Prevention of PostAmputation Pain With Targeted Muscle Reinnervation

NCT06719245 | Recruiting DMC

• 1 other identifier: NL87196.058.24
• Study Type: interventional
• Target: 203
• Locations: 1 country
• Sites: 7

Brief Summary

The goal of this study is to compare postamputation pain (phantom limb pain and residual limb pain) one year postoperatively in patients who received a lower extremity amputation (LEA) with standard nerve handling (neurectomy) versus those who received Targeted Muscle Reinnervation (TMR). Patients between 18 and 75 years old, scheduled for an LEA (transfemoral to transtibial) as a primary or secondary sequela of vascular disease, are randomized into standard neurectomy or TMR. TMR is a frequently studied surgical technique and prevents neuroma formation by rerouting a cut mixed nerve end to a functional motor nerve. The investigators hypothesize that TMR during amputation surgery will significant improve PostAmputation Pain (PAP), quality of life, participation in family life and society, and reduction of health-related costs. Participants will be asked to complete multiple online questionnaires postoperatively regarding these outcomes at five evaluation moments (at 2 weeks, and at 3, 6, 9, and 12 months).

Conditions

Amputation, Surgical; Phantom Limb Pain; Neuroma Amputation; Surgery

Keywords

TMR; Amputation; Phantom pain; Neuroma

Outcome Measures

Primary Outcomes (4)

• Postoperative residual limb pain

  Postoperative residual limb pain will be scored on the 11-point (0-10) Numeric Rating Scale (NRS) for 30 consecutive days in a pain diary. A higher score indicates more pain.

  at 12 months

• Postoperative phantom limb pain

  Postoperative phantom limb pain will be scored on the 11-point (0-10) Numeric Rating Scale (NRS) for 30 consecutive days in a pain diary. A higher score indicates more pain.

  at 12 months

• Postoperative pain behavior

  Postoperative pain behavior will be scored using the Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Behavior Short Form 7a. The results will be scored on a scale from 7 to 35 points, with a higher score indicating that pain has a greater influence on behavior.

  at 12 months

• Postoperative pain interference

  Postoperative pain interference will be scored using the Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference Short Form 8a. The results will be scored on a scale from 8 to 40 points, where a higher score indicates greater interference of pain with daily life

  at 12 months

Secondary Outcomes (15)

• Postoperative residual limb pain

  at 3, 6, and 9 months

• Postoperative phantom limb pain

  at 3, 6, and 9 months

• Postoperative pain behavior

  at 3, 6, and 9 months

• Postoperative pain interference

  at 3, 6, and 9 months

• Neuropathic pain

  at 12 months

Other Outcomes (3)

• Surgical time

  at 0 months

• Length of hospital stay

  at 0 months

• Adverse events

  30 days postoperative

Study Arms (2)

Standard Neurectomy (control)

OTHER

Standard Neurectomy during amputation (control)

Procedure: Standard neurectomy

Targeted Muscle Reinnervation (intervention)

OTHER

Targeted Muscle Reinnervation (TMR) during amputation (intervention)

Procedure: Targeted Muscle Reinnervation (TMR)

Interventions

Targeted Muscle Reinnervation (TMR) PROCEDURE

In short: each transected nerve is identified after amputation and is dissected proximally for length. 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 and an end-to-end coaptation is performed with a nearby amputated nerve.

Targeted Muscle Reinnervation (intervention)

Standard neurectomy PROCEDURE

During the amputation a standard neurectomy will be performed based on the surgeons preference. Standard neurectomy will include cutting of the nerve, with or without traction, with or without coagulation, and with or without infiltration with a local anesthetic (i.e., ropivacaine) or phenol. Ligation of the nerve will not be allowed.

Standard Neurectomy (control)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged between 18 and 75 years old.
• Scheduled for a transtibial, through-knee, or transfemoral amputation as a primary or secondary sequela of vascular disease.

You may not qualify if:

• Insensate limbs at the level of amputation.
• Complex Regional Pain Syndrome.
• Existing neuroma or prior neuroma surgery in the affected limb.
• Undergoing radiotherapy on the affected limb.
• Cognitive impairment, or delirium at the time of consent.
• Patients who are unfit for general anesthesia.
• No nerve surgeon trained in the TMR procedure is available

Sponsors & Collaborators

• Leiden University Medical Center: lead
• Alrijne Hospital: collaborator
• Medical Center Haaglanden: collaborator
• ZonMw: The Netherlands Organisation for Health Research and Development: collaborator
• UMC Utrecht: collaborator
• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): collaborator
• Erasmus Medical Center: collaborator
• Isala: collaborator

Study Sites (7)

Amsterdam University Medical Center

Amsterdam, North Holland, 1105 AZ, Netherlands

NOT YET RECRUITING

Isala Zwolle

Zwolle, Overijssel, 8025 AB, Netherlands

NOT YET RECRUITING

Leiden University Medical Center

Leiden, South Holland, 2333 ZA, Netherlands

RECRUITING

Alrijne Zorggroep

Leiderdorp, South Holland, 2353 GA, Netherlands

NOT YET RECRUITING

Erasmus Medical Center

Rotterdam, South Holland, 3015 GD, Netherlands

NOT YET RECRUITING

Haaglanden Medisch Centrum

The Hague, South Holland, 2512 VA, Netherlands

NOT YET RECRUITING

University Medical Center Utrecht

Utrecht, Utrecht, 3584 CX, Netherlands

NOT YET RECRUITING

Related Publications (26)

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Related Links

• Study coordinating center

MeSH Terms

Conditions

Phantom Limb; Neuroma

Condition Hierarchy (Ancestors)

Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Pain, Postoperative; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain; Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Justus L Groen, MD PhD

  Leiden University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Justus L Groen, Md PhD

CONTACT

+31715262109; j.l.groen@lumc.nl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD PhD

Study Record Dates

• First Submitted: July 12, 2024
• First Posted: December 5, 2024
• Study Start: December 31, 2024
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028
• Last Updated: September 19, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: After completion of the study, the key file will be archived in the hospital's study documentation on a protected location on the network hard drive for 15 years in accordance with article 17 of the European good clinical practice directive.
• Access Criteria: Before acquiring the deidentified individual patient data used in the results of the published work related to this protocol (incl. tables, figures, supplementary files), researcher must sign a data sharing agreement. Data will made available to those who submit a reasonable request with a methodologically sound proposal.

Locations

NL (7)