Trial Outcomes & Findings for Granulocyte-Macrophage Stimulating Factor in the Treatment of Peripheral Arterial Disease (NCT NCT01041417)

NCT ID: NCT01041417

Last Updated: 2014-12-23

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 159 participants
• Primary outcome timeframe: Baseline, 3 months
• Results posted on: 2014-12-23

Participant Flow

Between January 2010 and July 2012, 322 individuals with peripheral artery disease were assessed for eligibility. 159 subjects were enrolled into the study from Emory Healthcare, Veterans Affairs hospitals in Atlanta, and Medical College of Georgia.

Participant milestones

Measure	GM-CSF Granulocyte-Macrophage Colony Stimulating Factor injection - three times for four weeks 500 microgram dose of GM-CSF	Placebo Saline injection - three times for four weeks
Overall Study STARTED	80	79
Overall Study COMPLETED	73	76
Overall Study NOT COMPLETED	7	3

Reasons for withdrawal

Measure	GM-CSF Granulocyte-Macrophage Colony Stimulating Factor injection - three times for four weeks 500 microgram dose of GM-CSF	Placebo Saline injection - three times for four weeks
Overall Study Adverse Event	5	2
Overall Study Lost to Follow-up	1	1
Overall Study Death	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	GM-CSF n=80 Participants Granulocyte-Macrophage Colony Stimulating Factor injection - three times for four weeks 500 microgram dose of GM-CSF	Placebo n=79 Participants Saline injection - three times for four weeks	Total n=159 Participants Total of all reporting groups
Age, Continuous	64.3 years STANDARD_DEVIATION 7.9 • n=5 Participants	63.6 years STANDARD_DEVIATION 7.9 • n=7 Participants	63.9 years STANDARD_DEVIATION 7.9 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	10 Participants n=7 Participants	20 Participants n=5 Participants
Sex: Female, Male Male	70 Participants n=5 Participants	69 Participants n=7 Participants	139 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	45 Participants n=5 Participants	34 Participants n=7 Participants	79 Participants n=5 Participants
Race (NIH/OMB) White	33 Participants n=5 Participants	45 Participants n=7 Participants	78 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment United States	80 participants n=5 Participants	79 participants n=7 Participants	159 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, 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.

Outcome measures

Measure	GM-CSF n=73 Participants Granulocyte-Macrophage Colony Stimulating Factor injection - three times for four weeks 500 microgram dose of GM-CSF	Placebo n=76 Participants Saline injection - three times for four weeks
Change in Peak Walking Time During Treadmill Exercise Tolerance Test From Baseline to 3 Months	109 seconds 95% Confidence Interval 248 • Interval 67.0 to 151.0	56 seconds 95% Confidence Interval 182 • Interval 14.0 to 98.0

SECONDARY outcome

Timeframe: Baseline, 6 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.

Outcome measures

Measure	GM-CSF n=73 Participants Granulocyte-Macrophage Colony Stimulating Factor injection - three times for four weeks 500 microgram dose of GM-CSF	Placebo n=76 Participants Saline injection - three times for four weeks
Change in Peak Walking Time During Treadmill Exercise Tolerance Test From Baseline to 6 Months	112 seconds Interval 71.0 to 153.0	77 seconds Interval 36.0 to 117.0

SECONDARY outcome

Timeframe: Baseline, 3 months

Claudication is pain, tired or weak feeling that occurs in the legs, usually during activity such as walking. The COT was measured as the time to onset of the participant's typical claudication as the maximum distance the patient could walk on the treadmill.

Outcome measures

Measure	GM-CSF n=73 Participants Granulocyte-Macrophage Colony Stimulating Factor injection - three times for four weeks 500 microgram dose of GM-CSF	Placebo n=76 Participants Saline injection - three times for four weeks
Change in Claudication Onset Time (COT) From Baseline to 3 Months	81 seconds Interval 52.0 to 111.0	61 seconds Interval 32.0 to 91.0

SECONDARY outcome

Timeframe: Baseline, 6 months

Claudication is pain, tired or weak feeling that occurs in the legs, usually during activity such as walking. The COT was measured as the time to onset of the participant's typical claudication as the maximum distance the patient could walk on the treadmill.

