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

NCT07285486 | Completed

• 1 other identifier: HUM00120915
• Study Type: observational
• Target: 132
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Amputation Neuroma

Outcome Measures

Primary Outcomes (6)

• Orthotics and Prosthetics Users Survey (OPUS)

  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).

  Up to 12 months postoperatively

• Pain Cognition Scale (PCS)

  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.

  Up to 12 months postoperatively

• Short-form McGill Pain Questionnaire 2 (SF-MPQ-2)

  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).

  Up to 12 months postoperatively

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

  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.

  Up to 12 months postoperatively

• PROMIS - Neuropathic Pain Quality

  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.

  Up to 12 months postoperatively

• PROMIS Pain Intensity

  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.

  Up to 12 months postoperatively

Secondary Outcomes (3)

• Patient Health Questionnaire-9 (PHQ-9) - Depression

  Up to 12 months postoperatively

• General Anxiety Disorder-7 (GAD-7) - anxiety

  Up to 12 months postoperatively

• Fibromyalgia Survey Questionnaire (FSQ)

  Up to 12 months postoperatively

Study Arms (2)

Chronic Amputation Pain

Participants who were existing amputees who had chronic neuroma pain at the amputation site.

Procedure: Amputation with Regenerative Peripheral Nerve Interfaces (RPNI)

Prophylactic Treatment Group

Participants who had a lower extremity amputated during the study and were prophylactically treated for pain.

Procedure: Amputation with Regenerative Peripheral Nerve Interfaces (RPNI); Other: Amputation Without RPNI

Interventions

Amputation Without RPNI OTHER

Standard of care for lower-extremity amputation

Prophylactic Treatment Group

Amputation with Regenerative Peripheral Nerve Interfaces (RPNI) PROCEDURE

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

Also known as: RPNI

Chronic Amputation Pain; Prophylactic Treatment Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Participants were recruited from plastic surgery, orthopedic surgery, and vascular surgery clinics.

You may qualify if:

• 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)

You may not qualify if:

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

Sponsors & Collaborators

• University of Michigan: lead

Study Sites (2)

Department of Veterans Affairs Ann Arbor Health System

Ann Arbor, Michigan, 48105, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Related Publications (1)

• Lee JC, Kubiak CA, Best CSW, Hamill JB, Ki J, Kim HM, Roth RS, Kozlow JH, Tinney MJ, Geisser ME, Cederna PS, Kemp SWP, Kung TA. Regenerative Peripheral Nerve Interface Surgery to Treat Chronic Postamputation Pain: A Prospective Study in Major Lower Limb Amputation Patients. Ann Surg Open. 2025 Jan 7;6(1):e535. doi: 10.1097/AS9.0000000000000535. eCollection 2025 Mar.

  PMID: 40134500 RESULT

MeSH Terms

Interventions

Amputation, Surgical

Intervention Hierarchy (Ancestors)

Orthopedic Procedures; Surgical Procedures, Operative

Study Officials

• Theodore Kung, MD

  University of Michigan

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investogator

Study Record Dates

• First Submitted: December 2, 2025
• First Posted: December 16, 2025
• Study Start: June 8, 2017
• Primary Completion: June 26, 2023
• Study Completion: June 26, 2023
• Last Updated: December 16, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)