Trial Outcomes & Findings for Electrical Stimulation for the Treatment of Post-Amputation Pain Using the SPRINT System (NCT NCT01996254)

NCT ID: NCT01996254

Last Updated: 2020-03-26

Results Overview

Subjects completed daily diaries to record their average daily pain intensity scores for each qualifying region of pain (phantom limb pain and/or residual limb pain). These pain intensity questions were excerpted from the Brief Pain Inventory - Short Form Question 5 (BPI-5). The BPI-5 is an 11-point numerical rating scale where 0 represents "No Pain" and 10 represents "Pain as bad as you can imagine." Post-amputation pain intensity scores were determined for each subject by taking the mean of the daily average pain intensity scores from their diaries at Baseline compared to the mean score for the same region(s) of pain reported over 4 weeks after the Start of Treatment (i.e., the average of all diary scores during this period). Subjects that achieved ≥ 50% reduction in their qualifying area(s) of pain were considered successful. Missing diary data were replaced using 1-week BPI-5 recall; if recall scores were unavailable, baseline values were imputed.

Recruitment status

COMPLETED

Study phase

Target enrollment

28 participants

Primary outcome timeframe

Baseline and Weeks 1-4 Post-Start of Treatment

Results posted on

2020-03-26

Participant Flow

Recruitment began in 10-2013 (with the first subject enrolling 12-2013) and was concluded in 05-2018. Subjects were screened from a pool of candidates experiencing chronic post-amputation pain.

Participants in the Initial Study Design Arm were only assessed for Safety (Adverse Events).

Participant milestones

Participant milestones
Measure	Initial Study Design Subjects Subjects who were consented and enrolled under the initial design of the study. These subjects are included in the Safety Set.	Group 1 (Treatment Group, Revised Study Design) Treatment Group subjects were consented and enrolled under the revised study design. These subjects had at least one Lead placed and received electrical stimulation therapy.	Group 2 (Control Group, Revised Study Design) Control Group subjects were consented and enrolled under the revised study design. These subjects had at least one Lead placed and received sham stimulation therapy.
Overall Study STARTED	5	14	14
Overall Study Safety Set	5	14	14
Overall Study Full Analysis Set	0	12	14
Overall Study Long Term Analysis Set	0	12	14
Overall Study Per Protocol Set	0	10	13
Overall Study COMPLETED	4	9	6
Overall Study NOT COMPLETED	1	5	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Initial Study Design Subjects Subjects who were consented and enrolled under the initial design of the study. These subjects are included in the Safety Set.	Group 1 (Treatment Group, Revised Study Design) Treatment Group subjects were consented and enrolled under the revised study design. These subjects had at least one Lead placed and received electrical stimulation therapy.	Group 2 (Control Group, Revised Study Design) Control Group subjects were consented and enrolled under the revised study design. These subjects had at least one Lead placed and received sham stimulation therapy.
Overall Study Change in Eligibility	0	2	0
Overall Study Withdrawal by Subject	0	3	4
Overall Study Lost to Follow-up	1	0	4

