Amputation NeuromaNCT07285486
Regenerative Peripheral Nerve Interfaces for the Treatment of Painful Neuromas in Major Limb Amputees
An observational study of Amputation Neuroma, run by University of Michigan at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Amputation Neuroma
- What is being tested?
- Amputation with Regenerative Peripheral Nerve Interfaces (RPNI) and Amputation Without RPNI
- Type of treatment
- Surgery or procedure
- How many people
- 132 participants
- Where
- 2 sitesUnited States
- Study dates
- 8 Jun 2017to 26 Jun 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Participants were recruited from plastic surgery, orthopedic surgery, and vascular surgery clinics.
Who may be able to join
- 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)
Who cannot join
- History of chronic amputation-related pain (prophylactic pain treatment group only)
- History of regenerative peripheral nerve interface (RPNI)
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Department of Veterans Affairs Ann Arbor Health System
Ann Arbor, Michigan, 48105
University of Michigan
Ann Arbor, Michigan, 48109
About this study
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
- Being tested
- Amputation with Regenerative Peripheral Nerve Interfaces (RPNI), Amputation Without RPNI
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Amputation with Regenerative Peripheral Nerve Interfaces (RPNI)Procedure or surgery
Also called RPNI
Free-muscle graft over cut nerve ends for treatment of neuromas at site of an amputation.
Amputation Without RPNIOther
Standard of care for lower-extremity amputation
| Study group | Role | What they receive |
|---|---|---|
| Chronic Amputation Pain | Participants who were existing amputees who had chronic neuroma pain at the amputation site. Receives: 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. Receives: Procedure: Amputation with Regenerative Peripheral Nerve Interfaces (RPNI); Other: Amputation Without RPNI |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to 12 months postoperatively
Secondary outcomes (3)
Patient Health Questionnaire-9 (PHQ-9) - Depression
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.
Measured: Up to 12 months postoperatively
General Anxiety Disorder-7 (GAD-7) - anxiety
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).
Measured: Up to 12 months postoperatively
Fibromyalgia Survey Questionnaire (FSQ)
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.
Measured: Up to 12 months postoperatively
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Dec 2025
- Study start8 Jun 2017
- Primary completion26 Jun 2023
- Study completion26 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Amputation NeuromaStudies of the same condition, open and under way.
- More trials run by University of MichiganThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 132 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Theodore Alexander Kung, University of Michigan
- Investigators
- Theodore Kung, MD, Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07285486
- Sponsor's protocol ID
- HUM00120915
- Status last verified
- Dec 2025
- First submitted
- 2 Dec 2025
- Last updated
- 16 Dec 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 40134500
Study at a glance
From the registry record, last updated by the sponsor on 16 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Regenerative Peripheral Nerve Interfaces for the Treatment of Painful Neuromas in Major Limb Amputees
- ClinicalTrials.gov ID
- NCT07285486
- Acronym / sponsor ID
- HUM00120915
- Conditions
- Amputation Neuroma
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 132 participants (actual)
- Lead sponsor
- University of MichiganUniversity, hospital or other
- Study start
- 8 Jun 2017 (actual)
- Primary completion
- 26 Jun 2023 (actual)
- Study completion
- 26 Jun 2023 (actual)
- First posted
- 16 Dec 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Chronic Amputation Pain | – | Procedure: Amputation with Regenerative Peripheral Nerve Interfaces (RPNI)Participants who were existing amputees who had chronic neuroma pain at the amputation site. |
| Prophylactic Treatment Group | – | Procedure: Amputation with Regenerative Peripheral Nerve Interfaces (RPNI), Other: Amputation Without RPNIParticipants who had a lower extremity amputated during the study and were prophylactically treated for pain. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Participants were recruited from plastic surgery, orthopedic surgery, and vascular surgery clinics.
Key inclusion criteria (3 listed)
- 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)
Key exclusion criteria (2 listed)
- History of chronic amputation-related pain (prophylactic pain treatment group only)
- History of regenerative peripheral nerve interface (RPNI)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Amputation with Regenerative Peripheral Nerve Interfaces (RPNI)Also: RPNIFree-muscle graft over cut nerve ends for treatment of neuromas at site of an amputation. | Procedure or surgery | Chronic Amputation Pain, Prophylactic Treatment Group |
| Amputation Without RPNIStandard of care for lower-extremity amputation | Other | Prophylactic Treatment Group |
Primary outcome
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).
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.
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).
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.
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.
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.
3 secondary outcomes
Patient Health Questionnaire-9 (PHQ-9) - Depression
Time frame: Up to 12 months postoperatively
General Anxiety Disorder-7 (GAD-7) - anxiety
Time frame: Up to 12 months postoperatively
Fibromyalgia Survey Questionnaire (FSQ)
Time frame: Up to 12 months postoperatively
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Dec 2025.
- Results publication: PubMed 40134500Lee 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Theodore Kung, MD principal investigator
University of Michigan
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Amputation Neuroma, run by University of Michigan at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Orthotics and Prosthetics Users Survey (OPUS) (time frame: Up to 12 months postoperatively). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07285486, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Dec 2025.