Amputation NeuromaTreatPAPNCT07605754
Results of Nerve Surgery to Treat PostAmputation Pain
An observational study of Amputation Neuroma, run by Leiden University Medical Center at 1 site in Netherlands.
Trial summary
Rationale: Postamputation pain (PAP) is frequently seen after amputations and is a severe lifelong disabling condition affecting quality of life (QoL). Different nerve surgical techniques are available to treat PAP if non-surgical treatment options are not sufficient. 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?
- Fascicular split and Targeted Muscle Reinnervation
- Type of treatment
- Surgery or procedure
- How many people
- 98 participants
- Where
- 1 siteNetherlands
- Study dates
- 14 Aug 2025to 20 Aug 2029
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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: Patients with intractable postamputation pain after a major extremity amputation (trans humeral, elbow disarticulation, forearm, transfemoral, knee disarticulation, and transtibial) undergoing surgical postamputation pain treatment in our center.
Who may be able to join
- Age older than or equal to 18 years
- Intractable postamputation pain
Who cannot join
- Cognitive impairment or delirium at the time of inclusion
- Having received previous radiotherapy on the affected limb
- Patients who are unable to comprehend the informed consent form or the questionnaires used in the current study
- Unfit for general anesthesia
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands1 site, 1 recruiting
- Recruiting
Leiden University Medical Center
Leiden, South Holland, 2333 ZA
About this study
Official title: Results of Nerve Surgery to Treat PostAmputation Pain (TreatPAP): a Prospective Study
Rationale: Postamputation pain (PAP) is frequently seen after amputations and is a severe lifelong disabling condition affecting quality of life (QoL). Different nerve surgical techniques are available to treat PAP if non-surgical treatment options are not sufficient. Multiple techniques have been described for treatment of symptomatic neuromas with varying results. Techniques described include traction neurectomy with/without implantation, nerve grafting, nerve capping, regenerative peripheral nerve interface, and targeted muscle reinnervation (TMR). In the Leiden University Medical Center (LUMC), the most common techniques to treat painful neuromas include TMR and fascicular split (FS). TMR involves coaptating the transected mixed nerve to functional motor nerves, showing promising results in recent studies. FS is a technique closely related to neurectomy with implantation in a functional muscle. The difference is that with FS, the nerve is split into fascicles before implantation to allow for better distribution of nerve fibers. These techniques have not yet been compared. In this study, the investigators will compare both these techniques in a prospective setting for the treatment of PAP. The hypothesis is, that after 12 months, pain will be diminished and QoL will be increased in all patients versus the pre-operative status. There will be little to no difference in outcome between the surgical techniques used.
Objective: To evaluate limb pain in patients with intractable postamputation pain (residual limb pain and phantom limb pain) one year after nerve embedding surgery following the standardized workup of the LUMC.
Read more
Study design: Prospective study Study population: Patients 18 years of age or older, with a history of more than 6 months of intractable postamputation neuropathic limb pain, with no history of previous surgical intervention for pain treatment, referred to the Leiden Nerve Center.
Main study parameters/endpoints: The mean difference in pain scores for phantom limb pain and residual limb pain one year postoperatively. An average pain score from the past 7 days is used for PLP and RLP individually, on the 11-point (0-10) numerical rating scale (NRS). Additionally, the Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Behavior and Interference Questionnaire Short Forms (7a and 8a, respectively) are used one year postoperatively.
Nature and extent of the burden and risks associated with participation, benefit, and group relatedness: Both techniques are currently used in the Leiden University Medical Center (LUMC) and considered standard of care. The decision to perform either technique is solely dependent on the personal preference of the treating nerve surgeon. The results of this trial will improve the understanding of the treatment effect of both surgical techniques with a minimal patient burden. Participation requires patients to complete 3-4 non-invasive questionnaires about pain, quality of life, depression and anxiety, and mobility over a period of 2 years. The pre-operative (if applicable) and 12-month postoperative questionnaire will each take approximately 15 minutes to complete. The other two questionnaires at 18 and 24 months postoperative will take approximately 3-4 minutes to complete. Additionally, participants will fill out a daily questionnaire consisting of one to three questions about pain for 7 consecutive days at 12 months.
