Evaluation of RPNI for Symptomatic Neuromas in Lower Limb Amputees

NCT07420192 | Recruiting

• 2 other identifiers: RPNI-SBU-AMPUTEE-20262026-24
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This prospective, observational cohort study evaluates the long-term outcomes of Regenerative Peripheral Nerve Interface (RPNI) surgery in patients with major lower extremity amputations suffering from symptomatic neuromas. RPNI is a surgical technique where the transected nerve end is implanted into a free autologous muscle graft to serve as a physiological target for reinnervation. The study aims to objectively assess the reduction in mechanical hypersensitivity using Pressure Pain Threshold (PPT) measurements via a digital algometer. Additionally, it monitors subjective neuropathic pain levels, functional mobility, and prosthesis satisfaction over a 24-month follow-up period compared to pre-operative baselines.

Conditions

Neuropathic Pain; Symptomatic Neuroma; Phantom Limb Pain After Amputation; Residual Limb Pain; Lower Extremity Amputations

Keywords

RPNI; Regenerative Peripheral Nerve Interface; Pressure Pain Threshold; PPT; Algometry; Prosthesis Satisfaction; Viscero-Somatic Convergence; Phantom Motor Execution

Outcome Measures

Primary Outcomes (1)

• Change in Pressure Pain Threshold (PPT)

  Objective measurement of mechanical hypersensitivity at the neuroma site using a digital pressure algometer. The device applies increasing pressure in kg/cm² until the patient reports pain. Measurements are taken from the most tender point of the neuroma and a control point. Higher values indicate higher pain tolerance (improvement).

  Baseline (Pre-op), 3, 6, 12, and 24 months post-operation.

Secondary Outcomes (8)

• Change in Pain Intensity (NRS)

  Baseline, 3, 6, 12, and 24 months.

• Change in Neuropathic Pain Characteristics (DN4 Score)

  Baseline, 3, 6, 12, and 24 months.

• Prosthesis Satisfaction and Quality of Life (PEQ)

  Baseline, 3, 6, 12, and 24 months.

• Change in Functional Mobility (TUG Test)

  Baseline, 3, 6, 12, and 24 months.

• Daily Prosthesis Usage Time (DPUT)

  Baseline, 3, 6, 12, and 24 months.

Other Outcomes (2)

• Charlson Comorbidity Index (CCI)

  Baseline (Pre-op) only.

• Elixhauser Comorbidity Index (ECI)

  Baseline (Pre-op) only.

Study Arms (1)

RPNI Group

Adult patients (18-70 years) with unilateral major lower extremity amputations (transtibial or transfemoral) who are diagnosed with "Symptomatic Neuroma" confirmed by the clinical triad (DN4 score ≥4, positive Tinel sign, and diagnostic ultrasound). These patients are scheduled to undergo Regenerative Peripheral Nerve Interface (RPNI) surgery as part of the routine standard of care treatment protocol.

Procedure: Regenerative Peripheral Nerve Interface (RPNI) Surgery

Interventions

Regenerative Peripheral Nerve Interface (RPNI) Surgery PROCEDURE

The surgical procedure is standardized as follows to preserve the residual limb (stump) anatomy: * Approach: An 8-10 cm incision is made on the lateral thigh. For transtibial (below-knee) amputees, the incision is placed approximately 15 cm proximal to the knee joint. For transfemoral (above-knee) amputees, it is placed 5-10 cm proximal to the distal end of the residual limb. * Nerve Dissection: The sciatic nerve is isolated, dissected, and transected at its most distal point. Subsequently, it is separated into the Common Peroneal and Tibial divisions. * Fascicular Separation: Based on nerve thickness, intraneural dissection is performed to split the Common Peroneal nerve into 1 or 2 fascicles, and the Tibial nerve into 2 to 4 fascicles. * Graft Harvesting: Autologous muscle grafts are harvested to wrap these created fascicles. The donor site is standardized by amputation level: Vastus Lateralis muscle for transtibial amputees and Biceps Femoris muscle for transfemoral amputees.

RPNI Group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adult patients with major lower extremity amputations presenting to the tertiary Orthopedics and Traumatology clinic with complaints of chronic residual limb pain, phantom limb pain, and prosthesis intolerance, who are diagnosed with symptomatic neuroma and scheduled for surgical intervention.

You may qualify if:

• Age: Adults aged 18 to 70 years.
• Amputation Status: Unilateral major lower extremity amputation (Transtibial, Transfemoral, or Knee Disarticulation).
• Radiological Baseline: Absence of Heterotopic Ossification (HO) in the residual limb, confirmed by pre-operative X-rays (Walter Reed Classification Grade 0).
• Diagnosis: Confirmed diagnosis of "Symptomatic Neuroma" validated by the Clinical Triad:
• Neuropathic Pain: DN4 Questionnaire score ≥ 4.
• Pain Intensity: Numeric Rating Scale (NRS) score ≥ 4.
• Physical Exam: Positive Tinel's sign or palpation tenderness at a specific trigger point.
• Radiology: Diagnostic Ultrasound visualization of the neuroma bulb.
• Surgical Indication: Scheduled for RPNI surgery as part of the routine standard of care treatment protocol due to prosthesis intolerance or severe pain.
• Consent: Willing and able to provide informed consent and attend follow-up visits.