Outcome measures

Measure	GM-CSF n=73 Participants Granulocyte-Macrophage Colony Stimulating Factor injection - three times for four weeks 500 microgram dose of GM-CSF	Placebo n=76 Participants Saline injection - three times for four weeks
Change in Claudication Onset Time (COT) From Baseline to 6 Months	93 seconds Interval 64.0 to 122.0	61 seconds Interval 33.0 to 89.0

SECONDARY outcome

Timeframe: Baseline, 3 months

The WIQ quantifies walking difficulty on a 100-point scale, in which 0 indicates extreme difficulty and 100 indicates no difficulty with walking distance.

Outcome measures

Measure	GM-CSF n=73 Participants Granulocyte-Macrophage Colony Stimulating Factor injection - three times for four weeks 500 microgram dose of GM-CSF	Placebo n=76 Participants Saline injection - three times for four weeks
Change in Walking Distance Scores on Walking Impairment Questionnaire (WIQ) From Baseline to 3 Months	12.5 units on a scale 95% Confidence Interval 27.6 • Interval 6.4 to 18.7	4.8 units on a scale 95% Confidence Interval 24.8 • Interval -0.2 to 9.8

SECONDARY outcome

Timeframe: Baseline, 6 months

The WIQ quantifies walking difficulty on a 100-point scale, in which 0 indicates extreme difficulty and 100 indicates no difficulty with walking distance.

Outcome measures

Measure	GM-CSF n=73 Participants Granulocyte-Macrophage Colony Stimulating Factor injection - three times for four weeks 500 microgram dose of GM-CSF	Placebo n=76 Participants Saline injection - three times for four weeks
Change in Walking Distance Scores on Walking Impairment Questionnaire (WIQ) From Baseline to 6 Months	8.0 units on a scale Interval 2.1 to 14.0	3.7 units on a scale Interval -0.9 to 8.3

SECONDARY outcome

Timeframe: Baseline, 3 months

The WIQ quantifies walking difficulty on a 100-point scale, in which 0 indicates extreme difficulty and 100 indicates no difficulty with walking speed.

Outcome measures

Measure	GM-CSF n=73 Participants Granulocyte-Macrophage Colony Stimulating Factor injection - three times for four weeks 500 microgram dose of GM-CSF	Placebo n=76 Participants Saline injection - three times for four weeks
Change in Walking Speed Score on Walking Impairment Questionnaire (WIQ) From Baseline to 3 Months	9.1 units on a scale Interval 4.2 to 14.0	7.5 units on a scale Interval 2.1 to 12.8

SECONDARY outcome

Timeframe: Baseline, 6 months

The WIQ quantifies walking difficulty on a 100-point scale, in which 0 indicates extreme difficulty and 100 indicates no difficulty with walking speed.

Outcome measures

Measure	GM-CSF n=73 Participants Granulocyte-Macrophage Colony Stimulating Factor injection - three times for four weeks 500 microgram dose of GM-CSF	Placebo n=76 Participants Saline injection - three times for four weeks
Change in Walking Speed Score on Walking Impairment Questionnaire (WIQ) From Baseline to 6 Months	9.9 units on a scale Interval 4.6 to 15.3	8.5 units on a scale Interval 3.8 to 13.2

SECONDARY outcome

Timeframe: Baseline, 3 months

The WIQ quantifies walking difficulty on a 100-point scale, in which 0 indicates extreme difficulty and 100 indicates no difficulty with stair climbing elements.

Outcome measures

Measure	GM-CSF n=73 Participants Granulocyte-Macrophage Colony Stimulating Factor injection - three times for four weeks 500 microgram dose of GM-CSF	Placebo n=76 Participants Saline injection - three times for four weeks
Change in Stair Climbing Score on Walking Impairment Questionnaire (WIQ) From Baseline to 3 Months	8.5 units on a scale Interval 3.0 to 13.9	4.2 units on a scale Interval -2.2 to 10.6

SECONDARY outcome

Timeframe: Baseline, 6 months

The WIQ quantifies walking difficulty on a 100-point scale, in which 0 indicates extreme difficulty and 100 indicates no difficulty with stair climbing elements.

Outcome measures

Measure	GM-CSF n=73 Participants Granulocyte-Macrophage Colony Stimulating Factor injection - three times for four weeks 500 microgram dose of GM-CSF	Placebo n=76 Participants Saline injection - three times for four weeks
Change in Stair Climbing Score on Walking Impairment Questionnaire (WIQ) From Baseline to 6 Months	10.4 units on a scale Interval 4.9 to 15.9	6.6 units on a scale Interval 1.2 to 11.9

SECONDARY outcome

Timeframe: Baseline, 3 months

The SF-36 is a standard quality of life instrument. The PCS represents the the physical burden on quality of life and is a summary of questions related to physical impact of a disease or condition (physical function, role physical, bodily pain, and general health). PCS is a summary measure derived from 8 scale score and the score ranges from 0-100; higher scores indicate better performance.