Baseline Characteristics

Height was not collected for 1 of the 12 (Group 1) participants so BMI was not able to be calculated for that participant. This accounts for the difference in number analyzed in this row from the 26 overall.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group 1 (Treatment Group, Revised Study Design) n=12 Participants Treatment Group subjects were consented and enrolled under the revised study design. These subjects had at least one Lead placed and received electrical stimulation therapy.	Group 2 (Control Group, Revised Study Design) n=14 Participants Control Group subjects were consented and enrolled under the revised study design. These subjects had at least one Lead placed and received sham stimulation therapy.	Total n=26 Participants Total of all reporting groups
Age, Continuous	48.3 Years STANDARD_DEVIATION 12.3 • n=12 Participants	45.0 Years STANDARD_DEVIATION 13.2 • n=14 Participants	46.5 Years STANDARD_DEVIATION 12.7 • n=26 Participants
Sex: Female, Male Female	2 Participants n=12 Participants	4 Participants n=14 Participants	6 Participants n=26 Participants
Sex: Female, Male Male	10 Participants n=12 Participants	10 Participants n=14 Participants	20 Participants n=26 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=12 Participants	1 Participants n=14 Participants	1 Participants n=26 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants n=12 Participants	13 Participants n=14 Participants	25 Participants n=26 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=12 Participants	0 Participants n=14 Participants	0 Participants n=26 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=12 Participants	0 Participants n=14 Participants	0 Participants n=26 Participants
Race (NIH/OMB) Asian	0 Participants n=12 Participants	0 Participants n=14 Participants	0 Participants n=26 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=12 Participants	0 Participants n=14 Participants	0 Participants n=26 Participants
Race (NIH/OMB) Black or African American	1 Participants n=12 Participants	0 Participants n=14 Participants	1 Participants n=26 Participants
Race (NIH/OMB) White	11 Participants n=12 Participants	14 Participants n=14 Participants	25 Participants n=26 Participants
Race (NIH/OMB) More than one race	0 Participants n=12 Participants	0 Participants n=14 Participants	0 Participants n=26 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=12 Participants	0 Participants n=14 Participants	0 Participants n=26 Participants
Body Mass Index	26.5 kg per square meter n=11 Participants • Height was not collected for 1 of the 12 (Group 1) participants so BMI was not able to be calculated for that participant. This accounts for the difference in number analyzed in this row from the 26 overall.	30.8 kg per square meter n=14 Participants • Height was not collected for 1 of the 12 (Group 1) participants so BMI was not able to be calculated for that participant. This accounts for the difference in number analyzed in this row from the 26 overall.	27.4 kg per square meter n=25 Participants • Height was not collected for 1 of the 12 (Group 1) participants so BMI was not able to be calculated for that participant. This accounts for the difference in number analyzed in this row from the 26 overall.
Time Since Amputation	5.7 Years n=12 Participants	4.8 Years n=14 Participants	5.0 Years n=26 Participants
Baseline Beck Depression Inventory Score	6.5 units on a scale n=12 Participants	12.5 units on a scale n=14 Participants	11.0 units on a scale n=26 Participants
Location of Amputation Above Knee	10 Participants n=12 Participants	5 Participants n=14 Participants	15 Participants n=26 Participants
Location of Amputation Below Knee	2 Participants n=12 Participants	9 Participants n=14 Participants	11 Participants n=26 Participants
Side of Amputation Left Side	8 Participants n=12 Participants	6 Participants n=14 Participants	14 Participants n=26 Participants
Side of Amputation Right Side	3 Participants n=12 Participants	7 Participants n=14 Participants	10 Participants n=26 Participants
Side of Amputation Both Sides (Bilateral)	1 Participants n=12 Participants	1 Participants n=14 Participants	2 Participants n=26 Participants

PRIMARY outcome

Timeframe: Baseline and Weeks 1-4 Post-Start of Treatment

Population: Full Analysis Set: Subjects who were consented, randomized, and met all eligibility criteria prior to Lead placement

Outcome measures

Outcome measures
Measure	Group 1 (Treatment Group, Revised Study Design) n=12 Participants Treatment Group subjects were consented and enrolled under the revised study design. These subjects had at least one Lead placed and received electrical stimulation therapy.	Group 2 (Control Group, Revised Study Design) n=14 Participants Control Group subjects were consented and enrolled under the revised study design. These subjects had at least one Lead placed and received sham stimulation therapy.	Group 2 (Control Group, Revised Study Design) Control Group subjects were consented and enrolled under the revised study design. These subjects had at least one Lead placed and received sham stimulation therapy.
Proportion of Group 1 (Treatment) and Group 2 (Control) Subjects That Achieved ≥ 50% Reduction in All Qualifying Areas of Pain in the First 4 Weeks of Treatment	7 Participants	2 Participants	—

PRIMARY outcome

Timeframe: Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.

Population: Safety Set: All subjects that underwent Lead placement.

At each study visit following the baseline assessment at Visit 1, subjects were questioned if any changes in their medical status or condition had occurred since their previous visit. If the subject experienced a change that was an adverse event, an Adverse Event Form was completed by the site. The number of subjects that experienced at least one study-related adverse event is reported here.

Outcome measures

Outcome measures
Measure	Group 1 (Treatment Group, Revised Study Design) n=5 Participants Treatment Group subjects were consented and enrolled under the revised study design. These subjects had at least one Lead placed and received electrical stimulation therapy.	Group 2 (Control Group, Revised Study Design) n=14 Participants Control Group subjects were consented and enrolled under the revised study design. These subjects had at least one Lead placed and received sham stimulation therapy.	Group 2 (Control Group, Revised Study Design) n=14 Participants Control Group subjects were consented and enrolled under the revised study design. These subjects had at least one Lead placed and received sham stimulation therapy.
Number of Subjects That Experienced at Least One Study-Related Adverse Event in Treatment and Control Groups	0 Participants	5 Participants	8 Participants

SECONDARY outcome

Timeframe: Baseline and Weeks 1-8 Post-Start of Treatment

Population: Full Analysis Set: Subjects from the Revised Study Design that enrolled and met all eligibility prior to Lead placement.

Subjects completed daily diaries to record their average daily pain intensity scores for each qualifying region of pain (phantom limb pain and/or residual limb pain). These pain intensity questions were excerpted from the Brief Pain Inventory - Short Form Question 5 (BPI-5) on a scale from 0 to 10, where 0 indicates no pain and 10 indicates pain as bad as you can imagine. Post-amputation pain intensity scores were determined by taking the mean of the daily average pain intensity scores at baseline and over weeks 5-8 post-start of treatment for Group 1 subjects and over weeks 1-4 post-start of treatment for Group 2 subjects. Subjects that achieved ≥ 50% reduction in their qualifying area(s) of pain were considered successful. Missing diary data were replaced using the bi-weekly BPI-5 recall scores; if unavailable, the BPI-5 recall from the follow-up visit was used. The number of successes in each group is reported.

