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NCT Number: NCT07285486

Regenerative Peripheral Nerve Interfaces for the Treatment of Painful Neuromas in Major Limb Amputees

The Regenerative Peripheral Nerve Interface (RPNI) is a novel strategy to prevent neuroma formation in transected peripheral nerves. The RPNI consists of a residual peripheral nerve that is implanted into a free skeletal muscle graft either at the time of limb amputation or after excision of a terminal neuroma bulb. The sprouting axons of the nerve readily reinnervate the free muscle graft, thereby greatly reducing the chance of neuroma formation.

This investigation has a prospective cohort study design involving major lower limb amputees drawn from both the University of Michigan Health Systems and VA Health System of Ann Arbor. To objectively evaluate the effect of RPNI surgery on patients' perception of pain and to measure other health-related quality of life metrics relating to neuroma pain, this clinical trial will utilize specific, validated patient-reported outcomes measures (PROMs) to assess targeted domains in patients with major limb amputation. These survey instruments will determine: 1) patterns of pain medication use, including the use of opioids, 2) functional status and use of a prosthetic device, 3) changes in neuroma pain quality, 4) limitations in activities of daily living due to neuroma pain, 5) depression and anxiety relating to neuroma pain.

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Key information

Conditions

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Department of Veterans Affairs Ann Arbor Health System, Ann Arbor, Michigan, United States

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Major lower limb amputation (chronic pain treatment group only)
  • Symptomatic residual limb neuroma (chronic pain treatment group only)
  • Undergoing a major lower limb amputation (prophylactic pain treatment group only)

Exclusion criteria

  • History of chronic amputation-related pain (prophylactic pain treatment group only)
  • History of regenerative peripheral nerve interface (RPNI)

Treatment and study plan

Amputation with Regenerative Peripheral Nerve Interfaces (RPNI)

Procedure

Free-muscle graft over cut nerve ends for treatment of neuromas at site of an amputation.

Other names: RPNI

Amputation Without RPNI

Other

Standard of care for lower-extremity amputation

Primary outcomes

  1. Orthotics and Prosthetics Users Survey (OPUS)

    Time frame: Up to 12 months postoperatively

    The OPUS was a self-report questionnaire consisting of five modules. It can be used for prosthetic and orthotic programs for quality assessment, to maintain awareness of improvement in activities, to evaluate changes in patient's functional status and quality of life, and to assess satisfaction with devices and services. This study used the Functional Status Measure module, which was a 20-question survey that used a Likert scale ranging from 1 (very easy) to 5 (cannot do this activity).

  2. Pain Cognition Scale (PCS)

    Time frame: Up to 12 months postoperatively

    The PCS evaluated the relationship between thoughts and pain. The PCS was a 13-question survey that used a Likert scale ranging from 0 (not at all) to 4 (all the time). Total score ranged from 0 (no pain catastrophizing) to 52 (highest level of pain catastrophizing), with a score of 30 indicating a clinically high level of pain catastrophizing.

  3. Short-form McGill Pain Questionnaire 2 (SF-MPQ-2)

    Time frame: Up to 12 months postoperatively

    The SF-MPQ-2 was a pain assessment tool that measured both neuropathic and non-neuropathic pain. It used 22 descriptors, grouped into four subscales (continuous, intermittent, neuropathic, and affective) along with a Present Pain Intensity (PPI) scale. The descriptors and PPI all used a Likert scale that ranged from 0 (none) to 10 (worst possible). The SF-MPQ-2 was scored by calculating the average ratings for each of the four subscales and the total pain score and averaging all 22 item ratings, resulting in a score ranging from 0 (none) to 10 (worst possible).

  4. Patient-Reported Outcomes Measurement Information System (PROMIS) - Pain Interference

    Time frame: Up to 12 months postoperatively

    The PROMIS was a system of standardized, scientifically validated questions used to measure a patient's physical, mental, and social health status. The PROMIS pain interference short form had 6 questions ranging from 1 [not at all] to 5 [very much]. The PROMIS was scored by summing the values of the responses within each short form. The raw score was converted to a standardized T-score using specific scoring tables found in the instrument's scoring manual.

  5. PROMIS - Neuropathic Pain Quality

    Time frame: Up to 12 months postoperatively

    The PROMIS was a system of standardized, scientifically validated questions used to measure a patient's physical, mental, and social health status. The PROMIS neuropathic pain quality short form had 5 questions ranging from 1 [not at all] to 5 [very much]. The PROMIS was scored by summing the values of the responses within each short form. The raw score was converted to a standardized T-score using specific scoring tables found in the instrument's scoring manual.

  6. PROMIS Pain Intensity

    Time frame: Up to 12 months postoperatively

    The PROMIS was a system of standardized, scientifically validated questions used to measure a patient's physical, mental, and social health status. The PROMIS pain intensity short form had 3 questions ranging from 0 [had no pain] to 5 [very severe]. The PROMIS was scored by summing the values of the responses within each short form. The raw score was converted to a standardized T-score using specific scoring tables found in the instrument's scoring manual.

Secondary outcomes

  1. Patient Health Questionnaire-9 (PHQ-9) - Depression

    Time frame: Up to 12 months postoperatively

    The PHQ-9 was a nine-question self-report questionnaire used to screen for depression, diagnose its severity, and monitor treatment response. Each of the nine questions was scored on a four-point scale from 0 ("Not at all") to 3 ("Nearly every day"). The PHQ-9 asked about the frequency of specific depressive symptoms over the past two weeks, with a total score ranging from 0 to 27, with scores below 5 indicating no depression and scores above 20 indicating severe depression.

  2. General Anxiety Disorder-7 (GAD-7) - anxiety

    Time frame: Up to 12 months postoperatively

    The GAD-7 was a seven-item questionnaire used to screen for and measure the severity of generalized anxiety disorder (GAD). It asked about symptoms like feeling nervous, worrying too much, and trouble relaxing, with responses scored from 0 to 3 for each of the seven questions. The total score, ranging from 0 to 21, is interpreted to indicate the level of anxiety: 0-4 (minimal), 5-9 (mild), 10-14 (moderate), and 15-21 (severe).

  3. Fibromyalgia Survey Questionnaire (FSQ)

    Time frame: Up to 12 months postoperatively

    The FSQ was a tool used to assess the key symptoms of fibromyalgia by evaluating widespread pain and the severity of other somatic symptoms. It was comprised of two tools, the widespread pain index (WPI) subsection and the symptom severity score (SSS), which were summed to get a result. The WPI asked participants to mark off from a list of 19 potential pain locations on a body diagram. which were summed. The total score ranged from 0 to 19. The SSS evaluated the severity of three major symptoms and the severity of other somatic symptoms. The SSS consisted of 6 questions with a total score ranging from 0 to 12. The total range of both tools combined was 0 to 31, with a total score of ≥13 supporting a diagnosis of fibromyalgia.

Sponsors and collaborators

Lead sponsor

University of Michigan

Other

Registry information

Important dates

Study start
2017
Primary completion
2023
Study completion
2023
First posted
Dec 16, 2025
Registry last updated
Dec 16, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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