The SNAP Trial: SPRINT® Peripheral Nerve Stimulation for the Treatment of Neuropathic Post-Amputation Pain

Study Overview
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Brief Summary
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The purpose of this study is to determine if pain can be relieved by delivering small amounts of electricity (called electrical stimulation) to the nerves in an individual's amputated leg.This study will involve the use of a Peripheral Nerve Stimulation (PNS) System that is made by SPR Therapeutics (the sponsor of the study). The PNS System was cleared by the FDA for up to 60 days of use for the management of chronic pain, including extremity (leg) pain.

Official Title
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The SNAP Trial: SPRINT® Peripheral Nerve Stimulation for the Treatment of Neuropathic Post-Amputation Pain in a Randomized, Double-blinded, Placebo-controlled, Multicenter Trial

Conditions
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Neuropathic Pain, Amputation

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 21 years old Lower extremity amputation Experiencing residual limb (stump) and/or phantom limb pain Healed amputation and healthy residual limb based upon the investigator's evaluation Key Exclusion Criteria: Conditions with increased risk of infection (e.g., compromised immune system or history of recurrent skin infections) Implanted electronic device Pregnancy

Ages Eligible for Study
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Minimum Age: 21 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 |
| --- | --- |
| Active Comparator: Group 1 (Treatment)<br>Subjects in Group 1 will have Leads 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 delivers mild electrical stimulation to nerves in the residual limb. The SPRINT System includes two small wires (called Leads) that are 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: SPRINT System;|
| Sham Comparator: Group 2 (Control)<br>Subjects in Group 2 will have Leads placed in the residual limb in the upper leg. These subjects will then use the SPRINT Peripheral Nerve Stimulation (PNS) System and receive 8 weeks of sham stimulation. Subjects will then have the option to crossover and receive stimulation therapy. | Device: SPRINT Peripheral Nerve Stimulation (PNS) System<br>* The SPRINT System delivers mild electrical stimulation to nerves in the residual limb. The SPRINT System includes two small wires (called Leads) that are 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: SPRINT System;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With ≥50% Reduction in Average Post-Amputation Pain (Residual Limb Pain [RLP] and/or Phantom Limb Pain [PLP]) | All subjects were asked to complete daily diaries to record their average residual limb pain and/or phantom pain intensities during the past 24 hours on each day of a 7-day period using an 11-point numerical rating scale where 0 represents No Pain and 10 represents Pain as bad as you can imagine. The average pain scores were calculated across the 7-day period for each region of pain at baseline and across weeks 5 to 8 post-start of treatment. Percent reduction was then calculated for each subject's qualifying region of pain (residual limb and/or phantom limb pain with qualifying average pain intensity at baseline). To be considered a success, subjects must have experienced ≥ 50% reduction in all qualifying regions of pain compared to their 7-day baseline diary average pain score(s). The number of successes is presented. | Baseline and 5 to 8 weeks post-start of treatment (SOT) | 
| Number of Subjects That Experienced at Least One Study-Related Adverse Event | At each study visit following the baseline assessment at Visit 1, subjects were questioned if any changes in their medical status or condition have occurred since their previous visit. If the subject experienced a change that was a study-related 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. | Up to 14 months for each Group 1 subject and up to 18 months for each Group 2 subject (time from baseline to last study visit) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Interference | Question 9 of the Brief Pain Inventory-Short Form (BPI-9) is a 7-part question that assesses the level of interference that subjects experience in their daily lives due to pain. The 7 categories are general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. Subjects were asked to rate how much their post-amputation residual and/or phantom limb pains interfere with each aspect on an 11-point numerical scale where 0 represents Does Not Interfere and 10 represents Completely Interferes. The average of these 7 scores was calculated for each subject at each time point. Percent reduction was then calculated for each subject's qualifying region of pain (residual limb and/or phantom limb pain with qualifying average pain intensity at baseline). To be considered a success, subjects must have experienced ≥ 50% reduction in all qualifying regions of pain compared to baseline. The number of successes is presented. | Visit 1 (Baseline), Visit 7 (4-weeks post-start of treatment [SOT]), Visit 11 (8-weeks post-SOT), Visit 13 (3-months post-SOT), Visit 14 (6-months post-SOT), and Visit 16 (12-months post-SOT) | 
| Pain Disability Index (PDI) | The Pain Disability Index (PDI) is a validated survey measuring the degree to which 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 ranging from 0 to 70. A score of 0 indicates no disability while a score of 70 signifies that all of the activities in which the individual would normally be involved have been totally disrupted or prevented by pain. To be considered a success, subjects must have a ≥ 10-point reduction in their total PDI score at each time point compared to their baseline score. The number of subjects successful at each time point is reported. | Visit 1 (Baseline), Visit 7 (4-weeks post-start of treatment [SOT]), Visit 11 (8-weeks post-SOT), Visit 13 (3-months post-SOT), Visit 14 (6-months post-SOT), and Visit 16 (12-months post-SOT) | 
