Surgical Treatments for Postamputation Pain

NCT05009394 | Recruiting

• 1 other identifier: 2021-02346
• Study Type: interventional
• Target: 110
• Locations: 7 countries
• Sites: 9

Brief Summary

This is a double-blind randomised controlled trial (RCT) which compares the effectiveness of three surgical techniques for alleviating residual limb pain (RLP), neuroma pain and phantom limb pain (PLP). The three surgical treatments are Targeted Muscles Reinnervation (TMR), Regenerative Peripheral Nerve Interface (RPNI), and an active control (neuroma excision and muscle burying). Patients will be follow-up for 4 years.

Conditions

Residual Limb Pain; Amputation Neuroma; Phantom Limb Pain; Pain, Neuropathic; Pain, Nerve

Outcome Measures

Primary Outcomes (1)

• Residual limb pain intensity

  Difference in residual limb pain intensity will be measured by numerical rating scale (NRS, 0-10), where 0 - no pain and 10 - worst imaginable pain, between baseline period and at the 12-month follow-up visit.

  Baseline to 12-month post-surgery

Secondary Outcomes (2)

• Neuroma pain intensity

  Baseline to 12-month post-surgery

• Phantom limb pain intensity

  Baseline to12-month post-surgery

Study Arms (3)

Targeted Muscle Reinnervation (TMR)

ACTIVE COMPARATOR

The surgical procedure comprises three steps: preparation of the donor nerve, identification of a motor branch to the targeted muscle, and nerve coaptation. To prepare the donor nerve, the surgeon will identify the nerve with a painful neuroma and resect the neuroma up to healthy fascicles. Next, the surgeon will identify a motor branch to a nearby target muscle and will confirm muscle contraction using a hand-held nerve stimulator. The motor branch to the target muscle will be transected as close as possible to its entry point without tension. In the final step, the previous nerve stump from which the neuroma was resected will be transferred and coapted to the newly severed motor branch that innervates the target muscle and secured by 2-3 non-resorbable monofilament sutures. The surgery time is approximately 2-3 hours and it takes place in the hospital.

Procedure: Targeted Muscle Reinnervation (TMR)

Regenerative Peripheral Nerve Interface (RPNI)

ACTIVE COMPARATOR

The RPNI procedure involves construction of a residual peripheral nerve split into several nerve fascicles and implanted into free skeletal muscle grafts. First, the surgeon identifies the nerve with a painful neuroma and resect the neuroma up to healthy fascicles. Then, a longitudinal intraneural dissection will be performed exposing its fascicles. Next, autologous muscle grafts will be harvested from a healthy donor site, and the dissected nerve stumps will be placed parallel to the muscle fibers. The nerve stump will be secured to the muscle graft, thereafter the graft will be wrapped around the nerve stump and anchored in the folded graft, thus creating an RPNI. This will be repeated for each fascicle obtained from splitting the transected nerve. Lastly, the RPNIs will be placed in a protected area. The surgery time is approximately 2-3 hours and it takes place in the hospital.

Procedure: Regenerative Peripheral Nerve Interface (RPNI)

Standard neuroma treatment, neuroma excision, and muscle burying

ACTIVE COMPARATOR

The standard neuroma treatment, also called neuroma transposition, includes excision of the terminal neuroma and burying the nerve into an adjacent deep muscle.The standard neuroma treatment entails the excision of the terminal neuroma and then implanting the nerve into an adjacent muscle. Firstly, the surgeon will identify the nerve with a painful neuroma and thereafter resect the neuroma up to healthy fascicles. Next, the surgeon will identify a nearby muscle which is not involved in joint motion and has limited output opportunities for the nerve. The nerve will then be channeled at least 1 cm inside the muscle without applying any tension to it and secured by 1-2 non-resorbable monofilament sutures. The identified nerve with the painful neuroma will not be treated with any additional therapy than the resection (e.g., diathermy, pharmacotherapy, crushing, etc.). The surgery time is approximately 1-2 hours and it takes place in the hospital.

Procedure: Standard neuroma treatment, neuroma excision, and muscle burying

Interventions

Targeted Muscle Reinnervation (TMR) PROCEDURE

Surgical procedure used to rewire injured proximal nerves to motor nerves directly innervating an otherwise redundant target muscle.

