Surgical Treatments for Neuroma Pain in Amputees

NCT04204668 | Withdrawn

• 1 other identifier: IRB00235936
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

Amputees often suffer from relentless pain and disability resulting from symptomatic neuromas within the amputation stumps. When conservative measures fail to address these symptoms, two contemporary surgical approaches to treat symptomatic neuromas have become the most popular. Targeted muscle reinnervation (TMR) is a procedure which involves transferring the injured proximal nerve stump into a terminal nerve branch entering muscle, such that the axons from the proximal nerve stump will regenerate into the muscle and thereby prevent neuroma recurrence. Regenerative peripheral nerve interfaces (RPNIs) are muscle grafts placed on the proximal nerve stumps that serve as targets for the regenerating axons from the proximal nerve stumps. While TMR and RPNIs have demonstrated promise for the treatment of symptomatic neuromas, prospective comparative data comparing outcomes with these two approaches is lacking. The investigators have recently developed a novel approach to treat symptomatic neuromas that provides vascularized, denervated muscle targets (VDMTs) for the axons regenerating from the severed proximal nerve stump to reinnervate. This is accomplished by islandizing a segment of muscle on its blood supply and ensuring complete denervation prior to implanting the neighboring transected nerve stump into this muscle. VDMTs offer theoretical benefits in comparison to RPNIs and TMR that the investigators also aim to test in the proposed study. The investigators' objective is to enroll amputees with symptomatic neuromas into a prospective study in which amputees will be randomized to undergo TMR, RPNI, or VDMT and subsequently monitored for pain and disability for 1-year post-operatively. The investigators' specific aims are as follows: 1) Test the hypothesis that VDMTs are more effective than TMR and RPNIs with regards to treating pain and disability associated with symptomatic neuromas; 2) Provide the first level one, prospective data directly comparing the efficacy of TMR and RPNIs.

Conditions

Pain, Neuropathic; Amputation Neuroma; Phantom Limb Pain

Outcome Measures

Primary Outcomes (2)

• Worst reported residual limb pain score on a numerical scale

  Pain score will be assessed using the numerical pain score (0-10) with 0 representing no pain and 10 representing the worst pain.

  One year post-operatively

• Worst reported phantom limb pain score on a numerical scale

  Pain score will be assessed using the numerical pain score (0-10) with 0 representing no pain and 10 representing the worst pain.

  One year post-operatively

Study Arms (3)

Targeted Muscle Reinnervation (TMR)

ACTIVE COMPARATOR

In this operation, the surgeon will make a skin incision and carefully identify nerves that were likely to have been injured during the amputation surgery. These nerves are then "cleaned up" to be rerouted and connected to smaller nerves that control individual muscles. The connection to nerves that run into muscles is thought to be helpful in directing the nerve healing process and reducing the risk of developing pain in the future. This operation takes 2 - 4 hours and occurs in the hospital. Follow up requires six to seven clinic visits with the surgeon over the course of one year, at which time standard questionnaires will be used to assess pain.

Procedure: TMR

Regenerative peripheral nerve interface (RPNI)

ACTIVE COMPARATOR

In this operation, the surgeon will make a skin incision and carefully identify nerves that were likely to have been injured during the amputation surgery. The nerves are then "cleaned up" to enhance the possibility of healthy healing. Then the surgeon takes a small sample from a muscle (usually one close by to the nerves that are being operated on but sometimes through a second incision in the arm or leg, depending on the exact medical situation) and form something called a "muscle graft". The muscle graft is used to wrap the cleaned ends of the nerves mentioned above. This is thought to be helpful in directing the nerve healing process and reducing the risk of developing pain in the future. This operation takes 1 - 3 hours and occurs in the hospital. Follow up requires six to seven clinic visits with the surgeon over the course of one year, at which time standard questionnaires will be used to assess pain.

Procedure: RPNI

Vascularized, denervated muscle target (VDMT )

ACTIVE COMPARATOR

In this operation, the surgeon will make a skin incision and carefully identify nerves that were likely to have been injured during the amputation surgery. The nerves are then "cleaned up" to enhance the possibility of healthy healing. The surgeon will then identify a local muscle along with a small artery and vein that supply blood to part of the muscle. A small sample of muscle, still attached to the artery and vein, is then created. The nearby nerves are then nestled into this segment of muscle that is still connected to the artery and vein. This is thought to be helpful in directing the nerve healing process and reducing the risk of developing pain in the future. This operation takes 2 - 4 hours and occurs in the hospital. Follow up requires six to seven clinic visits with the surgeon over the course of one year, at which time standard questionnaires will be used to assess pain.

Procedure: VDMT

Interventions

TMR PROCEDURE

Surgical procedure to connect injured proximal nerve stumps to motor nerve branches directly innervating a muscle

Targeted Muscle Reinnervation (TMR)

RPNI PROCEDURE

Surgical procedure to wrap the ends of injured nerves in small muscle grafts

Regenerative peripheral nerve interface (RPNI)

VDMT PROCEDURE

Surgical procedure that creates a small muscle graft that is both denervated and vascularized, which will then receive the damaged nerve ending

Vascularized, denervated muscle target (VDMT )

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> 18 years
• Patients presenting with \> 6 months of intractable post-amputation limb pain with no history of previous surgical intervention for pain treatment.
• Patient is able to sign informed consent and able to participate in all testing associated with this clinical investigation
• Women of childbearing potential who have a negative pregnancy test

You may not qualify if:

• Age \< 18 years old
• Patient unable to sign informed consent
• Patient participating in another investigational device, surgical technique, or pharmacological study
• Prisoner or patient from vulnerable populations as defined in 45 Code of Federal Regulations (CFR) 46.

Sponsors & Collaborators

• Johns Hopkins University: lead
• The Plastic Surgery Foundation: collaborator

Study Sites (2)

Johns Hopkins Bayview Medical Center

Baltimore, Maryland, 21224, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

MeSH Terms

Conditions

Neuralgia; Phantom Limb

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Perceptual Disorders; Neurobehavioral Manifestations; Pain, Postoperative; Postoperative Complications; Pathologic Processes

Study Officials

• Sami Tuffaha, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Three arm, randomized trial

Study Record Dates

• First Submitted: December 17, 2019
• First Posted: December 19, 2019
• Study Start: April 1, 2021
• Primary Completion: February 12, 2025
• Study Completion: February 12, 2025
• Last Updated: June 3, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)