Read the detailed description
Postamputation pain (PAP) is a common sequela after major lower limb amputation, with an estimated incidence of 61%. PAP can be divided into two major categories: phantom limb pain (PLP) and residual limb pain (RLP, 'stump pain'). Both RLP and PLP are predominantly driven by the cut nerve endings during the amputation, that form terminal-neuromas. PAP is known to compromise prosthetic rehabilitation and profoundly diminishes the quality of life after amputation. When PAP develops, it is extremely difficult to treat. When non-surgical treatment fails, or side effects of medication dominate patients' lives, surgery for PAP is occasionally undertaken. Nerve surgical techniques that are then applied differ widely and lack any solid scientific base. In general, secondary surgery for PAP includes resection of the neuroma and transposition of the freshened nerve into a more favorable environment, such as muscle, bone, vessels, or fat. This nerve implantation technique has been described since 1918 to treat painful neuromas, showing good results ranging from 64 to 82% of pain relief. Based on the vast experience gained over a 25-year period in the Leiden Nerve Center in treating painful neuromas, an adaptation of the nerve implantation method was developed called the Fascicular Split (FS) technique to treat PAP. In the FS technique, after transecting the neuroma, the nerve is first split into multiple fascicles before implanting the nerve in the muscle. This allows for better distribution of the nerve in the muscle, resulting in less neuroma formation. The strength of FS is its relative simplicity, which is crucial for the wider implementation in routine care. Promising results were observed applying this technique in a small series (n=8) of patients with PAP yielding a long-lasting, life-changing effect in all but one patient. In some cases, FS was performed years after the initial amputation and after previous failed neuroma surgeries. Other nerve handling techniques to treat symptomatic neuroma include centro-central neurorrhaphy, End-to-Side neurorrhaphy, Graft to Nowhere, Targeted Muscle Reinnervation (TMR), and Regenerative Peripheral Nerve Interface. TMR is, after simply embedding the nerve in healthy tissue, the best studied and most promising technique to treat PAP. Several cohort studies and a recent randomized trial in secondary surgery for PAP show that a nerve surgical technique called Targeted Muscle Reinnervation (TMR) is effective in treating PAP. However, the main disadvantage of TMR is that it is a time-consuming procedure.
To date, there are no studies that compare both techniques for the treatment of PAP. The investigators believe that the treatment FS yields similar results to TMR. Moreover, in terms of clinical applicability, the FS technique is easier to learn, does not require extensive nerve surgical skills, and does not take much time to perform.
Few papers have been published on TMR as a treatment for postamputation pain. Despite issues with the validity of the articles, results of PLP and RLP were consistently in favor of TMR as a technique regarding all outcome measures, including intensity and interference with daily activities. FS, although not mentioned in the literature, has many similarities with nerve implantation, which showed similarly good results for the treatment of painful neuromas. However, there have been no studies to date that directly compare the two techniques.
PAP is a lifelong disabling condition profoundly affecting quality of life. Nerve embedding surgical techniques (simple, FS, and TMR) have proven to be effective to treat postamputation pain. Preliminary results show that simple embedding, TMR, and FS are potentially good techniques to treat invalidating PAP. However, no comparative studies have been performed.
The investigators hypothesize that FS will show equally good results compared to TMR in the surgical treatment of intractable PAP, reducing pain, and improving quality-of-life (QoL) and mobility.
The investigators propose a prospective observational cohort study evaluating outcomes after various nerve embedding techniques following a standardized selection protocol in patients with intractable post-amputation pain after a major limb amputation.
- Conditions
- Amputation Neuroma
- Being tested
- Fascicular split, Targeted Muscle Reinnervation
- Keywords
- Neuroma, Amputation, pain, Targeted Muscle Reinnervation, Nerve embedding
- Medical subject headings
- Neuroma, Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fascicular splitProcedure or surgery
Also called nerve embedding
Fasicular split surgical technique:
- Painful nerve is identified and the neuroma is resected.
- Split the nerve into its constituent multiple nerve fascicles
- Create a deep muscle pocket for each individual fascicle
- Plant each fascicle into a separate muscle compartment and fixate the fascicle in place with tissue glue.
Targeted Muscle ReinnervationProcedure or surgery
Targeted Muscle Reinnervation surgical technique
- Painful nerve is identified and the neuroma is resected.