Outcome measures

Measure	GM-CSF n=73 Participants Granulocyte-Macrophage Colony Stimulating Factor injection - three times for four weeks 500 microgram dose of GM-CSF	Placebo n=76 Participants Saline injection - three times for four weeks
Change in Score on Physical Composite Score (PCS) Subscale of the Short Form 36 Health Survey (SF-36) From Baseline to 3 Months	4.1 units on a scale Interval 2.4 to 5.8	2.1 units on a scale Interval 0.5 to 3.7

SECONDARY outcome

Timeframe: Baseline, 6 months

The SF-36 is a standard quality of life instrument. The PCS represents the the physical burden on quality of life and is a summary of questions related to physical impact of a disease or condition (physical function, role physical, bodily pain, and general health). PCS is a summary measure derived from 8 scale score and the score ranges from 0-100; higher scores indicate better performance.

Outcome measures

Measure	GM-CSF n=73 Participants Granulocyte-Macrophage Colony Stimulating Factor injection - three times for four weeks 500 microgram dose of GM-CSF	Placebo n=76 Participants Saline injection - three times for four weeks
Change in Score on Physical Composite Score (PCS) Subscale of the Short Form 36 Health Survey (SF-36) From Baseline to 6 Months	5.2 units on a scale Interval 3.3 to 7.0	3.1 units on a scale Interval 1.5 to 4.7

SECONDARY outcome

Timeframe: Baseline, 3 months

The SF-36 is a standard quality of life instrument. The MCS represents the the mental burden on quality of life and is a summary of questions related to mental impact of a disease or condition (mental function, role emotional, vitality, and mental health). MCS is a summary measure derived from 8 scale score and the score ranges from 0-100; higher scores indicate better performance.

Outcome measures

Measure	GM-CSF n=73 Participants Granulocyte-Macrophage Colony Stimulating Factor injection - three times for four weeks 500 microgram dose of GM-CSF	Placebo n=76 Participants Saline injection - three times for four weeks
Change in Score on Mental Composite Score (MCS) Subscale of the Short Form 36 Health Survey (SF-36) From Baseline to 3 Months	0.7 units on a scale Interval -1.5 to 2.9	2.4 units on a scale Interval -0.2 to 5.0

SECONDARY outcome

Timeframe: Baseline, 6 months

The SF-36 is a standard quality of life instrument. The MCS represents the the mental burden on quality of life and is a summary of questions related to mental impact of a disease or condition (mental function, role emotional, vitality, and mental health). MCS is a summary measure derived from 8 scale score and the score ranges from 0-100; higher scores indicate better performance.

Outcome measures

Measure	GM-CSF n=73 Participants Granulocyte-Macrophage Colony Stimulating Factor injection - three times for four weeks 500 microgram dose of GM-CSF	Placebo n=76 Participants Saline injection - three times for four weeks
Change in Score on Mental Composite Score (MCS) Subscale of the Short Form 36 Health Survey (SF-36) From Baseline to 6 Months	-0.2 units on a scale Interval -2.4 to 2.0	1.1 units on a scale Interval -1.0 to 3.2

SECONDARY outcome

Timeframe: Baseline, 3 months

The SF-36 is a standard quality of life instrument. The physical functioning represents limitations in physical activities because of health problems. Physical functioning is a summary measure derived from 8 scale scores and the score ranges from 0-100; higher scores indicate better performance.

Outcome measures

Measure	GM-CSF n=73 Participants Granulocyte-Macrophage Colony Stimulating Factor injection - three times for four weeks 500 microgram dose of GM-CSF	Placebo n=76 Participants Saline injection - three times for four weeks
Change in Score on Physical Functioning Subscale of the Short Form 36 Health Survey (SF-36) From Baseline to 3 Months	11.4 units on a scale Interval 6.7 to 16.1	4.8 units on a scale Interval -0.1 to 9.6

SECONDARY outcome

Timeframe: Baseline, 6 months

The SF-36 is a standard quality of life instrument. The physical functioning represents limitations in physical activities because of health problems. Physical functioning is a summary measure derived from 8 scale scores and the score ranges from 0-100; higher scores indicate better performance.

