Neoplasms

All Conditions

Nervous System Diseases

Neuroma

Nerve Sheath Neoplasms

Neoplasms, Nerve Tissue

Neoplasms by Histologic Type

Anti-Arrhythmia Agents

Channel Blockers

Central Nervous System Depressants

All Drugs and Chemicals

Lidocaine

The control group received traditional amputation.The proximal nerve is blocked with lidocaine and cut off. The end of the nerve retracted as far as possible and the bleeding point is ligated if necessary.

The experimental group received regenerative peripheral nerve interface（RPNI） surgery.

Each RPNI unit consists of nerve stump and free autologous muscle graft that is cut off from healthy muscle of the amputated limb. The muscle graft is approximately 30×15×5 mm.The ends of the transected nerve are placed within the muscle belly of the free muscle grafts in an orientation that is parallel to the muscle fibers. Next, the nerve is secured distally with 6-0 non-absorbable monofilament sutures in an epimysial-to-epineurial fashion. The nerve is then wrapped around completely via muscle graft and epimysial securing sutures. All RPNI units are placed in areas remote from the surgical incision and from the weight-bearing surface of the limb.

preventive regenerative peripheral nerve interface reconstruction

Guangxue Li

The trial will be carried out in Peking University People's Hospital. The whole trial will last 3 years. Amputees from orthopedics and vascular surgery will be distributed into two groups randomly and receive different treatments including traditional resection and regenerative peripheral nerve interface(RPNI) surgery.The pain outcome,the impact of post-amputation pain on life and the utilization rate of prostheses will be collected to study the efficacy, safety and prognosis of preventive regenerative peripheral nerve interface reconstruction in amputees.

Investigators believe that RPNI can effectively reduce the incidence of post-amputation pain, reduce the degree of pain, improve the wearing rate of prostheses, and help patients return to normal life.

The investigator who perform the operations cannot be blinded because of the use of manual techniques.

The Efficacy of Preventive Regenerative Peripheral Nerve Interface(RPNI) Reconstruction in Amputees

The Efficacy, Safety and Prognosis of Preventive Regenerative Peripheral Nerve Interface(RPNI) Reconstruction in Amputees: Study Protocol for a Cohort Study

Patient-Reported Outcomes Measurement Information System (NRS, PROMIS) were used to assess postamputation pain.The intensity of pain is described by 11 points from 0 (painless) to 10 (the most severe pain).

Whether the subject wears a prosthetic limb, and if so, what kind of prosthetic limb is worn.

Whether there is tumor recurrence or metastasis.

The medical outcomes study-short from(MOS-SF 36) is used to evaluate the difference between the RPNIs group and the control group in the quality of life after amputation.The SF-36 scale consists of 36 questions with eight dimensions:physiological function, role-physiological, physical pain, general health, vitality, social function, role-emotional, and mental health. The scoring method was used for each dimension, ranging from 0 to 100 points. The higher the score, the better the health status.

Peking University People's Hospital

Deputy Chief Physician

In this arm, participants will have an initial surgery to place partial muscle grafts on the amputated nerves. After a healing period, the participant will have a shorter surgical procedure to implant the electrodes onto the muscle grafts and in residual muscles. After another healing period, experiments with prosthetic control and sensory feedback will begin.

In this arm, participants have already had partial muscle grafts placed on the amputated nerves to control neuroma growth. The participant will have a short surgical procedure to implant the electrodes onto the muscle grafts and in residual muscles. After a healing period, experiments with prosthetic control and sensory feedback will begin.

The device, a bipolar percutaneous intramuscular electromyography electrode, is intended for use in upper-limb amputation patients who have received the regenerative peripheral nerve interface surgical procedure, in order to enable the use of advanced prosthetic arms and hands.

a bipolar percutaneous intramuscular electromyography electrode

Paul Cederna, M.D.

Mona Moore

This is a single center, 10 subject early feasibility study in which the primary objective is to ensure the safety of percutaneous intramuscular electrodes implanted in surgically-created RPNI constructs (free muscle grafts attached to the amputated nerves) in subjects with upper limb amputation. The secondary objectives are to assess the efficacy of the electrodes in recording electromyographic signals from the RPNI grafts and in delivering electrical stimulation to the RPNI grafts to evoke sensory percepts.

This study will enroll people who have had upper limb amputations or are planning to have upper limb amputations. Each participant who does not already have RPNI grafts at the time of enrollment will have RPNI grafts implanted on branches or fascicles of nerves of the upper extremity. Several or all RPNI grafts will have a single bipolar electrode implanted in the muscle tissue, with the proximal end tunneled to a percutaneous exit point on the residual limb. Additional electrodes may be placed in innervated muscles in the residual limb, in order to provide a control comparison as well as to provide additional input during prosthesis control experiments. Electrodes will remain implanted for up to 7 years, with a minimum of 2 study visits per month to perform prosthesis control and sensory feedback experiments. Study endpoint will be assessed at a minimum of once per month while electrodes remain implanted. After a maximum of 7 years, electrodes will be explanted and the study ended after a 1 week follow-up.

