TMR + RPNI for Amputation-Related Pain
Recruiting in Palo Alto (17 mi)
Overseen byMargaret S Roubaud
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: M.D. Anderson Cancer Center
Disqualifiers: Under 18, Non-oncologic amputation, others
No Placebo Group
Trial Summary
What is the purpose of this trial?
This clinical trial evaluates two surgical techniques (targeted muscle re-innervation \[TMR\] and regenerative peripheral nerve interfaces \[RPNI\]) alone and in combination for the alleviation of chronic residual limb and phantom limb pain in cancer patients who have had an amputation. Chronic residual limb pain and phantom limb pain are debilitating outcomes of traumatic and oncologic amputation. Emerging microsurgical treatments for post-amputation pain are very promising. TMR and RPNI are both approved surgical techniques that involve connecting cut nerves to parts of the muscle as a way to heal and protect the nerves. This trial evaluates these techniques alone and in combination for the treatment of residual and phantom limb pain in cancer patients who have received an amputation.
Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.
What data supports the effectiveness of the treatment Regenerative Peripheral Nerve Interface Surgery, Targeted Muscle Reinnervation for amputation-related pain?
Is TMR + RPNI safe for humans?
TMR (Targeted Muscle Reinnervation) and RPNI (Regenerative Peripheral Nerve Interface) have been used to help reduce pain after amputations, and they are generally considered safe. These techniques have been shown to improve pain outcomes and quality of life for amputee patients, with no major safety concerns reported in the studies.12567
How does the TMR + RPNI treatment for amputation-related pain differ from other treatments?
The TMR + RPNI treatment is unique because it combines two advanced surgical techniques to provide new targets for nerve growth, potentially reducing pain from amputated nerves. This approach not only helps in pain reduction but also enhances nerve regeneration and muscle reinnervation, which is not typically addressed by standard treatments.128910
Eligibility Criteria
This trial is for cancer patients who have chronic pain after limb amputation. Participants should be experiencing residual or phantom limb pain. Specific eligibility criteria are not provided, but typically include factors like overall health status and time since amputation.Inclusion Criteria
Patients able to complete informed consent
I have nerves in my amputation stump or reconstructed area that can be used for surgery.
I am 18 or older and getting an amputation due to cancer.
Exclusion Criteria
I am unable to give consent by myself.
I have not had an amputation for immediate relief with a life expectancy under 3 months.
I am under 18 years old.
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Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Surgical Treatment
Participants undergo one of the surgical procedures: TMR, RPNI, or TMR combined with RPNI
1 week
Follow-up
Participants are monitored for safety and effectiveness after the surgical treatment
12 months
Follow-up visits at 3, 6, and 12 months
Treatment Details
Interventions
- Regenerative Peripheral Nerve Interface Surgery (Procedure)
- Targeted Muscle Reinnervation (Procedure)
Trial OverviewThe study tests two surgical techniques: Targeted Muscle Reinnervation (TMR) and Regenerative Peripheral Nerve Interface Surgery (RPNI), both alone and combined, to see if they reduce chronic pain in the remaining limb or phantom sensation post-amputation.
Participant Groups
3Treatment groups
Experimental Treatment
Active Control
Group I: Arm 3 (TMI + RPNI)Experimental Treatment3 Interventions
Patients undergo TMR in combination with RPNI.
Group II: Arm 2 (regenerative peripheral nerve interface)Active Control2 Interventions
Patients undergo RPNI procedure.
Group III: Arm 1 (targeted muscle reinnervation)Active Control2 Interventions
Patients undergo TMR procedure.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
M D Anderson Cancer CenterHouston, TX
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Who Is Running the Clinical Trial?
M.D. Anderson Cancer CenterLead Sponsor
References
Targeted Muscle Reinnervation Combined with a Vascularized Pedicled Regenerative Peripheral Nerve Interface. [2020]Symptomatic neuromas and pain caused by nerve transection injuries can adversely impact a patient's recovery, while also contributing to increased dependence on opioid and other pharmacotherapy. These sources of pain are magnified following amputation surgeries, inhibiting optimal prosthetic wear and function. Targeted muscle reinnervation (TMR) and regenerative peripheral nerve interfaces (RPNI) represent modern advances in addressing amputated peripheral nerves. These techniques offer solutions by essentially providing neuromuscular targets for transected peripheral nerves "to grow into and reinnervate." Recent described benefits of these techniques include reports on pain reduction or ablation (eg, phantom limb pain, residual limb pain, and/or neuroma pain).1-6 We describe a technical adaptation combining TMR with a "pedicled vascularized RPNI (vRPNI)." The TMR with the vRPNI surgical technique described offers the advantage of having a distal target nerve and a target muscle possessing deinnervated motor end plates which may potentially enhance nerve regeneration and muscle reinnervation, while also decreasing amputated nerve-related pain.
Practice Patterns and Pain Outcomes for Targeted Muscle Reinnervation: An Informed Approach to Targeted Muscle Reinnervation Use in the Acute Amputation Setting. [2022]Targeted muscle reinnervation (TMR) and regenerative peripheral nerve interface (RPNI) procedures have been shown to improve patient-reported outcomes for the treatment of symptomatic neuromas after amputation; however, the specific indications and comparative outcomes of each are unclear. The primary research questions were what complement of nerves most frequently requires secondary pain intervention after conventional amputation, whether this information can guide the focused application of TMR and RPNI to the primary amputation setting, and how the outcomes compare in both settings.