Outcome measures

Outcome measures
Measure	Group 1 (Treatment Group, Revised Study Design) n=12 Participants Treatment Group subjects were consented and enrolled under the revised study design. These subjects had at least one Lead placed and received electrical stimulation therapy.	Group 2 (Control Group, Revised Study Design) n=14 Participants Control Group subjects were consented and enrolled under the revised study design. These subjects had at least one Lead placed and received sham stimulation therapy.	Group 2 (Control Group, Revised Study Design) Control Group subjects were consented and enrolled under the revised study design. These subjects had at least one Lead placed and received sham stimulation therapy.
Number of Group 1 (Treatment) Subjects That Experienced ≥ 50% Reduction in All Qualifying Areas of Pain During Weeks 5-8 Compared to Group 2 (Control) Subjects During Weeks 1-4	8 Participants	2 Participants	—

SECONDARY outcome

Timeframe: 3-months Post-SOT, 4-months Post-SOT, 5-months Post-SOT, 6-months Post-SOT, 7-months Post-SOT, 8-months Post-SOT, 9-months Post-SOT, 10-months Post-SOT, 11-months Post-SOT, and 12-months Post-SOT

Population: Long Term Analysis Set: Subjects from the Revised Study Design that enrolled and met all eligibility prior to Lead placement with imputed data for missed visits. Covarities in the imputation model included age, gender, ethnicity, race, time since amputation, location of amputation, and baseline average pain intensity score(s).

Subjects were asked to recall and rate their average pain intensity over the past week (BPI-SF question 5) for each qualifying area of pain (phantom and/or residual limb pain) on a scale from 0 to 10, where 0 indicates no pain and 10 indicates pain as bad as you can imagine. The average pain intensity score(s) at baseline were compared to the same region(s) of pain at monthly intervals from months 3-12 post-start of treatment (SOT). Subjects that achieved ≥ 50% reduction in their qualifying area(s) of pain were considered successful. Certain time points for Group 2 (i.e., after crossover) were considered exploratory, but are reported with this outcome measure for ease of data entry and readability.

Outcome measures

Outcome measures
Measure	Group 1 (Treatment Group, Revised Study Design) n=12 Participants Treatment Group subjects were consented and enrolled under the revised study design. These subjects had at least one Lead placed and received electrical stimulation therapy.	Group 2 (Control Group, Revised Study Design) n=14 Participants Control Group subjects were consented and enrolled under the revised study design. These subjects had at least one Lead placed and received sham stimulation therapy.	Group 2 (Control Group, Revised Study Design) Control Group subjects were consented and enrolled under the revised study design. These subjects had at least one Lead placed and received sham stimulation therapy.
Proportion of Subjects That Experienced ≥ 50% Reduction in All Qualifying Areas of Pain at Months 3-12 Post-Start of Treatment 3-months Post-Start of Treatment	5 Participants	0 Participants	—
Proportion of Subjects That Experienced ≥ 50% Reduction in All Qualifying Areas of Pain at Months 3-12 Post-Start of Treatment 4-months Post-Start of Treatment	7 Participants	1 Participants	—
Proportion of Subjects That Experienced ≥ 50% Reduction in All Qualifying Areas of Pain at Months 3-12 Post-Start of Treatment 5-months Post-Start of Treatment	5 Participants	0 Participants	—
Proportion of Subjects That Experienced ≥ 50% Reduction in All Qualifying Areas of Pain at Months 3-12 Post-Start of Treatment 6-months Post-Start of Treatment	4 Participants	0 Participants	—
Proportion of Subjects That Experienced ≥ 50% Reduction in All Qualifying Areas of Pain at Months 3-12 Post-Start of Treatment 7-months Post-Start of Treatment	5 Participants	0 Participants	—
Proportion of Subjects That Experienced ≥ 50% Reduction in All Qualifying Areas of Pain at Months 3-12 Post-Start of Treatment 8-months Post-Start of Treatment	6 Participants	0 Participants	—
Proportion of Subjects That Experienced ≥ 50% Reduction in All Qualifying Areas of Pain at Months 3-12 Post-Start of Treatment 9-months Post-Start of Treatment	6 Participants	0 Participants	—
Proportion of Subjects That Experienced ≥ 50% Reduction in All Qualifying Areas of Pain at Months 3-12 Post-Start of Treatment 10-months Post-Start of Treatment	5 Participants	0 Participants	—
Proportion of Subjects That Experienced ≥ 50% Reduction in All Qualifying Areas of Pain at Months 3-12 Post-Start of Treatment 11-months Post-Start of Treatment	6 Participants	0 Participants	—
Proportion of Subjects That Experienced ≥ 50% Reduction in All Qualifying Areas of Pain at Months 3-12 Post-Start of Treatment 12-months Post-Start of Treatment	6 Participants	1 Participants	—