The results of this study will inform the final design of the electrodes to be implanted long-term in RPNI grafts to provide an increased number of degrees of freedom for prosthetic control and sensory and proprioceptive feedback. This will drastically improve the functionality of the prosthesis, enhance the sense of embodiment of the prosthesis itself, and enable future investigation of a fully-implanted (non-percutaneous) prosthesis control system.

Short-term Implanted Electrodes Following Regenerative Peripheral Nerve Surgery for Improving Prosthetic Limb Control Signals

Pain will be assessed using the SF-36 survey instrument, to be filled out by the participant before and after each surgical procedure performed and at a minimum of once per month while electrodes remain implanted. Two questions related to pain with a score closer to 0 means a pain increase

Pain will be assessed using the LANSS survey instrument, to be filled out by the participant before and after each surgical procedure performed and at a minimum of once per month while electrodes remain implanted. A score greater than 12 indicates neuropathic pain.

Phantom pain will be assessed using the Phantom Limb Questionnaire, to be filled out by the participant before and after each surgical procedure performed and at a minimum of once per month while electrodes remain implanted. This 9-item instrument measures phantom pain on a scale of 0-4, where 0-no pain at all and 4=very severe pain.

RPNI tissue degeneration will be assessed by changes in pain scores (see above) and measurements of recording efficacy.

Recording efficacy will be assessed using two signal quality measures:

1. Peak-to-peak signal amplitude during maximum voluntary contraction
2. Signal-to-noise ratio during maximum voluntary contraction

Electrode migration outside of the implanted RPNI graft or muscle will be assessed by changes in recording efficacy, as described above, and by ultrasound examination as necessary. Electrode extrusion and implantation complications will be assessed by adverse events reported by both the participant and the study physicians. At each study visit, the participant will be asked to report any issues, and will have a basic examination of the affected limb performed by study physicians and/or trained staff.

Efficacy will be assessed, for each implanted electrode using two calculated signal quality measures: Peak-to-peak signal amplitude during maximum voluntary contraction and signal-to-noise ratio during maximum voluntary contraction.

Stimulation data will be recorded at least once per month while electrodes remain implanted. Stimulation threshold will be determined using the range of sensory feedback necessary to evoke a sensory percept.

National Institute of Neurological Disorders and Stroke (NINDS)

University of Michigan

Robert Oneal Professor and Chief of Plastic Surgery; Professor, Biomedical Engineering

Subjects will receive Intravenous ICG to generate a Fluorescence Angiogram of the Neuroma

Intravenous administration of indocyanine green followed by fluorescence angiography imaging of the neuroma

Indocyanine green

Gregory A Dumanian, MD

The purpose of this study is to characterize the perfusion of neuromas using indocyanine green fluorescence angiography

Neuromas represent the frustrated regeneration of injured nerve axons encased in a bulbous scar. Symptomatic neuromas are particularly problematic in patients with amputations. Targeted Muscle Reinnervation is a novel surgical approach to neuroma treatment, resulting in improved residual limb pain in amputees. Nevertheless, a subset of Targeted Muscle Reinnervation patients achieve inadequate relief. Incomplete neuroma excision may be of particular concern in such cases, as failure to completely excise the neuroma risks leaving a scarred proximal nerve stump behind. Despite the critical importance of complete neuroma excision, there is no clear definition of a neuroma's "zone of injury". Indeed, intraoperatively determining where to cut a nerve to ensure accurate and complete excision of a neuroma at the time of reconstruction or repair is an unsolved problem in peripheral nerve surgery. The proposed research aims to characterize the perfusion of neuromas using fluorescence angiography. Specifically, we will test the hypothesis that intravascular indocyanine green (ICG) renders visible the perturbations in nerve perfusion associated with neuromas, and that these altered perfusion patterns correlate with the nerve's "zone of injury" as identified by histopathology. Ultimately, indocyanine green (ICG) fluorescence angiography may facilitate intraoperative decision-making at the time of neuroma excision.

Evaluation of Neuroma Perfusion With Indocyanine Green Fluorescence Angiography

Individual Participant Data that underlie results in a publication

Nerve Tissue Perfusion as visualized by Fluorescence Angiogram

American Society for Surgery of the Hand

Northwestern University

Chief of Plastic surgery in the Department of Surgery

Symptoms and General Pathology

Behaviors and Mental Disorders

Pain

Phantom Limb

Perceptual Disorders

Neurobehavioral Manifestations

Neurologic Manifestations

Pain, Postoperative

Postoperative Complications

Standard Post-Amputation Surgical Care: Briefly, the transected nerves will be blindly tucked into surrounding bulky soft tissue to protect the nerve ends before the wound is closed.

