Clinical trial NCT05009394: Surgical Treatments for Postamputation Pain
Official title: Surgical Treatments for Postamputation Pain
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Residual Limb Pain
Amputation Neuroma
Phantom Limb Pain
Pain, Neuropathic
Pain, Nerve
Lead sponsor: Prometei Pain Rehabilitation Center
Sponsor class: OTHER
Collaborators: name: Vastra Gotaland Region
name: Göteborg University
name: Istituto Ortopedico Rizzoli
name: Hospital del Trabajador de Santiago
name: NHS Lothian
name: NHS Greater Clyde and Glasgow
name: NHS Grampian
name: Northwestern Memorial Hospital
name: University of Michigan
name: Massachusetts General Hospital
name: Dandenong Hospital
name: University of Alberta
First posted: 2021-08-17
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Residual limb pain intensity
timeFrame: Baseline to 12-month post-surgery
Secondary outcomes:
measure: Neuroma pain intensity
timeFrame: Baseline to 12-month post-surgery
measure: Phantom limb pain intensity
timeFrame: Baseline to12-month post-surgery
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
city: Melbourne
country: Australia
facility: Dandenong Hospital, Monash Health
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Santiago
country: Chile
facility: Worker Hospital
city: Bologna
country: Italy
facility: Rizzoli Orthopedic Institute
state: Emilia-Romagna
city: Mölndal
country: Sweden
facility: Sahlgrenska University Hospital
state: Västra Götaland
city: Edinburgh
country: United Kingdom
facility: NHS Lothian, NHS Clyde & Greater Glasgow, and NHS Grampian
Study officials:
affiliation: Prometei Pain Rehabilitation Center
name: Max Ortiz Catalan, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.
citation: 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.
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.
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.