SECONDARY outcome

Timeframe: Baseline, 4-weeks Post-Start of Treatment (SOT), 8-weeks Post-SOT, 3-months Post-SOT, 4-months Post-SOT, 5-months Post-SOT, 6-months Post-SOT, 7-months Post-SOT, 8-months Post-SOT, 9-months Post-SOT, 10-months Post-SOT, 11-mo Post-SOT, & 12-mo Post-SOT

Degree of post-amputation pain that interfered with 7 aspects of daily life was rated \[scale (0 to 10) with higher scores indicating greater interference\]. The 7 individual scores were averaged to provide an overall pain interference score. Pain interference questions (Brief Pain Inventory - Short Form Question 9) were used for each qualifying area of pain (phantom and/or residual limb pain). Group 1 subjects: baseline average pain interference scores were compared to average pain interference scores for the same region(s) of pain at each monthly interval after the start of therapy. Group 2 subjects: baseline average pain interference scores were compared to their average score at the end of 4 weeks. Proportion of successes (subjects that experienced ≥50% reduction in average pain interference scores) is reported. Certain time points for Group 2 (i.e., after crossover) were considered exploratory but are being reported here for ease of data entry and readability.

Outcome measures

Outcome measures
Measure	Group 1 (Treatment Group, Revised Study Design) n=12 Participants Treatment Group subjects were consented and enrolled under the revised study design. These subjects had at least one Lead placed and received electrical stimulation therapy.	Group 2 (Control Group, Revised Study Design) n=14 Participants Control Group subjects were consented and enrolled under the revised study design. These subjects had at least one Lead placed and received sham stimulation therapy.	Group 2 (Control Group, Revised Study Design) Control Group subjects were consented and enrolled under the revised study design. These subjects had at least one Lead placed and received sham stimulation therapy.
Proportion of Subjects That Experienced ≥50% Reduction in Average Pain Interference With Daily Activities 4-weeks Post-Start of Treatment	6 Participants	2 Participants	—
Proportion of Subjects That Experienced ≥50% Reduction in Average Pain Interference With Daily Activities 8-weeks Post-Start of Treatment	9 Participants	2 Participants	—
Proportion of Subjects That Experienced ≥50% Reduction in Average Pain Interference With Daily Activities 3-months Post-Start of Treatment	6 Participants	2 Participants	—
Proportion of Subjects That Experienced ≥50% Reduction in Average Pain Interference With Daily Activities 4-months Post-Start of Treatment	7 Participants	4 Participants	—
Proportion of Subjects That Experienced ≥50% Reduction in Average Pain Interference With Daily Activities 5-months Post-Start of Treatment	7 Participants	2 Participants	—
Proportion of Subjects That Experienced ≥50% Reduction in Average Pain Interference With Daily Activities 6-months Post-Start of Treatment	5 Participants	2 Participants	—
Proportion of Subjects That Experienced ≥50% Reduction in Average Pain Interference With Daily Activities 7-months Post-Start of Treatment	6 Participants	2 Participants	—
Proportion of Subjects That Experienced ≥50% Reduction in Average Pain Interference With Daily Activities 8-months Post-Start of Treatment	5 Participants	0 Participants	—
Proportion of Subjects That Experienced ≥50% Reduction in Average Pain Interference With Daily Activities 9-months Post-Start of Treatment	5 Participants	0 Participants	—
Proportion of Subjects That Experienced ≥50% Reduction in Average Pain Interference With Daily Activities 10-months Post-Start of Treatment	5 Participants	2 Participants	—
Proportion of Subjects That Experienced ≥50% Reduction in Average Pain Interference With Daily Activities 11-months Post-Start of Treatment	5 Participants	2 Participants	—
Proportion of Subjects That Experienced ≥50% Reduction in Average Pain Interference With Daily Activities 12-months Post-Start of Treatment	5 Participants	2 Participants	—

SECONDARY outcome

Population: Full Analysis Set: Subjects from the Revised Study Design that enrolled and met all eligibility prior to Lead placement.

The Pain Disability Index (PDI) is a validated survey measuring the degree pain disrupts 7 categories of life activities on a scale from 0 to 10, with higher scores indicating greater disability. The 7 scores were summed for each subject to provide an overall pain disability score. For Group 1 subjects, the baseline average PDI score was compared to PDI scores at monthly intervals. For Group 2 subjects, the baseline average PDI score was compared to their PDI score at the end of 4 weeks. The proportion of successes (subjects reporting ≥10 point reduction in PDI scores from baseline) are reported for Group 1 subjects. Certain time points for Group 2 (i.e., after crossover) were considered exploratory but are being reported within this outcome measure for ease of data entry and readability.

