardial infarction, transient ischemic attack (TIA), stroke or revascularization
• Severe heart failure (Class III or IV) or heart muscle disease
• Limitation on exercise for symptoms other than intermittent claudication such as arthritis or dyspnea
• Below- or above-knee amputation; wheelchair confinement
• Use of a walking aid other than a cane
• Walking impairment for reasons other than PAD e.g. Parkinson's disease
• Uncontrolled diabetes mellitus (defined as HbA1c \> 10.0)
• Chronic renal disease (creatinine of \>2.5 mg/dl) or hepatic disease (\> 3 X elevations in aspartate aminotransferase (AST) and alanine aminotransferase (ALT))

Sponsors & Collaborators

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

Study Sites (1)

Emory University Hospital

Atlanta, Georgia, 30322, United States

RECRUITING

Related Publications (1)

• Mehta A, Mavromatis K, Ko YA, Rogers SC, Dhindsa DS, Goodwin C, Patel R, Martini MA, Prasad M, Mokhtari A, Hesaroieh IG, Frohwein SC, Kutner MH, Harzand A, Wells BJ, Duwayri Y, Alabi O, Rajani RR, Brewster LP, Waller EK, Quyyumi AA. Rationale and design of the granulocyte-macrophage colony stimulating factor in peripheral arterial disease (GPAD-3) study. Contemp Clin Trials. 2020 Apr;91:105975. doi: 10.1016/j.cct.2020.105975. Epub 2020 Mar 4.

  PMID: 32145440 DERIVED

MeSH Terms

Conditions

Peripheral Arterial Disease; Atherosclerosis; Vascular Diseases

Interventions

Granulocyte-Macrophage Colony-Stimulating Factor; sargramostim

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases

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

Study Officials

• Arshed Quyyumi, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kiran Ejaz

CONTACT

404-712-0169; Kiran.ejaz@emory.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Participants and the primary investigator will be blinded to group assignment. Blinding will be maintained by Investigational Pharmacy and blood counts will be reviewed by one of the study co-investigators who will make dose-modifications, when necessary.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Participants will be randomized, in a 2:1 manner, to receive: * Group A: Subcutaneous GM-CSF 500µg on Monday, Wednesday, Friday (n=117) * Group B: Placebo on Monday, Wednesday, Friday (n=59) Participants will be stratified on diabetes status ensuring that a proportionate number of diabetics (2:1) are randomized to each group.

Study Record Dates

• First Submitted: October 4, 2017
• First Posted: October 9, 2017
• Study Start: December 19, 2017
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: November 27, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)