| Patient Global Impression of Change (PGIC) Survey | The Patient Global Impression of Change (PGIC) Survey asks subjects to rate their improvement with treatment on a 7-point scale ranging from -3 to 0 to +3, where -3 represents very much worse, 0 is no change, and +3 represents very much improved as compared to before stimulation treatment. The subjects combine all the components of their experience into one overall score. The mean rank score of each group was calculated for each time frame. | Visit 7 (4-weeks post-Start of Therapy [SOT]), Visit 11 (8-weeks post-SOT), Visit 13 (3-months post-SOT), Visit 14 (6-months post-SOT), and Visit 16 (12-months post-SOT) | 
| Pain Catastrophizing Scale (PCS) | The Pain Catastrophizing Scale (PCS) questionnaire has 13 questions that assess rumination, magnification, and helplessness. Subjects are asked to think back on painful experiences in the past and reflect on how often they had specific thoughts or feelings. Each of the 13 questions is scored on a 5-point scale where 0 represents not at all, and 4 represents all the time. The scores from each question were summed for each subject to provide a total PCS score, with a possible range from 0 to 52 with higher scores indicating a greater tendency to catastrophize pain (i.e. a higher score indicates a worse outcome). The mean score for each time point is presented. | Visit 1 (Baseline), Visit 7 (4-weeks post-Start of Treatment [SOT]), and Visit 11 (8-weeks post-SOT) | 
| Pain Medication Usage | Subjects completed 7-day diaries in which they tracked their daily use of analgesic medications. Opioid analgesic usage was converted into a morphine equivalent dosage (MED), which is measured in units of morphine milligram equivalents (MME), for subjects who were using opioid analgesics at baseline. The average MED was calculated for each subject at each time point. | Baseline, 1 to 4 weeks post-start of treatment (SOT), 5 to 8 weeks post-SOT, 3 months post-SOT, 6 months post-SOT, and 12 months post-SOT | 
| Number of Subjects With ≥ 50% Reduction in Average Post-Amputation Pain (Residual Limb Pain [RLP] and/or Phantom Limb Pain [PLP]) 1 to 4 Weeks After Start of Treatment | All subjects were asked to complete daily diaries to record their average residual limb pain and/or phantom pain intensities during the past 24 hours on each day of a 7-day period using an 11-point numerical rating scale where 0 represents No Pain and 10 represents Pain as bad as you can imagine. The average pain scores were calculated across the 7-day period for each region of pain at baseline and across weeks 1 to 4 post-start of treatment (i.e., the first half of the 8-week treatment period). Percent reduction was then calculated for each subject's qualifying region of pain (residual limb and/or phantom limb pain with qualifying average pain intensity at baseline). To be considered a success, subjects must have experienced ≥ 50% reduction in all qualifying regions of pain compared to their 7-day baseline diary average pain score(s). The number of successes is presented. | Baseline and 1 to 4 weeks post-start of treatment (SOT) | 
| Number of Subjects With ≥ 50% Reduction in Average Residual Limb Pain (RLP) 5 to 8 Weeks After Start of Treatment | All subjects were asked to complete daily diaries to record their average residual limb pain and/or phantom pain intensities during the past 24 hours on each day of a 7-day period using an 11-point numerical rating scale where 0 represents No Pain and 10 represents Pain as bad as you can imagine. The average residual limb pain scores were calculated across the 7-day period at baseline and for weeks 5 to 8 post-start of treatment (for subjects with qualifying residual limb average pain intensity at baseline). Percent reduction from baseline was then calculated, and the number of subjects that experienced ≥ 50% reduction in residual limb pain are reported. | Baseline and 5 to 8 weeks post-start of treatment (SOT) | 
| Number of Subjects With ≥ 50% Reduction in Average Phantom Limb Pain (PLP) 5 to 8 Weeks After Start of Treatment | All subjects were asked to complete daily diaries to record their average residual limb pain and/or phantom pain intensities during the past 24 hours on each day of a 7-day period using an 11-point numerical rating scale where 0 represents No Pain and 10 represents Pain as bad as you can imagine. The average phantom limb pain scores were calculated across the 7-day period at baseline and for weeks 5 to 8 post-start of treatment (for subjects with qualifying phantom limb average pain intensity at baseline). Percent reduction from baseline was then calculated, and the number of subjects that experienced ≥ 50% reduction in phantom limb pain are reported. | Baseline and 5 to 8 weeks post-start of treatment (SOT) | 
| Durability of Treatment Effect on Average Post-Amputation Pain Intensity (Residual Limb Pain [RLP] and/or Phantom Limb Pain [PLP]) | All subjects were asked to complete daily diaries to record their average residual limb pain and/or phantom limb pain intensities during the past 24 hours on each day of a 7-day period using an 11-point numerical rating scale where 0 represents No Pain and 10 represents Pain as bad as you can imagine. The average pain scores were calculated across the 7-day period for each region of pain at baseline and at 3, 6, and 12 months post-start of treatment. Percent reduction was then calculated for each subject's qualifying region of pain (residual limb and/or phantom limb pain with qualifying average pain intensity at baseline) at each time point. To be considered a success, subjects must have experienced ≥ 50% reduction in all qualifying regions of pain compared to their 7-day baseline diary average pain score(s). The number of successes is presented. | Baseline, 3-months post-Start of Treatment (SOT), 6-months post-SOT, and 12-months post-SOT |