- A nerve stimulator is used to identify functional motor nerve branches. Near the point where the motor branch enters the muscle, the motor nerve branch is transected
- End-to-end nerve coaptation is performed between the amputated nerve and the transected motor nerve branch.
| Study group | Role | What they receive |
|---|---|---|
| Control: Targeted Muscle Reinnervation (TMR) | Patients with a symptomatic neuroma requiring surgical intervention Receives: Procedure: Targeted Muscle Reinnervation | |
| Intervention: Fascicular split | Patients with a symptomatic neuroma requiring surgical intervention Receives: Procedure: Fascicular split |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phantom limb pain measured on the 11-point (0-10) numeric rating scale.
A primary endpoint is the mean phantom limb pain experience one year postoperatively. This will be measured on the 11-point (0-10) numeric rating scale over 7 consecutive days. A higher score indicates worse pain.
Measured: 1 year postoperatively
Residual limb pain measured on the 11-point numeric rating scale
A primary endpoint is the mean residual limb pain experience one year postoperatively. This will be measured on the 11-point (0-10) numeric rating scale over 7 consecutive days. A higher score indicates worse pain.
Measured: 1 year postoperatively
PROMIS pain behavior short form 7a
PROMIS pain behavior short form 7a in Dutch-Flemish
Measured: 1 year postoperatively
PROMIS pain interference short form 8a
PROMIS pain interference short form 8a in Dutch-Flemish
Measured: 1 year postoperatively
Secondary outcomes (16)
Phantom limb pain using the 11-point (0-10) numeric rating scale
Measured: From enrolment until 24 months post-operatively
Residual limb pain using the 11-point (0-10) numeric rating scale
Measured: From enrolment until 24 months postoperatively
PROMIS pain behavior 7a short form in Dutch-Flemish
Measured: From enrolment until 24 months postoperatively
PROMIS pain interference 8a short form in Dutch-Flemish
Measured: From enrolment until 24 months postoperatively
Quality of life (EQ-5D-5L)
Measured: From enrolment until 24 months postoperatively
Pain type using the ICAN localization map
Measured: From enrolment until 12 months postoperatively
Neuropathic pain using the PainDetect
Measured: From enrolment until 12 months postoperatively
Hospital anxiety and depression using the HADS
Measured: From enrolment until 12 months postoperatively
Perceived treatment effect using the GPE-DV
Measured: at 12 months postoperativley
Prosthetic rehabilitation using the PLUS-M
Measured: From enrolment until 12 months postoperatively
Changes in sensory quality in the amputated stump using quantitative sensory testing (QST)
Measured: at enrolment until 12 months postoperative
Quantified neuroma perfusion using near-infrared fluorescence using indocyanine green
Patients will receive near-infrared (NIR) fluorescence imaging with indocyanine green (ICG) during the surgery. ICG is a fluorescent dye that binds to plasma proteins and emits light when excited by near-infrared wavelengths. After intravenous injection, the dye circulates rapidly, allowing surgeons to assess blood flow to tissue of interest. This method has very good safety profile and has been used extensively in gastro-intestinal, reconstructive, vascular and neurosurgery. This study aims to use quantified ICG NIR fluorescence imaging to evaluate perfusion patterns of symptomatic and asymptomatic neuromas after amputation.
Measured: Peri-operatively
Surgery duration
in minutes
Measured: Perioperatively
Length of hospital stay
Amount of days patients spent in hospital post surgery
Measured: From the date of surgery to the date of discharge from the hospital, up to 1 year post surgery
Adverse events
i.e., infection, rebleed, with Clavien-Dindo scores
Measured: until 30 days postoperatively
Medication Quantification Scale
Phantom limb pain, residual limb pain, the PROMIS pain behavior 7a short form, and the PROMIS interference 8a short form will be corrected for pain medication use, using the medication quantification scale. A higher score indicates more pain medication use.