Targeted Muscle Reinnervation (TMR)

Regenerative Peripheral Nerve Interface (RPNI) PROCEDURE

Surgical procedure where the the nerve is split into fascicles and wrapped in free muscle grafts.

Regenerative Peripheral Nerve Interface (RPNI)

Standard neuroma treatment, neuroma excision, and muscle burying PROCEDURE

Surgical procedure where the neuroma is excised and the nerve stump is buried in an adjacent deep muscle.

Standard neuroma treatment, neuroma excision, and muscle burying

Eligibility Criteria

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

You may qualify if:

• The participant must have a major limb amputation.
• The participant is ≥ 18 years old at the time of consent.
• The participant must be in generally good health to undergo a surgical intervention, as per the clinical investigator's opinion.
• Time since the last amputation must be over a year at the time of consent.
• The participant must have an average residual limb pain score equal or greater than 4 on the Numerical Rating Scale (NRS, 0-10) after the baseline period.
• If the participant has been prescribed pharmacological treatments for pain, there must be no variations in dosage (steady consumption) for at least 1 month before the screening visit.
• If the participant has been prescribed non-pharmacological treatments for pain, such as spinal cord stimulation, transcutaneous electrical nerve stimulation, and mirror therapy, the treatment must have ended at least 1 month before the screening visit.
• The participant must have a stable prosthetic fitting for at least a month before the screening visit.
• The participant has a sufficient understanding of the language in which the assessments will be conducted, as per the clinical investigator's opinion.

You may not qualify if:

• Neurological or other conditions that affect nerve regeneration for the nerve to be treated.
• Active infection in the residual limb.
• Prior RPNI or TMR surgery of the nerve to be treated (with painful neuroma) to address postamputation pain.
• Mental disorders (e.g., schizophrenia, paranoia, psychosis, etc.), reluctance, or language difficulties that result in difficulty understanding the meaning of study participation.
• Ongoing participation in a clinical study that the clinical investigator deems detrimental to participation in this study.

Sponsors & Collaborators

• Prometei Pain Rehabilitation Center: lead
• Vastra Gotaland Region: collaborator
• Göteborg University: collaborator
• Istituto Ortopedico Rizzoli: collaborator
• Hospital del Trabajador de Santiago: collaborator
• NHS Lothian: collaborator
• NHS Greater Clyde and Glasgow: collaborator
• NHS Grampian: collaborator
• Northwestern Memorial Hospital: collaborator
• University of Michigan: collaborator
• Massachusetts General Hospital: collaborator
• Dandenong Hospital: collaborator
• University of Alberta: collaborator

Study Sites (9)

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

NOT YET RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

NOT YET RECRUITING

University of Michigan Health System

Ann Arbor, Michigan, 48109, United States

NOT YET RECRUITING

Dandenong Hospital, Monash Health

Melbourne, Australia

NOT YET RECRUITING

University of Alberta Hospital

Edmonton, Alberta, AB T6G 2B7, Canada

NOT YET RECRUITING

Worker Hospital

Santiago, Chile

NOT YET RECRUITING

Rizzoli Orthopedic Institute

Bologna, Emilia-Romagna, 40136, Italy

RECRUITING

Sahlgrenska University Hospital

Mölndal, Västra Götaland County, 431 80, Sweden

NOT YET RECRUITING

NHS Lothian, NHS Clyde & Greater Glasgow, and NHS Grampian

Edinburgh, United Kingdom

NOT YET RECRUITING

Related Publications (10)

• Dumanian 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.

  PMID: 30371518 BACKGROUND

• Souza JM, Cheesborough JE, Ko JH, Cho MS, Kuiken TA, Dumanian GA. Targeted muscle reinnervation: a novel approach to postamputation neuroma pain. Clin Orthop Relat Res. 2014 Oct;472(10):2984-90. doi: 10.1007/s11999-014-3528-7.

  PMID: 24562875 BACKGROUND

• Woo SL, Kung TA, Brown DL, Leonard JA, Kelly BM, Cederna PS. Regenerative Peripheral Nerve Interfaces for the Treatment of Postamputation Neuroma Pain: A Pilot Study. Plast Reconstr Surg Glob Open. 2016 Dec 27;4(12):e1038. doi: 10.1097/GOX.0000000000001038. eCollection 2016 Dec.

