Results of Nerve Surgery to Treat PostAmputation Pain

NCT07605754 | Recruiting

• 1 other identifier: 25-3058
• Study Type: observational
• Target: 98
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Amputation Neuroma

Keywords

Neuroma; Amputation; pain; Targeted Muscle Reinnervation; Nerve embedding

Outcome Measures

Primary Outcomes (4)

• 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.

  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.

  1 year postoperatively

• PROMIS pain behavior short form 7a

  PROMIS pain behavior short form 7a in Dutch-Flemish

  1 year postoperatively

• PROMIS pain interference short form 8a

  PROMIS pain interference short form 8a in Dutch-Flemish

  1 year postoperatively

Secondary Outcomes (16)

• Phantom limb pain using the 11-point (0-10) numeric rating scale

  From enrolment until 24 months post-operatively

• Residual limb pain using the 11-point (0-10) numeric rating scale

  From enrolment until 24 months postoperatively

• PROMIS pain behavior 7a short form in Dutch-Flemish

  From enrolment until 24 months postoperatively

• PROMIS pain interference 8a short form in Dutch-Flemish

  From enrolment until 24 months postoperatively

• Quality of life (EQ-5D-5L)

  From enrolment until 24 months postoperatively

Study Arms (2)

Control: Targeted Muscle Reinnervation (TMR)

Patients with a symptomatic neuroma requiring surgical intervention

Procedure: Targeted Muscle Reinnervation

Intervention: Fascicular split

Patients with a symptomatic neuroma requiring surgical intervention

Procedure: Fascicular split

Interventions

Fascicular split PROCEDURE

Fasicular 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.

Also known as: nerve embedding

Intervention: Fascicular split

Targeted Muscle Reinnervation PROCEDURE

Targeted 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.

Control: Targeted Muscle Reinnervation (TMR)

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

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.

You may qualify if:

• Age older than or equal to 18 years
• Intractable postamputation pain

You may not qualify if:

• 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

Sponsors & Collaborators

• Leiden University Medical Center: lead

Study Sites (1)

Leiden University Medical Center

Leiden, South Holland, 2333 ZA, Netherlands

RECRUITING

Related Publications (20)

• 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.

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  PMID: 28678059 BACKGROUND

• Nederlandse Vereniging van Revalidatieartsen. Amputatie en prothesiologie onderste extremiteit. Available from: https://richtlijnendatabase.nl/richtlijn/amputatie_prothesiologie_onderste_extremiteit/startpagina_-_amputatie_en_prothesiologie_onderste_extremiteit.html.

  BACKGROUND

• Schwingler PM, Moman RN, Hunt C, Ashmore Z, Ogletree SP, Uvodich ME, Murad MH, Hooten WM. Prevalence of postamputation pain and its subtypes: a meta-analysis with meta-regression. Pain Rep. 2021 May 4;6(1):e918. doi: 10.1097/PR9.0000000000000918. eCollection 2021.

  PMID: 33981935 BACKGROUND

MeSH Terms

Conditions

Neuroma; Pain

Condition Hierarchy (Ancestors)

Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Neoplasms by Histologic Type; Neoplasms; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Justus L. Groen, MD, PhD

  Leiden University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Guus A.H. Tendijck, MD

CONTACT

+316 21320645; g.tendijck@hotmail.com

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: September 15, 2025
• First Posted: May 26, 2026
• Study Start: August 14, 2025
• Primary Completion (Estimated): August 20, 2028
• Study Completion (Estimated): August 20, 2029
• Last Updated: May 26, 2026

Record last verified: 2026-05

Locations

NL (1)