Measured: until 24 months postoperatively
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 May 2026
- Study start14 Aug 2025
- Primary completion20 Aug 2028 (estimated)
- Study completion20 Aug 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (20)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 Leiden University Medical CenterThe 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
- Case-control
- Time perspective
- Prospective
- Enrolment
- 98 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Leiden University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, jlgroen, Leiden University Medical Center
- Investigators
- Justus L. Groen, MD, PhD, Principal investigator, Leiden University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07605754
- Sponsor's protocol ID
- 25-3058
- Acronym
- TreatPAP
- Status last verified
- May 2026
- First submitted
- 15 Sep 2025
- Last updated
- 26 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Undecided
Publications
Anné C, de Laat FA, Hafner BJ, et al. "Dutch-Flemish translation of the Prosthetic Limb Users Survey of Mobility (PLUS-M)". Poster tijdens het PROMIS congres Praag. 2022.
Hudak PL, Wright JG. The characteristics of patient satisfaction measures. Spine (Phila Pa 1976). 2000 Dec 15;25(24):3167-77. doi: 10.1097/00007632-200012150-00012.
PubMed 11124733Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983 Jun;67(6):361-70. doi: 10.1111/j.1600-0447.1983.tb09716.x.
PubMed 6880820Freynhagen R, Baron R, Gockel U, Tolle TR. painDETECT: a new screening questionnaire to identify neuropathic components in patients with back pain. Curr Med Res Opin. 2006 Oct;22(10):1911-20. doi: 10.1185/030079906X132488.
PubMed 17022849Gomez-Eslava B, Raasveld FV, Hoftiezer YAJ, McCarty JC, Daddario JL, Valerio IL, Heng M, Eberlin KR. Pain Sketches to Predict Pain following Primary Targeted Muscle Reinnervation in Amputees. Plast Reconstr Surg. 2024 May 1;153(5):1162-1171. doi: 10.1097/PRS.0000000000010762. Epub 2023 May 26.
PubMed 37252909Herdman M, Gudex C, Lloyd A, Janssen M, Kind P, Parkin D, Bonsel G, Badia X. Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L). Qual Life Res. 2011 Dec;20(10):1727-36. doi: 10.1007/s11136-011-9903-x. Epub 2011 Apr 9.
PubMed 21479777Harden RN, Weinland SR, Remble TA, Houle TT, Colio S, Steedman S, Kee WG; American Pain Society Physicians. Medication Quantification Scale Version III: update in medication classes and revised detriment weights by survey of American Pain Society Physicians. J Pain. 2005 Jun;6(6):364-71. doi: 10.1016/j.jpain.2005.01.350.
PubMed 15943958Terwee CB, Roorda LD, de Vet HC, Dekker J, Westhovens R, van Leeuwen J, Cella D, Correia H, Arnold B, Perez B, Boers M. Dutch-Flemish translation of 17 item banks from the patient-reported outcomes measurement information system (PROMIS). Qual Life Res. 2014 Aug;23(6):1733-41. doi: 10.1007/s11136-013-0611-6. Epub 2014 Jan 9.
PubMed 24402179Schafer B, Freund G, Orr J, Nolte K, Weis J, Bahm J, Beier JP. Technique and Expected Benefit of Intraoperative Perfusion Imaging of Peripheral Nerves. Plast Reconstr Surg Glob Open. 2024 Nov 5;12(11):e6281. doi: 10.1097/GOX.0000000000006281. eCollection 2024 Nov.
PubMed 39507316O'Brien AL, Jordan SW, West JM, Mioton LM, Dumanian GA, Valerio IL. Targeted Muscle Reinnervation at the Time of Upper-Extremity Amputation for the Treatment of Pain Severity and Symptoms. J Hand Surg Am. 2021 Jan;46(1):72.e1-72.e10. doi: 10.1016/j.jhsa.2020.08.014. Epub 2020 Oct 22.
PubMed 33268236Berger LE, Shin S, Haffner ZK, Huffman SS, Spoer DL, Sayyed AA, Franzoni G, Bekeny JC, Attinger CE, Kleiber GM. The application of targeted muscle reinnervation in lower extremity amputations: A systematic review. Microsurgery. 2023 Oct;43(7):736-747. doi: 10.1002/micr.31030. Epub 2023 Mar 2.
PubMed 36864779Farrar JT, Young JP Jr, LaMoreaux L, Werth JL, Poole MR. Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain. 2001 Nov;94(2):149-158. doi: 10.1016/S0304-3959(01)00349-9.