Outcome measures

Outcome measures
Measure	Group 1 (Treatment Group, Revised Study Design) n=12 Participants Treatment Group subjects were consented and enrolled under the revised study design. These subjects had at least one Lead placed and received electrical stimulation therapy.	Group 2 (Control Group, Revised Study Design) n=14 Participants Control Group subjects were consented and enrolled under the revised study design. These subjects had at least one Lead placed and received sham stimulation therapy.	Group 2 (Control Group, Revised Study Design) Control Group subjects were consented and enrolled under the revised study design. These subjects had at least one Lead placed and received sham stimulation therapy.
Proportion of Group 1 (Treatment) Subjects That Experienced ≥ 10-point Reduction in Pain Disability at Monthly Intervals Post-Start of Treatment Compared to Group 2 (Control) Subjects at Week 4 Post-Start of Treatment 4-weeks Post-Start of Treatment	6 Participants	10 Participants	—
Proportion of Group 1 (Treatment) Subjects That Experienced ≥ 10-point Reduction in Pain Disability at Monthly Intervals Post-Start of Treatment Compared to Group 2 (Control) Subjects at Week 4 Post-Start of Treatment 8-weeks Post-Start of Treatment	8 Participants	9 Participants	—
Proportion of Group 1 (Treatment) Subjects That Experienced ≥ 10-point Reduction in Pain Disability at Monthly Intervals Post-Start of Treatment Compared to Group 2 (Control) Subjects at Week 4 Post-Start of Treatment 3-months Post-Start of Treatment	7 Participants	7 Participants	—
Proportion of Group 1 (Treatment) Subjects That Experienced ≥ 10-point Reduction in Pain Disability at Monthly Intervals Post-Start of Treatment Compared to Group 2 (Control) Subjects at Week 4 Post-Start of Treatment 4-months Post-Start of Treatment	6 Participants	7 Participants	—
Proportion of Group 1 (Treatment) Subjects That Experienced ≥ 10-point Reduction in Pain Disability at Monthly Intervals Post-Start of Treatment Compared to Group 2 (Control) Subjects at Week 4 Post-Start of Treatment 5-months Post-Start of Treatment	7 Participants	6 Participants	—
Proportion of Group 1 (Treatment) Subjects That Experienced ≥ 10-point Reduction in Pain Disability at Monthly Intervals Post-Start of Treatment Compared to Group 2 (Control) Subjects at Week 4 Post-Start of Treatment 6-months Post-Start of Treatment	5 Participants	4 Participants	—
Proportion of Group 1 (Treatment) Subjects That Experienced ≥ 10-point Reduction in Pain Disability at Monthly Intervals Post-Start of Treatment Compared to Group 2 (Control) Subjects at Week 4 Post-Start of Treatment 7-months Post-Start of Treatment	6 Participants	4 Participants	—
Proportion of Group 1 (Treatment) Subjects That Experienced ≥ 10-point Reduction in Pain Disability at Monthly Intervals Post-Start of Treatment Compared to Group 2 (Control) Subjects at Week 4 Post-Start of Treatment 8-months Post-Start of Treatment	6 Participants	4 Participants	—
Proportion of Group 1 (Treatment) Subjects That Experienced ≥ 10-point Reduction in Pain Disability at Monthly Intervals Post-Start of Treatment Compared to Group 2 (Control) Subjects at Week 4 Post-Start of Treatment 9-months Post-Start of Treatment	5 Participants	4 Participants	—
Proportion of Group 1 (Treatment) Subjects That Experienced ≥ 10-point Reduction in Pain Disability at Monthly Intervals Post-Start of Treatment Compared to Group 2 (Control) Subjects at Week 4 Post-Start of Treatment 10-months Post-Start of Treatment	5 Participants	4 Participants	—
Proportion of Group 1 (Treatment) Subjects That Experienced ≥ 10-point Reduction in Pain Disability at Monthly Intervals Post-Start of Treatment Compared to Group 2 (Control) Subjects at Week 4 Post-Start of Treatment 11-months Post-Start of Treatment	5 Participants	4 Participants	—
Proportion of Group 1 (Treatment) Subjects That Experienced ≥ 10-point Reduction in Pain Disability at Monthly Intervals Post-Start of Treatment Compared to Group 2 (Control) Subjects at Week 4 Post-Start of Treatment 12-months Post-Start of Treatment	5 Participants	3 Participants	—

SECONDARY outcome

Population: Full Analysis Set: Subjects from the Revised Study Design that enrolled and met all eligibility prior to Lead placement.

