Electrical Stimulation for the Treatment of Post-Amputation Pain Using the SPRINT System

Study Overview
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Brief Summary
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The purpose of this study is to determine if electrical stimulation (small levels of electricity) can safely and effectively reduce post-amputation pain. This study involves a device called the SPRINT System. The SPRINT System delivers mild electrical stimulation to nerves in the residual limb. The SPRINT System includes a small wire (called a lead) that is placed through the skin in the upper leg. It also includes a device worn on the body that delivers stimulation (called the SPRINT Stimulator).

Official Title
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A Randomized, Double-Blinded, Placebo-Controlled, Multicenter Pilot Study of the SPRINT Peripheral Nerve Stimulation (PNS) System for the Treatment of Post-Amputation Pain

Conditions
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Post-Amputation Pain, Phantom Limb Pain, Residual Limb Pain

Intervention / Treatment
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* Device: SPRINT Peripheral Nerve Stimulation (PNS) System


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: At least 18 years old Traumatic lower extremity amputation(s) Healed amputation and healthy residual limb based upon the investigator's evaluation Key Exclusion Criteria: Change of prescribed medications affecting pain within the past 4 weeks Compromised immune system based on medical history Implanted electronic device Bleeding disorder History of valvular heart disease Confounding central nervous system injuries and disorders History of recurrent skin infections

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SPRINT Group 1<br>Subjects in Group 1 will have a Lead placed in the residual limb in the upper leg. These subjects will then use the SPRINT Peripheral Nerve Stimulation (PNS) System and will receive electrical stimulation for 8 weeks. | Device: SPRINT Peripheral Nerve Stimulation (PNS) System<br>* The SPRINT System is an Investigational Device which delivers mild electrical stimulation to nerves in the residual limb. The SPRINT System includes a small wire (called a Lead) that is placed through the skin in the upper leg. It also includes a device worn on the body that delivers stimulation (called the SPRINT Stimulator).<br>* Other names: Smartpatch System, Smartpatch;|
| Sham Comparator: SPRINT Group 2<br>Subjects in Group 2 will have a Lead placed in the residual limb in the upper leg. These subjects will then use the SPRINT Peripheral Nerve Stimulation (PNS) System for a total of 8 weeks. They will receive 4 weeks of stimulation and 4 weeks with no stimulation. | Device: SPRINT Peripheral Nerve Stimulation (PNS) System<br>* The SPRINT System is an Investigational Device which delivers mild electrical stimulation to nerves in the residual limb. The SPRINT System includes a small wire (called a Lead) that is placed through the skin in the upper leg. It also includes a device worn on the body that delivers stimulation (called the SPRINT Stimulator).<br>* Other names: Smartpatch System, Smartpatch;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects That Experienced at Least One Study-Related Adverse Event in Treatment and Control Groups | 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. | 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. | 
| 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 | 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. | Baseline and Weeks 1-4 Post-Start of Treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subject Satisfaction Survey | 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. | Visit 11 (8-weeks post-Start of Treatment (SOT)) | 
| 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 | 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. | Baseline and Weeks 1-8 Post-Start of Treatment | 
| Proportion of Subjects That Experienced ≥ 50% Reduction in All Qualifying Areas of Pain at Months 3-12 Post-Start of Treatment | 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. | 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 | 
| Proportion of Subjects That Experienced ≥50% Reduction in Average Pain Interference With Daily Activities | 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. | 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 | 
| 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 | 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. | 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 | 
| Depression at Monthly Intervals After Start of Therapy | 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. | 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 | 
| Change in Opioid Analgesic Usage From Baseline | 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. | Baseline, 4-weeks Post-Start of Treatment (SOT), and 8-weeks Post-SOT | 
| Percent Change in Hours of Daily Prosthetic Usage | 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. | Baseline, 4-weeks Post-Start of Treatment (SOT), and 8-weeks Post-SOT | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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electrical stimulation, neurostimulation, neuromodulation, post-amputation pain, phantom limb pain, residual limb pain, neuropathic pain, amputee pain