PubMed 11690728Kang NV, Woollard A, Michno DA, Al-Ajam Y, Tan J, Hansen E. A consecutive series of targeted muscle reinnervation (TMR) cases for relief of neuroma and phantom limb pain: UK perspective. J Plast Reconstr Aesthet Surg. 2022 Mar;75(3):960-969. doi: 10.1016/j.bjps.2021.09.068. Epub 2021 Oct 22.
PubMed 34840118Mioton LM, Dumanian GA, Shah N, Qiu CS, Ertl WJ, Potter BK, Souza JM, Valerio IL, Ko JH, Jordan SW. Targeted Muscle Reinnervation Improves Residual Limb Pain, Phantom Limb Pain, and Limb Function: A Prospective Study of 33 Major Limb Amputees. Clin Orthop Relat Res. 2020 Sep;478(9):2161-2167. doi: 10.1097/CORR.0000000000001323.
PubMed 32452928Dumanian GA, Potter BK, Mioton LM, Ko JH, Cheesborough JE, Souza JM, Ertl WJ, Tintle SM, Nanos GP, Valerio IL, Kuiken TA, Apkarian AV, Porter K, Jordan SW. Targeted Muscle Reinnervation Treats Neuroma and Phantom Pain in Major Limb Amputees: A Randomized Clinical Trial. Ann Surg. 2019 Aug;270(2):238-246. doi: 10.1097/SLA.0000000000003088.
PubMed 30371518
Study at a glance
From the registry record, last updated by the sponsor on 26 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Results of Nerve Surgery to Treat PostAmputation Pain (TreatPAP): a Prospective Study
- ClinicalTrials.gov ID
- NCT07605754
- Acronym / sponsor ID
- TreatPAP / 25-3058
- Conditions
- Amputation Neuroma
- Keywords
- Neuroma, Amputation, pain, Targeted Muscle Reinnervation, Nerve embedding
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 98 participants (estimated)
- Lead sponsor
- Leiden University Medical CenterUniversity, hospital or other
- Study start
- 14 Aug 2025 (actual)
- Primary completion
- 20 Aug 2028 (estimated)
- Study completion
- 20 Aug 2029 (estimated)
- First posted
- 26 May 2026 (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.
Rationale: Postamputation pain (PAP) is frequently seen after amputations and is a severe lifelong disabling condition affecting quality of life (QoL). Different nerve surgical techniques are available to treat PAP if non-surgical treatment options are not sufficient. Multiple techniques have been described for treatment of symptomatic neuromas with varying results. Techniques described include traction neurectomy with/without implantation, nerve grafting, nerve capping, regenerative peripheral nerve interface, and targeted muscle reinnervation (TMR). In the Leiden University Medical Center (LUMC), the most common techniques to treat painful neuromas include TMR and fascicular split (FS). TMR involves coaptating the transected mixed nerve to functional motor nerves, showing promising results in recent studies. FS is a technique closely related to neurectomy with implantation in a functional muscle. The difference is that with FS, the nerve is split into fascicles before implantation to allow for better distribution of nerve fibers. These techniques have not yet been compared. In this study, the investigators will compare both these techniques in a prospective setting for the treatment of PAP. The hypothesis is, that after 12 months, pain will be diminished and QoL will be increased in all patients versus the pre-operative status. There will be little to no difference in outcome between the surgical techniques used.
Objective: To evaluate limb pain in patients with intractable postamputation pain (residual limb pain and phantom limb pain) one year after nerve embedding surgery following the standardized workup of the LUMC.
Study design: Prospective study Study population: Patients 18 years of age or older, with a history of more than 6 months of intractable postamputation neuropathic limb pain, with no history of previous surgical intervention for pain treatment, referred to the Leiden Nerve Center.
Main study parameters/endpoints: The mean difference in pain scores for phantom limb pain and residual limb pain one year postoperatively. An average pain score from the past 7 days is used for PLP and RLP individually, on the 11-point (0-10) numerical rating scale (NRS). Additionally, the Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Behavior and Interference Questionnaire Short Forms (7a and 8a, respectively) are used one year postoperatively.