The Beck Depression Inventory (BDI-II) is a validated, 21-question survey used to measure depression severity. Question are rated on a scale from 0 to 3, and the scores from each question are totaled to provide an overall score ranging between 0 to 63. Scores from 0-13 indicate minimal depression, 14-19 mild depression, 20-28 moderate depression, and 29-63 severe depression. Group 1 subjects: baseline BDI-II score was compared to BDI-II scores at monthly intervals. Group 2 subjects: baseline BDI-II score was compared to their BDI-II score at the end of 4 weeks. The percent change from baseline to each monthly interval is reported. Certain timepoints for Group 2 (i.e., after crossover) were considered exploratory but are being reported within this outcome measure for ease of data entry and readability.

Outcome measures

Outcome measures
Measure	Group 1 (Treatment Group, Revised Study Design) n=12 Participants Treatment Group subjects were consented and enrolled under the revised study design. These subjects had at least one Lead placed and received electrical stimulation therapy.	Group 2 (Control Group, Revised Study Design) n=14 Participants Control Group subjects were consented and enrolled under the revised study design. These subjects had at least one Lead placed and received sham stimulation therapy.	Group 2 (Control Group, Revised Study Design) Control Group subjects were consented and enrolled under the revised study design. These subjects had at least one Lead placed and received sham stimulation therapy.
Depression at Monthly Intervals After Start of Therapy 5-months Post-Start of Treatment	-75.00 percent change Interval -100.0 to 88.89	-47.06 percent change Interval -100.0 to 70.59	—
Depression at Monthly Intervals After Start of Therapy 7-months Post-Start of Treatment	-30.00 percent change Interval -100.0 to 50.0	11.76 percent change Interval -75.0 to 122.22	—
Depression at Monthly Intervals After Start of Therapy 6-months Post-Start of Treatment	-50.00 percent change Interval -100.0 to 22.22	22.22 percent change Interval -75.0 to 136.36	—
Depression at Monthly Intervals After Start of Therapy 4-weeks Post-Start of Treatment	-17.69 percent change Interval -100.0 to 50.0	-11.76 percent change Interval -91.67 to 136.36	—
Depression at Monthly Intervals After Start of Therapy 8-weeks Post-Start of Treatment	-50.00 percent change Interval -100.0 to 100.0	-15.38 percent change Interval -100.0 to 129.41	—
Depression at Monthly Intervals After Start of Therapy 3-months Post-Start of Treatment	-55.00 percent change Interval -100.0 to 177.78	-10.00 percent change Interval -50.0 to 154.55	—
Depression at Monthly Intervals After Start of Therapy 4-months Post-Start of Treatment	-75.00 percent change Interval -100.0 to 111.11	-35.29 percent change Interval -70.59 to 70.59	—
Depression at Monthly Intervals After Start of Therapy 8-months Post-Start of Treatment	-70.00 percent change Interval -100.0 to 50.0	-41.18 percent change Interval -50.0 to 90.91	—
Depression at Monthly Intervals After Start of Therapy 9-months Post-Start of Treatment	-68.75 percent change Interval -100.0 to 50.0	-17.65 percent change Interval -50.0 to 90.91	—
Depression at Monthly Intervals After Start of Therapy 10-months Post-Start of Treatment	-65.00 percent change Interval -100.0 to 25.0	-67.65 percent change Interval -75.0 to 90.91	—
Depression at Monthly Intervals After Start of Therapy 11-months Post-Start of Treatment	-80.00 percent change Interval -100.0 to 25.0	-69.85 percent change Interval -100.0 to 90.91	—
Depression at Monthly Intervals After Start of Therapy 12-months Post-Start of Treatment	0.00 percent change Interval -100.0 to 66.67	-72.79 percent change Interval -100.0 to 209.09	—

SECONDARY outcome

Timeframe: Baseline, 4-weeks Post-Start of Treatment (SOT), and 8-weeks Post-SOT

Population: Full Analysis Set: Subjects from the Revised Study Design that enrolled and met all eligibility prior to Lead placement. Only the 9 subjects that were using opioid analgesics at baseline were included in the analysis.

Changes in opioid analgesic usage were calculated using morphine equivalent dosing (MED) for subjects who were using opioid analgesics at baseline. Subjects completed daily diaries in which they tracked their use of analgesic medications. For Group 1 subjects, the mean daily MED from the baseline diary was compared to the mean daily MED during week 4 and week 8. For Group 2 subjects, the daily MED from the baseline diary was compared to the daily MED during week 4 only. The median percent change from baseline is reported. Certain time points for Group 2 (i.e., after crossover) were considered exploratory but are being reported within this outcome measure for ease of data entry and readability.