Outcome measures

Measure	GM-CSF n=73 Participants Granulocyte-Macrophage Colony Stimulating Factor injection - three times for four weeks 500 microgram dose of GM-CSF	Placebo n=76 Participants Saline injection - three times for four weeks
Change in Score on Physical Functioning Subscale of the Short Form 36 Health Survey (SF-36) From Baseline to 6 Months	14.3 units on a scale Interval 9.7 to 18.9	8.1 units on a scale Interval 3.7 to 12.4

Adverse Events

GM-CSF

Serious events: 9 serious events

Other events: 79 other events

Deaths: 0 deaths

Placebo

Serious events: 9 serious events

Other events: 69 other events

Deaths: 0 deaths

Serious adverse events

Measure	GM-CSF n=80 participants at risk Granulocyte-Macrophage Colony Stimulating Factor injection - Monday, Wednesday and Friday for 4 weeks of therapy. 500 microgram dose of GM-CSF	Placebo n=79 participants at risk Saline injection - Monday, Wednesday and Friday for 4 weeks.
Social circumstances Death	1.4% 1/73 • Number of events 1 • Adverse events were collected at weeks 1, 2, 3, 4, 8 and 3 month follow-up and 6 month follow-up	0.00% 0/76 • Adverse events were collected at weeks 1, 2, 3, 4, 8 and 3 month follow-up and 6 month follow-up
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate Cancer	1.2% 1/80 • Number of events 1 • Adverse events were collected at weeks 1, 2, 3, 4, 8 and 3 month follow-up and 6 month follow-up	1.3% 1/79 • Number of events 1 • Adverse events were collected at weeks 1, 2, 3, 4, 8 and 3 month follow-up and 6 month follow-up
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Esophageal Cancer	1.2% 1/80 • Number of events 1 • Adverse events were collected at weeks 1, 2, 3, 4, 8 and 3 month follow-up and 6 month follow-up	0.00% 0/79 • Adverse events were collected at weeks 1, 2, 3, 4, 8 and 3 month follow-up and 6 month follow-up
Gastrointestinal disorders Abdominal Pain	1.2% 1/80 • Number of events 1 • Adverse events were collected at weeks 1, 2, 3, 4, 8 and 3 month follow-up and 6 month follow-up	1.3% 1/79 • Number of events 1 • Adverse events were collected at weeks 1, 2, 3, 4, 8 and 3 month follow-up and 6 month follow-up
Musculoskeletal and connective tissue disorders Chest pain, non-cardiac	1.2% 1/80 • Number of events 1 • Adverse events were collected at weeks 1, 2, 3, 4, 8 and 3 month follow-up and 6 month follow-up	3.8% 3/79 • Number of events 3 • Adverse events were collected at weeks 1, 2, 3, 4, 8 and 3 month follow-up and 6 month follow-up
Vascular disorders Critical Limb Ischemia	1.2% 1/80 • Number of events 1 • Adverse events were collected at weeks 1, 2, 3, 4, 8 and 3 month follow-up and 6 month follow-up	0.00% 0/79 • Adverse events were collected at weeks 1, 2, 3, 4, 8 and 3 month follow-up and 6 month follow-up
Respiratory, thoracic and mediastinal disorders COPD Exacerbation	1.2% 1/80 • Number of events 1 • Adverse events were collected at weeks 1, 2, 3, 4, 8 and 3 month follow-up and 6 month follow-up	0.00% 0/79 • Adverse events were collected at weeks 1, 2, 3, 4, 8 and 3 month follow-up and 6 month follow-up
Surgical and medical procedures Elective Procedure	1.2% 1/80 • Number of events 1 • Adverse events were collected at weeks 1, 2, 3, 4, 8 and 3 month follow-up and 6 month follow-up	1.3% 1/79 • Number of events 1 • Adverse events were collected at weeks 1, 2, 3, 4, 8 and 3 month follow-up and 6 month follow-up
Cardiac disorders Heart Failure	0.00% 0/80 • Adverse events were collected at weeks 1, 2, 3, 4, 8 and 3 month follow-up and 6 month follow-up	1.3% 1/79 • Number of events 1 • Adverse events were collected at weeks 1, 2, 3, 4, 8 and 3 month follow-up and 6 month follow-up
Nervous system disorders Stroke	1.2% 1/80 • Number of events 1 • Adverse events were collected at weeks 1, 2, 3, 4, 8 and 3 month follow-up and 6 month follow-up	0.00% 0/79 • Adverse events were collected at weeks 1, 2, 3, 4, 8 and 3 month follow-up and 6 month follow-up
Gastrointestinal disorders Small Bowel Obstruction	0.00% 0/80 • Adverse events were collected at weeks 1, 2, 3, 4, 8 and 3 month follow-up and 6 month follow-up	1.3% 1/79 • Number of events 1 • Adverse events were collected at weeks 1, 2, 3, 4, 8 and 3 month follow-up and 6 month follow-up
Musculoskeletal and connective tissue disorders Trauma	0.00% 0/80 • Adverse events were collected at weeks 1, 2, 3, 4, 8 and 3 month follow-up and 6 month follow-up	1.3% 1/79 • Number of events 1 • Adverse events were collected at weeks 1, 2, 3, 4, 8 and 3 month follow-up and 6 month follow-up