Nature and extent of the burden and risks associated with participation, benefit, and group relatedness: Both techniques are currently used in the Leiden University Medical Center (LUMC) and considered standard of care. The decision to perform either technique is solely dependent on the personal preference of the treating nerve surgeon. The results of this trial will improve the understanding of the treatment effect of both surgical techniques with a minimal patient burden. Participation requires patients to complete 3-4 non-invasive questionnaires about pain, quality of life, depression and anxiety, and mobility over a period of 2 years. The pre-operative (if applicable) and 12-month postoperative questionnaire will each take approximately 15 minutes to complete. The other two questionnaires at 18 and 24 months postoperative will take approximately 3-4 minutes to complete. Additionally, participants will fill out a daily questionnaire consisting of one to three questions about pain for 7 consecutive days at 12 months.
Detailed description
Postamputation pain (PAP) is a common sequela after major lower limb amputation, with an estimated incidence of 61%. PAP can be divided into two major categories: phantom limb pain (PLP) and residual limb pain (RLP, 'stump pain'). Both RLP and PLP are predominantly driven by the cut nerve endings during the amputation, that form terminal-neuromas. PAP is known to compromise prosthetic rehabilitation and profoundly diminishes the quality of life after amputation. When PAP develops, it is extremely difficult to treat. When non-surgical treatment fails, or side effects of medication dominate patients' lives, surgery for PAP is occasionally undertaken. Nerve surgical techniques that are then applied differ widely and lack any solid scientific base. In general, secondary surgery for PAP includes resection of the neuroma and transposition of the freshened nerve into a more favorable environment, such as muscle, bone, vessels, or fat. This nerve implantation technique has been described since 1918 to treat painful neuromas, showing good results ranging from 64 to 82% of pain relief. Based on the vast experience gained over a 25-year period in the Leiden Nerve Center in treating painful neuromas, an adaptation of the nerve implantation method was developed called the Fascicular Split (FS) technique to treat PAP. In the FS technique, after transecting the neuroma, the nerve is first split into multiple fascicles before implanting the nerve in the muscle. This allows for better distribution of the nerve in the muscle, resulting in less neuroma formation. The strength of FS is its relative simplicity, which is crucial for the wider implementation in routine care. Promising results were observed applying this technique in a small series (n=8) of patients with PAP yielding a long-lasting, life-changing effect in all but one patient. In some cases, FS was performed years after the initial amputation and after previous failed neuroma surgeries. Other nerve handling techniques to treat symptomatic neuroma include centro-central neurorrhaphy, End-to-Side neurorrhaphy, Graft to Nowhere, Targeted Muscle Reinnervation (TMR), and Regenerative Peripheral Nerve Interface. TMR is, after simply embedding the nerve in healthy tissue, the best studied and most promising technique to treat PAP. Several cohort studies and a recent randomized trial in secondary surgery for PAP show that a nerve surgical technique called Targeted Muscle Reinnervation (TMR) is effective in treating PAP. However, the main disadvantage of TMR is that it is a time-consuming procedure.
To date, there are no studies that compare both techniques for the treatment of PAP. The investigators believe that the treatment FS yields similar results to TMR. Moreover, in terms of clinical applicability, the FS technique is easier to learn, does not require extensive nerve surgical skills, and does not take much time to perform.
Few papers have been published on TMR as a treatment for postamputation pain. Despite issues with the validity of the articles, results of PLP and RLP were consistently in favor of TMR as a technique regarding all outcome measures, including intensity and interference with daily activities. FS, although not mentioned in the literature, has many similarities with nerve implantation, which showed similarly good results for the treatment of painful neuromas. However, there have been no studies to date that directly compare the two techniques.
PAP is a lifelong disabling condition profoundly affecting quality of life. Nerve embedding surgical techniques (simple, FS, and TMR) have proven to be effective to treat postamputation pain. Preliminary results show that simple embedding, TMR, and FS are potentially good techniques to treat invalidating PAP. However, no comparative studies have been performed.
The investigators hypothesize that FS will show equally good results compared to TMR in the surgical treatment of intractable PAP, reducing pain, and improving quality-of-life (QoL) and mobility.
The investigators propose a prospective observational cohort study evaluating outcomes after various nerve embedding techniques following a standardized selection protocol in patients with intractable post-amputation pain after a major limb amputation.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control: Targeted Muscle Reinnervation (TMR) | – | Procedure: Targeted Muscle ReinnervationPatients with a symptomatic neuroma requiring surgical intervention |
| Intervention: Fascicular split | – | Procedure: Fascicular splitPatients with a symptomatic neuroma requiring surgical intervention |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with intractable postamputation pain after a major extremity amputation (trans humeral, elbow disarticulation, forearm, transfemoral, knee disarticulation, and transtibial) undergoing surgical postamputation pain treatment in our center.