Briefly, each transected nerve is identified after amputation using 6-0 Prolene suture and is dissected proximally for length. With minimal dissection, a nerve stimulator is used to identify functional motor nerve branches. Near the point where the motor branch enters the muscle, the motor nerve branch is transected and an end-to-end coaptation is performed with a nearby tagged amputated nerve.

Briefly, a muscle graft (usually from the amputated limb) is wrapped around the clean ends of the transected nerve(s).

Targeted Muscle Re-innervation involves re-routing transected nerve ends to functional motor nerves proximal to the site of amputation.

Targeted Muscle Re-innervation

Regenerative Peripheral Nerve Interface involves placing transected nerve ends in harvested muscle grafts.

Regenerative Peripheral Nerve Interface

Standard post-amputation surgical care involves placing transected nerve ends into muscle/soft tissue proximal to the site of amputation.

Standard Post-Amputation Surgical Care

Deborah Noble

The purpose of this study is to analyze the efficacy of novel interventions in post-amputation surgical care (specifically Targeted Muscle Reinnervation and Regenerative Peripheral Nerve Interface) on post-amputation pain and functional outcomes at the time of amputation. These novel interventions have been shown to be successful in treating the downstream effects of amputations (pain, phantom limb pain, neuroma pain, etc.), but has not been studied in a randomized manner at the time of amputation.

The investigators plan a randomized control trial of all eligible patients undergoing major limb amputation at Parkland Memorial Hospital. Eligible patients undergoing an amputation will be consented for all possible interventions and randomized to either receive Targeted Muscle Re-Innervation (TMR), Regenerative Peripheral Nerve Interface (RPNI), or standard post-amputation surgical care at the time of their operation. Key pre-operative data including patient sex, age, BMI, past medical history, past surgical history, medications, allergies, social history, social support systems, exposure to narcotic medication, and reason for amputation will be analyzed. Intra-operatively, patients randomized to the treatment arm will receive TMR or RPNI and the transected nerve ends addressed will be recorded. Post-operative data that will be recorded include hospital stay, complications related to the procedure, complications leading to reoperation, functional results, need for pain medication, incidence of phantom limb pain, incidence of painful neuromas, length of follow-up, and all adverse events/complications. Analyses will be conducted using data obtained from patient medical records from the Parkland Health \& Hospital System.

Effect of Prophylactic TMR and RPNI on Neuroma and Phantom Limb Pain

Prophylactic Treatment of Neuroma and Phantom Limb Pain With Targeted Muscle Reinnervation (TMR) and Regenerative Peripheral Interface (RPNI) at the Time of Major Limb Amputation: A Randomized Control Trial

The primary outcome measure of the study will the incidence of phantom limb pain in each group over the course of the recovery period.

Pain intensity score is measured bv PROMIS (Patient Reported Outcomes Measurement Information System) Scores via patient questionnaires administered at follow-up visits. Possible scores range from 1-5 where higher scores indicate worse outcome (pain severity).

Pain interference score as measured by PROMIS (Patient Reported Outcomes Measurement information System) scores via patient questionnaires administered at follow-up visits. Possible scores range from 1-5, where higher scores indicate worse outcome (pain interference).

Pain behavior score measured by PROMIS (Patient Reported Outcomes Measurement Information System) questionnaire that pertains to subject social health. Raw summed score from 8 to 40, where 40 represents severely maladaptive pain behavior.

Narcotic medical use post-operatively as measured by MME (Morphine Milligram Equivalent) Score This is a tool to condense and standardize the patient's narcotic pain regimen.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
The Efficacy of Preventive Regenerative Peripheral Nerve Interface(RPNI) Reconstruction in Amputees	NCT05554900	Amputation Neur...	preventive rege...	6 Years -	Peking University People's Hospital
Short-term Implanted Electrodes Following Regenerative Peripheral Nerve Surgery for Improving Prosthetic Limb Control Signals	NCT03260400	Amputation Neur... Amputation	a bipolar percu...	22 Years - 65 Years	University of Michigan
Evaluation of Neuroma Perfusion With Indocyanine Green Fluorescence Angiography	NCT06164392	Neuroma Neuroma Amputat... Neuroma of Uppe... Neuroma of Lowe...	Indocyanine gre...	18 Years -	Northwestern University
Effect of Prophylactic TMR and RPNI on Neuroma and Phantom Limb Pain	NCT05344261	Amputation Neuroma Amputat... Phantom Limb Pa... Residual Limbs	Targeted Muscle... Regenerative Pe... Standard Post-A...	18 Years -	University of Texas Southwestern Medical Center
Effect of Prophylactic TMR and RPNI on Neuroma and Phantom Limb Pain	NCT05344261	Amputation Neuroma Amputat... Phantom Limb Pa... Residual Limbs	Targeted Muscle... Regenerative Pe... Standard Post-A...	18 Years -	University of Texas Southwestern Medical Center

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