Outcome measures

Outcome measures
Measure	Group 1 (Treatment Group, Revised Study Design) n=12 Participants Treatment Group subjects were consented and enrolled under the revised study design. These subjects had at least one Lead placed and received electrical stimulation therapy.	Group 2 (Control Group, Revised Study Design) n=14 Participants Control Group subjects were consented and enrolled under the revised study design. These subjects had at least one Lead placed and received sham stimulation therapy.	Group 2 (Control Group, Revised Study Design) Control Group subjects were consented and enrolled under the revised study design. These subjects had at least one Lead placed and received sham stimulation therapy.
Change in Opioid Analgesic Usage From Baseline 4-Weeks Post-Start of Treatment	32.68 percent change Interval 26.32 to 100.0	47.17 percent change Interval -55.6 to 100.0	—
Change in Opioid Analgesic Usage From Baseline 8-Weeks Post-Start of Treatment	78.79 percent change Interval 26.32 to 100.0	45.28 percent change Interval -55.6 to 100.0	—

SECONDARY outcome

Timeframe: Baseline, 4-weeks Post-Start of Treatment (SOT), and 8-weeks Post-SOT

Population: Full Analysis Set: Subjects from the Revised Study Design that enrolled and met all eligibility prior to Lead placement.

Subjects completed daily diaries in which they tracked the number of hours of their prosthetic usage. The 7-day mean prosthetic use was calculated for each subject from their baseline diary and compared to the 7-day mean from week 4 and week 8. The percent change from baseline was then calculated for each subject at each time point (i.e., 4-week median vs. baseline median and 8-week median vs. baseline median). A positive value indicates an increase in prosthetic usage.

Outcome measures

Outcome measures
Measure	Group 1 (Treatment Group, Revised Study Design) n=12 Participants Treatment Group subjects were consented and enrolled under the revised study design. These subjects had at least one Lead placed and received electrical stimulation therapy.	Group 2 (Control Group, Revised Study Design) n=14 Participants Control Group subjects were consented and enrolled under the revised study design. These subjects had at least one Lead placed and received sham stimulation therapy.	Group 2 (Control Group, Revised Study Design) Control Group subjects were consented and enrolled under the revised study design. These subjects had at least one Lead placed and received sham stimulation therapy.
Percent Change in Hours of Daily Prosthetic Usage 4-weeks Post-Start of Treatment	2.49 percent change Interval -19.1 to 28.89	4.51 percent change Interval -20.0 to 95.52	—
Percent Change in Hours of Daily Prosthetic Usage 8-weeks Post-Start of Treatment	3.23 percent change Interval -5.75 to 20.0	9.14 percent change Interval -19.11 to 82.84	—

SECONDARY outcome

Timeframe: Visit 11 (8-weeks post-Start of Treatment (SOT))

Population: Of the 28 total subjects, 14 subjects that used one version of the stimulator (Sprint Beta) were asked to complete subject surveys and 6 of the 14 responded. Results are presented for the 6 surveys.

Subjects completed a sponsor-developed survey with questions pertaining to their feelings about therapy as delivered by the SPRINT Beta Stimulation System as a method for managing chronic post-amputation pain. Subjects were asked to report on their experience using the therapy. Depending on the question, subjects were asked to indicate their agreement with the question (strongly disagree, agree, neutral, disagree, strongly disagree), their comfort with the therapy (very uncomfortable, a little bit uncomfortable, fairly comfortable, very comfortable), or when pain relief was felt (immediately, a few minutes later, a few hours later, more than a day later or never). Responses are presented for key groups of questions related to the therapy whereby answer options are considered affirmative for strongly agree/agree, very easy/easy, very comfortable/comfortable.

Outcome measures

Outcome measures
Measure	Group 1 (Treatment Group, Revised Study Design) n=3 Participants Treatment Group subjects were consented and enrolled under the revised study design. These subjects had at least one Lead placed and received electrical stimulation therapy.	Group 2 (Control Group, Revised Study Design) n=3 Participants Control Group subjects were consented and enrolled under the revised study design. These subjects had at least one Lead placed and received sham stimulation therapy.	Group 2 (Control Group, Revised Study Design) Control Group subjects were consented and enrolled under the revised study design. These subjects had at least one Lead placed and received sham stimulation therapy.
Subject Satisfaction Survey Pain relief (w/stim) immediate/within a few hours	3 Participants	3 Participants	—
Subject Satisfaction Survey Stimulation felt comfortable/soothing/tolerable	3 Participants	3 Participants	—
Subject Satisfaction Survey Prefer stimulation to pain medications	3 Participants	3 Participants	—
Subject Satisfaction Survey Would recommend therapy	3 Participants	2 Participants	—
Subject Satisfaction Survey Tolerated lead placement w/some or no discomfort	3 Participants	3 Participants	—
Subject Satisfaction Survey Would like to have used stimulation longer	3 Participants	2 Participants	—

Adverse Events

Initial Study Design Subjects

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Group 1 (Treatment Group, Revised Study Design)

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

Group 2 (Control Group, Revised Study Design)