Key inclusion criteria (2 listed)
- Age older than or equal to 18 years
- Intractable postamputation pain
Key exclusion criteria (4 listed)
- Cognitive impairment or delirium at the time of inclusion
- Having received previous radiotherapy on the affected limb
- Patients who are unable to comprehend the informed consent form or the questionnaires used in the current study
- Unfit for general anesthesia
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 |
|---|---|---|
| Fascicular splitAlso: nerve embeddingFasicular split surgical technique: 1. Painful nerve is identified and the neuroma is resected. 2. Split the nerve into its constituent multiple nerve fascicles 3. Create a deep muscle pocket for each individual fascicle 4. Plant each fascicle into a separate muscle compartment and fixate the fascicle in place with tissue glue. | Procedure or surgery | Intervention: Fascicular split |
| Targeted Muscle ReinnervationTargeted Muscle Reinnervation surgical technique 1. Painful nerve is identified and the neuroma is resected. 2. A nerve stimulator is used to identify functional motor nerve branches. Near the point where the motor branch enters the muscle, the motor nerve branch is transected 3. End-to-end nerve coaptation is performed between the amputated nerve and the transected motor nerve branch. | Procedure or surgery | Control: Targeted Muscle Reinnervation (TMR) |
Primary outcome
Phantom limb pain measured on the 11-point (0-10) numeric rating scale.
Time frame: 1 year postoperatively
A primary endpoint is the mean phantom limb pain experience one year postoperatively. This will be measured on the 11-point (0-10) numeric rating scale over 7 consecutive days. A higher score indicates worse pain.
Residual limb pain measured on the 11-point numeric rating scale
Time frame: 1 year postoperatively
A primary endpoint is the mean residual limb pain experience one year postoperatively. This will be measured on the 11-point (0-10) numeric rating scale over 7 consecutive days. A higher score indicates worse pain.
PROMIS pain behavior short form 7a
Time frame: 1 year postoperatively
PROMIS pain behavior short form 7a in Dutch-Flemish
PROMIS pain interference short form 8a
Time frame: 1 year postoperatively
PROMIS pain interference short form 8a in Dutch-Flemish
16 secondary outcomes
Phantom limb pain using the 11-point (0-10) numeric rating scale
Time frame: From enrolment until 24 months post-operatively
Residual limb pain using the 11-point (0-10) numeric rating scale
Time frame: From enrolment until 24 months postoperatively
PROMIS pain behavior 7a short form in Dutch-Flemish
Time frame: From enrolment until 24 months postoperatively
PROMIS pain interference 8a short form in Dutch-Flemish
Time frame: From enrolment until 24 months postoperatively
Quality of life (EQ-5D-5L)
Time frame: From enrolment until 24 months postoperatively
Pain type using the ICAN localization map
Time frame: From enrolment until 12 months postoperatively
Neuropathic pain using the PainDetect
Time frame: From enrolment until 12 months postoperatively
Hospital anxiety and depression using the HADS
Time frame: From enrolment until 12 months postoperatively
Perceived treatment effect using the GPE-DV
Time frame: at 12 months postoperativley
Prosthetic rehabilitation using the PLUS-M
Time frame: From enrolment until 12 months postoperatively
Changes in sensory quality in the amputated stump using quantitative sensory testing (QST)
Time frame: at enrolment until 12 months postoperative
Quantified neuroma perfusion using near-infrared fluorescence using indocyanine green
Time frame: Peri-operatively
Surgery duration
Time frame: Perioperatively
Length of hospital stay
Time frame: From the date of surgery to the date of discharge from the hospital, up to 1 year post surgery
Adverse events
Time frame: until 30 days postoperatively
Medication Quantification Scale
Time frame: until 24 months postoperatively
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 May 2026.
- BackgroundAnné C, de Laat FA, Hafner BJ, et al. "Dutch-Flemish translation of the Prosthetic Limb Users Survey of Mobility (PLUS-M)". Poster tijdens het PROMIS congres Praag. 2022.
