Surgical Treatments for Postamputation Pain

Phantom Limb Pain Clinical Trial

Official title:

Surgical Treatments for Postamputation Pain

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05009394
• Other study ID #: 2021-02346
• Status: Recruiting
• Phase: N/A
• Start date: June 20, 2023
• Est. completion date: June 2028

Study information

• Verified date: September 2023
• Source: Center for Bionics and Pain Research
• Contact: Emily Pettersen, MSc
• Phone: +46764026503
• Email: emily.pettersen[@]vgregion.se
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Residual limb pain (RLP), neuroma pain, and phantom limb pain (PLP) can develop after the loss of a body part and fall within the umbrella term postamputation pain. However, the underlaying causes to postamputation pain are diverse and must be addressed accordingly. Surgical treatments for RLP have become a popular approach and have shown great potential for successful outcomes. The two surgical interventions, Targeted Muscle Reinnervation (TMR) and Regenerative Peripheral Nerve Interface (RPNI), are globally used in pain management therapies. This is a multi-centre, double-blind, superiority RCT which takes place at 9 hospitals in 7 countries:the Sahlgrenska University Hospital in Gothenburg, Sweden; the Rizzoli Orthopaedic Institute in Bologna, Italy; the University of Alberta Hospital in Edmonton, Canada; Worker Hospital in Santiago, Chile; the NHS Lothian, NHS Clyde & Greater Glasgow, and NHS Grampian, UK; Dandenong Hospital, Monash Health in Melbourne, Australia; the Northwestern Memorial Hospital in Chicago, USA; the University of Michigan Health System in Ann Arbor, Michigan, USA; and within the Massachusetts General Hospital in Boston, USA. One hundred ten participants will be recruited and randomly assigned to one of three surgical treatments (TMR, RPNI, or control) in an equal allocation ratio (n = 37 per group). Each participant will be followed up short term (1, 3, 6, and 12 months post-surgery) and long term (2 and 4 years post-surgery). After the 12-month follow-up, the study will be unblinded for the evaluator and the participants. If the participants are unsatisfied with the outcome of the treatment, they may request one of the other treatments. In such a case, a medical evaluation and further treatment options will be discussed in consultation with the clinical investigator at the site. The study design is chosen to be able to follow RLP, neuroma pain and PLP intensity before and after surgical treatment as well as to investigate how pain develops up to four years post-surgery. The evaluation methods in the study are based on previously used methods in the literature for RLP-, neuroma- and PLP-related pain research. The questionnaires are previously used in clinical settings.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 110
• Est. completion date: June 2028
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Amputation Neuroma
• Neuralgia
• Neuroma
• Pain, Nerve
• Pain, Neuropathic
• Phantom Limb
• Phantom Limb Pain
• Residual Limb Pain

Intervention

Procedure:
• Targeted Muscle Reinnervation (TMR)
Surgical procedure used to rewire injured proximal nerves to motor nerves directly innervating an otherwise redundant target muscle.
• Regenerative Peripheral Nerve Interface (RPNI)
Surgical procedure where the the nerve is split into fascicles and wrapped in free muscle grafts.
• Standard neuroma treatment, neuroma excision, and muscle burying
Surgical procedure where the neuroma is excised and the nerve stump is buried in an adjacent deep muscle.

Locations

Country	Name	City	State
Australia	Dandenong Hospital, Monash Health	Melbourne
Canada	University of Alberta Hospital	Edmonton	Alberta
Chile	Worker Hospital	Santiago
Italy	Rizzoli Orthopedic Institute	Bologna	Emilia-Romagna
Sweden	Sahlgrenska University Hospital	Mölndal	Västra Götaland
United Kingdom	NHS Lothian, NHS Clyde & Greater Glasgow, and NHS Grampian	Edinburgh
United States	University of Michigan Health System	Ann Arbor	Michigan
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Northwestern Memorial Hospital	Chicago	Illinois

Sponsors (15)

Lead Sponsor	Collaborator
Center for Bionics and Pain Research	Chalmers University of Technology, Dandenong Hospital, Göteborg University, Hospital del Trabajador de Santiago, Istituto Ortopedico Rizzoli, Massachusetts General Hospital, NHS Grampian, NHS Greater Clyde and Glasgow, NHS Lothian, Northwestern Memorial Hospital, The Bionics Institute of Australia, University of Alberta, University of Michigan, Vastra Gotaland Region

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Chile,  Italy,  Sweden,  United Kingdom, 

References & Publications (8)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Neuroma pain intensity	Difference in neuroma 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	Phantom limb pain intensity	Difference in phantom 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-months follow-up visit.	Baseline to12-month post-surgery