Prophylactic Regenerative Peripheral Nerve Interfaces to Prevent Postamputation Pain. [2022]Postamputation pain affects a large number of individuals living with major limb loss. Regenerative peripheral nerve interfaces are constructs composed of a transected peripheral nerve implanted into an autologous free muscle graft. The authors have previously shown that regenerative peripheral nerve interfaces can be used to treat symptomatic end neuromas that develop after major limb amputation. In this study, they investigated the potential of prophylactic interfaces to prevent the formation of symptomatic neuromas and mitigate phantom limb pain.
Peripheral Nerve Management in Extremity Amputations. [2022]The effective management of peripheral nerves in amputation surgery is critical to optimizing patient outcomes. Nerve-related pain after amputation is common, maybe a source of dissatisfaction and functional impairment, and should be considered in all amputees presenting with pain and dysfunction. While traction neurectomy or transposition has long been the standard of care, both regenerative peripheral nerve interface (RPNI) and targeted muscle reinnervation (TMR) have emerged as promising techniques to improve neuroma-related and phantom pain. A multi-disciplinary and multi-modal approach is essential for the optimal management of amputees both acutely and in the delayed or chronic setting.
TMRpni: Combining Two Peripheral Nerve Management Techniques. [2020]Amputee patients suffer high rates of chronic neuropathic pain, residual limb dysfunction, and disability. Recently, targeted muscle reinnervation (TMR) and regenerative peripheral nerve interface (RPNI) are 2 techniques that have been advocated for such patients, given their ability to maximize intuitive prosthetic function while also minimizing neuropathic pain, such as residual and phantom limb pain. However, there remains room to further improve outcomes for our residual limb patients and patients suffering from symptomatic end neuromas. "TMRpni" is a nerve management technique that leverages beneficial elements described for both TMR and RPNI. TMRpni involves coaptation of a sensory or mixed sensory/motor nerve to a nearby motor nerve branch (ie, a nerve transfer), as performed in traditional TMR surgeries. Additionally, the typically mismatched nerve coaptation is wrapped with an autologous free muscle graft that is akin to an RPNI. The authors herein describe the "TMRpni" technique and illustrate a case where this technique was employed.
Combined TMR and RPNI in a vasculopathy patient: A case report. [2023]TMR (targeted muscle reinnervation) or RPNI (regenerative peripheral nerve interface) have been the standard after nerve injuries. In this case report, we explain our approach in combining these two techniques (TMRpni) for a patient undergoing left above-the-knee amputation. Using this method, both phantom and nerve pain were reduced in our patient's case. As this technique becomes more well understood and widely adopted, amputee patients may achieve a greater quality of life post operation.
Risk Factors for Neuropathic Pain Following Major Upper Extremity Amputation. [2023]Active treatment (targeted muscle reinnervation [TMR] or regenerative peripheral nerve interfaces [RPNIs]) of the amputated nerve ends has gained momentum to mitigate neuropathic pain following amputation. Therefore, the aim of this study is to determine the predictors for the development of neuropathic pain after major upper extremity amputation.
A Direct Comparison of Targeted Muscle Reinnervation and Regenerative Peripheral Nerve Interfaces to Prevent Neuroma Pain. [2023]Targeted muscle reinnervation (TMR) and regenerative peripheral nerve interface (RPNI) surgeries manage neuroma pain; however, there remains considerable discord regarding the best treatment strategy. We provide a direct comparison of TMR and RPNI surgery using a rodent model for the treatment of neuroma pain.
Effects of regenerative peripheral nerve interface on dorsal root ganglia neurons following peripheral axotomy. [2022]Long-term delayed reconstruction of injured peripheral nerves always results in poor recovery. One important reason is retrograde cell death among injured sensory neurons of dorsal root ganglia (DRG). A regenerative peripheral nerve interface (RPNI) was capable of generating new synaptogenesis between the proximal nerve stump and free muscle graft. Meanwhile, sensory receptors within the skeletal muscle can also be readily reinnervated by donor sensory axons, which allows the target muscles to become sources of sensory information for function reconstruction. To date, the effect of RPNI on injured sensory neurons is still unclear. Here, we aim to investigate the potential neuroprotective role of RPNI on sensory DRG neurons after sciatic axotomy in adult rats.
Efficacy of Biological and Physical Enhancement on Targeted Muscle Reinnervation. [2022]Targeted muscle reinnervation (TMR) is a microsurgical repair technique to reconstruct the anatomical structure between the distal nerve and the muscle stump to provide more myoelectric information to the artificially intelligent prosthesis. Postoperative functional electrical stimulation treatment of the patient's denervated muscle or proximal nerve stump as well as nerve growth factor injection is effective in promoting nerve regeneration and muscle function recovery. In this experiment, we successfully established a TMR rat model and divided Sprague-Dawley (SD) adult male rats into TMR group, TMR + FES group, and TMR + NGF group according to TMR and whether they received FES treatment or NGF injection after surgery, and the recovery effect of rat neuromuscular function was assessed by analyzing EMG signals. Through the experiments, we confirmed that growth factor supplementation and low-frequency electrical stimulation can effectively promote the regeneration of the transplanted nerve as well as significantly enhance the motor function of the target muscle and have a positive effect on the regeneration of the transplanted nerve.