- Background: PubMed 11124733Hudak PL, Wright JG. The characteristics of patient satisfaction measures. Spine (Phila Pa 1976). 2000 Dec 15;25(24):3167-77. doi: 10.1097/00007632-200012150-00012.
- Background: PubMed 6880820Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983 Jun;67(6):361-70. doi: 10.1111/j.1600-0447.1983.tb09716.x.
- Background: PubMed 17022849Freynhagen R, Baron R, Gockel U, Tolle TR. painDETECT: a new screening questionnaire to identify neuropathic components in patients with back pain. Curr Med Res Opin. 2006 Oct;22(10):1911-20. doi: 10.1185/030079906X132488.
- Background: PubMed 37252909Gomez-Eslava B, Raasveld FV, Hoftiezer YAJ, McCarty JC, Daddario JL, Valerio IL, Heng M, Eberlin KR. Pain Sketches to Predict Pain following Primary Targeted Muscle Reinnervation in Amputees. Plast Reconstr Surg. 2024 May 1;153(5):1162-1171. doi: 10.1097/PRS.0000000000010762. Epub 2023 May 26.
- Background: PubMed 21479777Herdman M, Gudex C, Lloyd A, Janssen M, Kind P, Parkin D, Bonsel G, Badia X. Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L). Qual Life Res. 2011 Dec;20(10):1727-36. doi: 10.1007/s11136-011-9903-x. Epub 2011 Apr 9.
- Background: PubMed 15943958Harden RN, Weinland SR, Remble TA, Houle TT, Colio S, Steedman S, Kee WG; American Pain Society Physicians. Medication Quantification Scale Version III: update in medication classes and revised detriment weights by survey of American Pain Society Physicians. J Pain. 2005 Jun;6(6):364-71. doi: 10.1016/j.jpain.2005.01.350.
- Background: PubMed 24402179Terwee CB, Roorda LD, de Vet HC, Dekker J, Westhovens R, van Leeuwen J, Cella D, Correia H, Arnold B, Perez B, Boers M. Dutch-Flemish translation of 17 item banks from the patient-reported outcomes measurement information system (PROMIS). Qual Life Res. 2014 Aug;23(6):1733-41. doi: 10.1007/s11136-013-0611-6. Epub 2014 Jan 9.
- Background: PubMed 39507316Schafer B, Freund G, Orr J, Nolte K, Weis J, Bahm J, Beier JP. Technique and Expected Benefit of Intraoperative Perfusion Imaging of Peripheral Nerves. Plast Reconstr Surg Glob Open. 2024 Nov 5;12(11):e6281. doi: 10.1097/GOX.0000000000006281. eCollection 2024 Nov.
- Background: PubMed 33268236O'Brien AL, Jordan SW, West JM, Mioton LM, Dumanian GA, Valerio IL. Targeted Muscle Reinnervation at the Time of Upper-Extremity Amputation for the Treatment of Pain Severity and Symptoms. J Hand Surg Am. 2021 Jan;46(1):72.e1-72.e10. doi: 10.1016/j.jhsa.2020.08.014. Epub 2020 Oct 22.
- Background: PubMed 36864779Berger LE, Shin S, Haffner ZK, Huffman SS, Spoer DL, Sayyed AA, Franzoni G, Bekeny JC, Attinger CE, Kleiber GM. The application of targeted muscle reinnervation in lower extremity amputations: A systematic review. Microsurgery. 2023 Oct;43(7):736-747. doi: 10.1002/micr.31030. Epub 2023 Mar 2.
- Background: PubMed 11690728Farrar JT, Young JP Jr, LaMoreaux L, Werth JL, Poole MR. Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain. 2001 Nov;94(2):149-158. doi: 10.1016/S0304-3959(01)00349-9.
- Individual participant dataSharing planned: Undecided. Undecided
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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.
Justus L. Groen, MD, PhD principal investigator
Leiden University Medical Center
1 site 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 Leiden University Medical Center at 1 site in Netherlands.
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 2 inclusion and 4 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: looking for participants now, as of the sponsor's last update on 26 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Guus A.H. Tendijck, MD (+316 21320645, g.tendijck@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phantom limb pain measured on the 11-point (0-10) numeric rating scale. (time frame: 1 year postoperatively). The study lists 4 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 NCT07605754, which also lists 20 linked publications.
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 26 May 2026.