Serious events: 1 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Initial Study Design Subjects n=5 participants at risk Subjects who were consented and enrolled under the initial design of the study.	Group 1 (Treatment Group, Revised Study Design) n=14 participants at risk Treatment Group subjects were consented and enrolled under the revised study design. These subjects had at least one Lead placed and received electrical stimulation therapy.	Group 2 (Control Group, Revised Study Design) n=14 participants at risk Control Group subjects were consented and enrolled under the revised study design. These subjects had at least one Lead placed and received sham stimulation therapy.
Social circumstances Car accident	20.0% 1/5 • Number of events 1 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.	0.00% 0/14 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.	0.00% 0/14 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.
Musculoskeletal and connective tissue disorders Patellar Fracture	0.00% 0/5 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.	0.00% 0/14 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.	7.1% 1/14 • Number of events 1 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.
Gastrointestinal disorders Gallstones	0.00% 0/5 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.	7.1% 1/14 • Number of events 1 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.	0.00% 0/14 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.
Nervous system disorders Leg Pain/Neuropathy	0.00% 0/5 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.	7.1% 1/14 • Number of events 1 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.	0.00% 0/14 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.
Musculoskeletal and connective tissue disorders Pleuritic Pain	0.00% 0/5 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.	7.1% 1/14 • Number of events 1 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.	0.00% 0/14 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.

Other adverse events

Additional Information

Clinical Affairs

SPR Therapeutics, Inc.

Phone: 216-378-9108

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER

Measure	Initial Study Design Subjects n=5 participants at risk Subjects who were consented and enrolled under the initial design of the study.	Group 1 (Treatment Group, Revised Study Design) n=14 participants at risk Treatment Group subjects were consented and enrolled under the revised study design. These subjects had at least one Lead placed and received electrical stimulation therapy.	Group 2 (Control Group, Revised Study Design) n=14 participants at risk Control Group subjects were consented and enrolled under the revised study design. These subjects had at least one Lead placed and received sham stimulation therapy.
Gastrointestinal disorders Diarrhea	0.00% 0/5 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.	7.1% 1/14 • Number of events 1 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.	7.1% 1/14 • Number of events 1 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.
Gastrointestinal disorders Nausea	0.00% 0/5 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.	7.1% 1/14 • Number of events 1 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.	0.00% 0/14 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.
General disorders Tiredness/Fatigue	0.00% 0/5 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.	7.1% 1/14 • Number of events 2 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.	0.00% 0/14 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.
General disorders Cold/Flu/Sinus infection	0.00% 0/5 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.	7.1% 1/14 • Number of events 1 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.	7.1% 1/14 • Number of events 1 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.
General disorders Pain	0.00% 0/5 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.	0.00% 0/14 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.	7.1% 1/14 • Number of events 1 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.
Musculoskeletal and connective tissue disorders Broken bone	0.00% 0/5 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.	0.00% 0/14 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.	7.1% 1/14 • Number of events 1 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/5 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.	0.00% 0/14 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.	7.1% 1/14 • Number of events 1 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.
Product Issues Pain and tenderness from procedure	0.00% 0/5 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.	0.00% 0/14 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.	21.4% 3/14 • Number of events 3 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.
Product Issues Unpleasant painful stimulation	0.00% 0/5 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.	14.3% 2/14 • Number of events 2 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.	0.00% 0/14 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.
Renal and urinary disorders Urinary tract infection	0.00% 0/5 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.	0.00% 0/14 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.	7.1% 1/14 • Number of events 1 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.
Respiratory, thoracic and mediastinal disorders Bronchitis	0.00% 0/5 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.	7.1% 1/14 • Number of events 1 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.	7.1% 1/14 • Number of events 1 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.
Respiratory, thoracic and mediastinal disorders Upper respiratory infection	0.00% 0/5 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.	14.3% 2/14 • Number of events 2 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.	0.00% 0/14 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.
Skin and subcutaneous tissue disorders Itching irritation or bruising from SPRINT pads	0.00% 0/5 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.	7.1% 1/14 • Number of events 1 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.	14.3% 2/14 • Number of events 2 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.
Skin and subcutaneous tissue disorders Skin irritation/redness at Lead exit site	0.00% 0/5 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.	21.4% 3/14 • Number of events 3 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.	21.4% 3/14 • Number of events 3 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.
Skin and subcutaneous tissue disorders Itching or irritation from bandages and/or belt	0.00% 0/5 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.	7.1% 1/14 • Number of events 1 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.	21.4% 3/14 • Number of events 4 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.
Skin and subcutaneous tissue disorders Non-specified skin irritation	0.00% 0/5 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.	7.1% 1/14 • Number of events 1 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.	7.1% 1/14 • Number of events 1 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.
Skin and subcutaneous tissue disorders Blister/abcess	0.00% 0/5 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.	7.1% 1/14 • Number of events 1 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.	7.1% 1/14 • Number of events 1 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.
Surgical and medical procedures Surgery	0.00% 0/5 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.	7.1% 1/14 • Number of events 2 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.	7.1% 1/14 • Number of events 1 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.
Social circumstances Fall	0.00% 0/5 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.	7.1% 1/14 • Number of events 1 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.	7.1% 1/14 • Number of events 1 • Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.