Other adverse events

Measure	GM-CSF n=80 participants at risk Granulocyte-Macrophage Colony Stimulating Factor injection - Monday, Wednesday and Friday for 4 weeks of therapy. 500 microgram dose of GM-CSF	Placebo n=79 participants at risk Saline injection - Monday, Wednesday and Friday for 4 weeks.
Nervous system disorders Headaches	22.5% 18/80 • Number of events 18 • Adverse events were collected at weeks 1, 2, 3, 4, 8 and 3 month follow-up and 6 month follow-up	11.4% 9/79 • Number of events 9 • Adverse events were collected at weeks 1, 2, 3, 4, 8 and 3 month follow-up and 6 month follow-up
Cardiac disorders Difficulty breathing	6.2% 5/80 • Number of events 5 • Adverse events were collected at weeks 1, 2, 3, 4, 8 and 3 month follow-up and 6 month follow-up	10.1% 8/79 • Number of events 8 • Adverse events were collected at weeks 1, 2, 3, 4, 8 and 3 month follow-up and 6 month follow-up
Cardiac disorders Chest pain	7.5% 6/80 • Number of events 6 • Adverse events were collected at weeks 1, 2, 3, 4, 8 and 3 month follow-up and 6 month follow-up	8.9% 7/79 • Number of events 7 • Adverse events were collected at weeks 1, 2, 3, 4, 8 and 3 month follow-up and 6 month follow-up
Musculoskeletal and connective tissue disorders Joint/back/muscle pain	22.5% 18/80 • Number of events 18 • Adverse events were collected at weeks 1, 2, 3, 4, 8 and 3 month follow-up and 6 month follow-up	17.7% 14/79 • Number of events 14 • Adverse events were collected at weeks 1, 2, 3, 4, 8 and 3 month follow-up and 6 month follow-up
Gastrointestinal disorders Gastrointestinal side effects	26.2% 21/80 • Number of events 21 • Adverse events were collected at weeks 1, 2, 3, 4, 8 and 3 month follow-up and 6 month follow-up	13.9% 11/79 • Number of events 11 • Adverse events were collected at weeks 1, 2, 3, 4, 8 and 3 month follow-up and 6 month follow-up
General disorders Night sweats	16.2% 13/80 • Number of events 13 • Adverse events were collected at weeks 1, 2, 3, 4, 8 and 3 month follow-up and 6 month follow-up	7.6% 6/79 • Number of events 6 • Adverse events were collected at weeks 1, 2, 3, 4, 8 and 3 month follow-up and 6 month follow-up
Skin and subcutaneous tissue disorders Rash	51.2% 41/80 • Number of events 41 • Adverse events were collected at weeks 1, 2, 3, 4, 8 and 3 month follow-up and 6 month follow-up	1.3% 1/79 • Number of events 1 • Adverse events were collected at weeks 1, 2, 3, 4, 8 and 3 month follow-up and 6 month follow-up
Musculoskeletal and connective tissue disorders Swelling	11.2% 9/80 • Number of events 9 • Adverse events were collected at weeks 1, 2, 3, 4, 8 and 3 month follow-up and 6 month follow-up	5.1% 4/79 • Number of events 4 • Adverse events were collected at weeks 1, 2, 3, 4, 8 and 3 month follow-up and 6 month follow-up
General disorders Fatigue	21.2% 17/80 • Number of events 17 • Adverse events were collected at weeks 1, 2, 3, 4, 8 and 3 month follow-up and 6 month follow-up	11.4% 9/79 • Number of events 9 • Adverse events were collected at weeks 1, 2, 3, 4, 8 and 3 month follow-up and 6 month follow-up

Additional Information

Dr. Arshed Quyyumi

Emory University School of Medicine

Phone: 4047273655

Email: aquyyum@emory.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place