Granulocyte-macrophage Colony Stimulating Factor In Patients With Intermittent Claudication - G-PAD

Description:

The goal of the trial was to evaluate treatment with granulocyte-macrophage colony stimulating factor (GM-CSF) compared with placebo among patients with intermittent claudication (IC).

Hypothesis:

GM-CSF would increase the exercise capacity of patients with intermittent claudication compared with placebo.

Study Design

Study Design:

Patients Enrolled: 45
Mean Follow Up: Three months
Mean Patient Age: Mean age 64 years
Female: 13

Patient Populations:

Intermittent claudication with no revascularization options.

Drug/Procedures Used:

Patients were randomized in a 2:1 double-blind manner to either GM-CSF (3, 6 or 10 mcg/kg; n=29) or placebo (n=16) three times per week for two weeks. Patients underwent exercise treadmill test, ankle brachial index (ABI) and lab tests at baseline and 3 months.

Principal Findings:

Endothelial progenitor cell (EPC) counts increased 31% from baseline to peak follow-up in the GM-CSF groups (p=0.026) but did not change significantly in the placebo group, as did circulating CD34+ cell counts (+46% for GM-CSF, p=0.036 and p=NS for placebo). There was no change in ankle brachial index from baseline to follow-up in the GM-CSF groups (0.58 at both timepoints) or in the placebo group (0.61 at baseline and 0.57 at 12 weeks). Pain-free walking time (PFWT) increased at follow-up in the GM-CSF therapy group, from 113 sec to 151 sec (p=0.008), but did not differ in the placebo group (130 sec to 145 sec). Likewise, total walking time (TWT) increased at follow-up in the GM-CSF therapy group, from 287 sec to 342 sec (p=0.016), but did not differ in the placebo group (322 sec to 331 sec). There was no apparent dose response relationship. Adverse events were more frequent in the GM-CSF group, including injection site rash (n=13 vs n=1), fever (n=5 vs n=0), and myalgias/arthralgias (n=5 vs n=0).

Interpretation:

Among patients with intermittent claudication, treatment with granulocyte-macrophage colony stimulating factor was associated with improvements in ETT walking time at follow-up, but was not associated with changes in ABI.

While the present study demonstrated some improvements in walking time in the GM-CSF group at follow-up compared with baseline and no difference in the placebo group, a head-to-head comparison of the changes in the GM-CSF group and the changes in the placebo group was not presented. No dose-response relationship was observed with the three different doses. Adverse events were more frequent in the GM-CSF group, although the presenter noted that serious adverse events were rare.

References:

Presented by Dr. Veerappan Subramaniyam at the March 2006 ACC Annual Scientific Session, Atlanta, GA.

Clinical Topics: Diabetes and Cardiometabolic Disease, Prevention, Vascular Medicine, Atherosclerotic Disease (CAD/PAD), Exercise

Keywords: Neutropenia, Intermittent Claudication, Arthralgia, Macrophage Colony-Stimulating Factor, Ankle Brachial Index, Stem Cells, Cell Count, Granulocyte-Macrophage Colony-Stimulating Factor, Peripheral Vascular Diseases, Walking, Exanthema, Exercise Test, Myalgia


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