  PMID: 28293490 BACKGROUND

• Pettersen E, Sassu P, Reinholdt C, Dahm P, Rolfson O, Bjorkman A, Innocenti M, Pedrini FA, Breyer JM, Roche A, Hart A, Harrington L, Ladak A, Power H, Hebert J, Ortiz-Catalan M. Surgical treatments for postamputation pain: study protocol for an international, double-blind, randomised controlled trial. Trials. 2023 May 2;24(1):304. doi: 10.1186/s13063-023-07286-0.

  PMID: 37131180 BACKGROUND

• Chang BL, Mondshine J, Attinger CE, Kleiber GM. Targeted Muscle Reinnervation Improves Pain and Ambulation Outcomes in Highly Comorbid Amputees. Plast Reconstr Surg. 2021 Aug 1;148(2):376-386. doi: 10.1097/PRS.0000000000008153.

  PMID: 34398088 BACKGROUND

• Bjorklund KA, Alexander J, Tulchin-Francis K, Yanes NS, Singh S, Valerio I, Klingele K, Scharschmidt T. Targeted Muscle Reinnervation for Limb Amputation to Avoid Neuroma and Phantom Limb Pain in Patients Treated at a Pediatric Hospital. Plast Reconstr Surg Glob Open. 2023 Apr 13;11(4):e4944. doi: 10.1097/GOX.0000000000004944. eCollection 2023 Apr.

  PMID: 37063502 BACKGROUND

• Kubiak CA, Kemp SWP, Cederna PS, Kung TA. Prophylactic Regenerative Peripheral Nerve Interfaces to Prevent Postamputation Pain. Plast Reconstr Surg. 2019 Sep;144(3):421e-430e. doi: 10.1097/PRS.0000000000005922.

  PMID: 31461024 BACKGROUND

• Valerio IL, Dumanian GA, Jordan SW, Mioton LM, Bowen JB, West JM, Porter K, Ko JH, Souza JM, Potter BK. Preemptive Treatment of Phantom and Residual Limb Pain with Targeted Muscle Reinnervation at the Time of Major Limb Amputation. J Am Coll Surg. 2019 Mar;228(3):217-226. doi: 10.1016/j.jamcollsurg.2018.12.015. Epub 2019 Jan 8.

  PMID: 30634038 BACKGROUND

• Pettersen E, Sassu P, Pedrini FA, Granberg H, Reinholdt C, Breyer JM, Roche A, Hart A, Ladak A, Power HA, Leung M, Lo M, Valerio I, Eberlin KR, Ko J, Dumanian GA, Kung TA, Cederna P, Ortiz-Catalan M. Regenerative Peripheral Nerve Interface: Surgical Protocol for a Randomized Controlled Trial in Postamputation Pain. J Vis Exp. 2024 Mar 15;(205). doi: 10.3791/66378.

  PMID: 38557950 DERIVED

• Pettersen E, Sassu P, Pedrini FA, Granberg H, Reinholdt C, Breyer JM, Roche A, Hart A, Ladak A, Power HA, Leung M, Lo M, Valerio I, Eberlin KR, Kung TA, Cederna P, Souza JM, Aszmann O, Ko J, Dumanian GA, Ortiz-Catalan M. Targeted Muscle Reinnervation: Surgical Protocol for a Randomized Controlled Trial in Postamputation Pain. J Vis Exp. 2024 Mar 8;(205). doi: 10.3791/66379.

  PMID: 38526122 DERIVED

MeSH Terms

Conditions

Phantom Limb; Neuralgia

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; Peripheral Nervous System Diseases; Neuromuscular Diseases

Study Officials

• Max Ortiz Catalan, PhD

  Prometei Pain Rehabilitation Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Max Ortiz Catalan, PhD

CONTACT

+46708461065; maxortizc@outlook.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 12, 2021
• First Posted: August 17, 2021
• Study Start: June 20, 2023
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2029
• Last Updated: January 9, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1); AU (1); CL (1); IT (1); SE (1); US (3); GB (1)