Surgical Treatments for Post-amputation Pain in Amputees
Study Details
Study Description
Brief Summary
This is a double-blind randomised controlled trial (RCT) which compares the effectivness of three surgical techniques for alliviating neuroma pain, stump pain and phantom limb pain. The three surgical treatments are Targeted Muscles Reinnervation (TMR), Regenerative Peripheral Nerve Interface (RPNI), and an active control (neuroma transposition). Patients will be follow-up for 5 years.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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N/A |
Detailed Description
Neuroma pain, stump pain, and phantom limb pain (PLP) can develop after the loss of a body part and fall within the umbrella term post-amputation pain. However, the underlaying causes to post-amputation pain are diverse and must be addressed accordingly. Surgical treatments for neuroma pain 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 double-blind RCT will take place at Sahlgrenska University Hospital, Mölndal, Sweden. Seventy-five persons suffering from neuroma pain, stump pain or PLP, who are suitable for a surgical approach to manage this pain, will be recruited and randomly assigned to one of the surgical treatments (TMR, RPNI or control) in an allocation ratio of 1:1:1 (n=25 per group). Each participant will be followed-up in the short-term (1-, 3-, 6-, 12-months post-surgery) and in the long-term (3- and 5-years post-surgery). After the 12-months follow-up, the study will be unblinded for the evaluator and the participants. At this time, if a participant experiences no change in pain or is unsatisfied with the result, further treatment will be discussed with the clinical investigator.
The study design is chosen to be able to follow neuroma pain, stump pain and phantom limb pain intensity before and after surgical treatment as well as to investigate how pain develops up to five years post-surgery. The evaluation methods in the study are based on previously used methods in the literature for neuroma-, stump- and PLP-related pain research. The questionnaires are previously used in clinical settings.
This project will be conducted at the Center for Bionics and Pain Research (CBPR), which is an interdisciplinary collaboration between Chalmers University of Technology (Chalmers), Sahlgrenska University Hospital (SU), and the University of Gothenburg (GU).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Targeted Muscle Reinnervation (TMR) In this surgical procedure, the residual peripheral nerve is transferred to an available muscle in the stump that has been deinnervated from its native nerve. The surgical procedure includes three core steps: preparation of the residual nerve; motor nerve identification from the targeted muscle; and coaptation. To prepare the residual nerve, the surgeon identifies the injured nerve that has developed a painful neuroma and cuts the nerve back to healthy fascicles. Next, the surgeon dissects the motor nerve to a nearby target and thereby denervates a native muscle. Lastly, the injured nerve where the neuroma was excised is transferred and coapted to the newly severed motor nerve stump innervating the targe muscle. The surgery time is approximately 2-3 hours and it takes place in the hospital. The patient can leave the hospital the same day. |
Procedure: Targeted Muscle Reinnervation (TMR)
Surgical procedure used to rewire injured proximal nerves to motor nerves directly innervating an otherwise redundant target muscle.
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| Active Comparator: Regenerative Peripheral Nerve Interface (RPNI) The RPNI procedure involves construction of a residual peripheral nerve split into several nerve fascicles and implanted into free skeletal muscle grafts. The surgeon first identifies the injured nerve and excises the terminal neuroma. Then, this peripheral nerve is transected into several intraneural fascicles. Next, autologous muscle grafts are harvested from a healthy donor site and the transected nerve endings are placed in the middle part of each muscle graft, in parallel to the muscle fibres. The muscle graft is wrapped around the distal transected nerve ending and anchored by epimysial sutures, and an RPNI is created. This is repeated for each group of fascicles obtained from splitting a transected nerve. The surgery time is approximately 2-3 hours and it takes place in the hospital. The patient can leave the hospital the same day. |
Procedure: Regenerative Peripheral Nerve Interface (RPNI)
Surgical procedure where the injured nerve is split into fascicles and wrapped in free muscle grafts.
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| Active Comparator: Standard neuroma treatment, neuroma transposition The standard neuroma treatment, also called neuroma transposition, includes excision of the terminal neuroma and burying the nerve into an adjacent deep muscle. As in the TMR and RPNI procedure, the surgeon starts with finding the injured nerve and excises the terminal neuroma into healthy fascicles. Next, the surgeon identifies a deep nearby muscle which is away from joint motion and has limited output opportunities for the nerve. The nerve is then channelled inside to the deep muscle without applying any tension on it and secured by sutures. The surgery time is approximately 1-2 hours and it takes place in the hospital. The patient can leave the hospital the same day. |
Procedure: Standard neuroma treatment, neuroma transposition
Surgical procedure without any nerve reconstruction, where the injured nerve is buried in an adjacent deep muscle.
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Outcome Measures
Primary Outcome Measures
- Neuroma pain intensity [12-months post-surgery]
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-months follow-up visit.
Secondary Outcome Measures
- Stump pain intensity [12-months post-surgery]
Difference in stump 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.
- Phantom limb pain (PLP) intensity [12-months post-surgery]
Difference in PLP 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.
Eligibility Criteria
Criteria
Inclusion Criteria:
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The participant must have a major limb amputation.
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The participant is ≥ 18 years old at the time of consent.
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The participant must be in generally good health to undergo a surgical treatment, as per the clinical investigator's opinion.
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The post-operative amputation follow-up is greater than one year at time of consent.
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The participant must be diagnosed with neuroma pain, stump pain, or phantom limb in their residual limb, at latest the time of screening visit.
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The participant must have an average pain score (of neuroma pain, sump pain or PLP) greater than three on the Numerical Rating Scale (NRS, 0-10) after the baseline period.
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If the participant is prescribed pharmacological treatments for pain, there must be no variations in dosage (steady consumption) for at least one month before the screening visit.
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If the participant is prescribed non-pharmacological treatments for pain, such as spinal cord stimulation, transcutaneous electrical nerve stimulation or mirror therapy, the treatment must have ended at least one month before the screening visit.
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The participant has sufficient understanding of Swedish or English to be able to participate in all study assessments, as per the principal investigator's opinion.
Exclusion Criteria:
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Neurological or other conditions that affect nerve regeneration.
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Active infection in the residual limb.
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Smokers or less than six weeks of smoking cessation at inclusion.
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Mental inability, reluctance or language difficulties that result in difficulty understanding the meaning of study participation, as per the principal investigator's discretion.
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Ongoing participation in a clinical study that the clinical investigator deems detrimental to participation in this study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Center for Bionics and Pain Research, CBPR | Mölndal | Västra Götaland | Sweden | 431 80 |
Sponsors and Collaborators
- Chalmers University of Technology
- Sahlgrenska University Hospital, Sweden
- Göteborg University
Investigators
- Principal Investigator: Max Ortiz Catalan, PhD, Chalmers University of Technology
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- 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.
- 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.
- 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.
- 2021-02346