You may not qualify if:

• CRPS: Diagnosis of Complex Regional Pain Syndrome (CRPS Type 1 or 2).
• Concurrent Bone Surgery: Patients requiring simultaneous stump revision surgery (e.g., bone shortening, osteotomy, spur excision) or having existing HO (Walter Reed Grade \> 0).
• Systemic Conditions: Uncontrolled diabetes mellitus (HbA1c \> 8.5%) or severe peripheral arterial disease compromising wound healing.
• Cognitive Status: Cognitive impairment or psychiatric conditions preventing reliable completion of patient-reported outcome measures (PEQ, DN4).
• History: Previous RPNI surgery at the same site (Recurrent RPNI cases).

Sponsors & Collaborators

• Saglik Bilimleri Universitesi: lead

Study Sites (1)

University of Health Sciences, Gulhane Training and Research Hospital, Department of Orthopedics and Traumatology

Ankara, Ankara, 06018, Turkey (Türkiye)

RECRUITING

Related Publications (13)

• Yuan M, Gallo M, Gallo L, Huynh MH, McRae M, McRae MC, Thoma A, Coroneos CJ, Voineskos SH. Targeted Muscle Reinnervation and Regenerative Peripheral Nerve Interfaces Versus Standard Management in the Treatment of Limb Amputation: A Systematic Review and Meta-Analysis. Plast Surg (Oakv). 2024 May;32(2):253-264. doi: 10.1177/22925503221107462. Epub 2022 Jun 16.

  PMID: 38681253 BACKGROUND

• Watson CPN, Midha R, Ng DW. Causalgia: A Review of Nerve Resection, Amputation, Immunotherapy, and Amputated Limb CRPS II Pathology. Can J Neurol Sci. 2024 May;51(3):351-356. doi: 10.1017/cjn.2023.260. Epub 2023 Jul 25.

  PMID: 37489506 BACKGROUND

• Vaskov A, Wallace D, Desai K, Laidlaw A, Kung T, Gates D, Kemp S, Chestek C, Cederna P. A Robust Neuromuscular Interface to Restore Lost Function in People with Amputations. Res Sq [Preprint]. 2025 May 14:rs.3.rs-5989030. doi: 10.21203/rs.3.rs-5989030/v1.

  PMID: 40470247 BACKGROUND

• Senger JL, Thorkelsson A, Wang BY, Chan KM, Kemp SWP, Webber CA. Comparison of 2 Regenerative Peripheral Nerve Interface Techniques for the Treatment of Rat Neuroma Pain. Plast Reconstr Surg. 2024 Aug 1;154(2):346-349. doi: 10.1097/PRS.0000000000010911. Epub 2023 Jul 4.

  PMID: 37400949 BACKGROUND

• Raasveld FV, Lehle CH, Hwang CD, Cross RE, Husseini JS, Simeone FJ, Newman ET, Tuano K, Lozano-Calderon SA, Valerio IL, Eberlin KR. The influence of nerve surgical techniques at time of amputation on the prevalence of heterotopic ossification in transtibial amputees. Injury. 2025 Feb;56(2):112047. doi: 10.1016/j.injury.2024.112047. Epub 2024 Nov 20.

  PMID: 39608134 BACKGROUND

• Pettersen E, Sassu P, Pedrini FA, Granberg H, Reinholdt C, Breyer JM, Roche A, Hart A, Ladak A, Power HA, Leung M, Lo M, Valerio I, Eberlin KR, Ko J, Dumanian GA, Kung TA, Cederna P, Ortiz-Catalan M. Regenerative Peripheral Nerve Interface: Surgical Protocol for a Randomized Controlled Trial in Postamputation Pain. J Vis Exp. 2024 Mar 15;(205). doi: 10.3791/66378.

  PMID: 38557950 BACKGROUND

• Lin Z, Yu P, Chen Z, Li G. Regenerative peripheral nerve interface reduces the incidence of neuroma in the lower limbs after amputation: a retrospective study based on ultrasound. J Orthop Surg Res. 2023 Aug 24;18(1):619. doi: 10.1186/s13018-023-04116-6.

  PMID: 37620955 BACKGROUND

• Lans J, Groot OQ, Hazewinkel MHJ, Kaiser PB, Lozano-Calderon SA, Heng M, Valerio IL, Eberlin KR. Factors Related to Neuropathic Pain following Lower Extremity Amputation. Plast Reconstr Surg. 2022 Aug 1;150(2):446-455. doi: 10.1097/PRS.0000000000009334. Epub 2022 Jul 27.

  PMID: 35687412 BACKGROUND

• Best CS, Cederna PS, Kung TA. Regenerative Peripheral Nerve Interface (RPNI) Surgery for Mitigation of Neuroma and Postamputation Pain. JBJS Essent Surg Tech. 2024 Feb 12;14(1):e23.00009. doi: 10.2106/JBJS.ST.23.00009. eCollection 2024 Jan-Mar.

  PMID: 38348364 BACKGROUND

• Lauzon JC, Boyd KU, Dudek NL. What to expect following targeted muscle reinnervation/regenerative peripheral nerve interface: Pain outcomes in an amputee population. J Plast Reconstr Aesthet Surg. 2024 Dec;99:373-376. doi: 10.1016/j.bjps.2024.10.017. Epub 2024 Oct 13.

  PMID: 39426252 BACKGROUND

• Kubiak CA, Kemp SWP, Cederna PS. Regenerative Peripheral Nerve Interface for Management of Postamputation Neuroma. JAMA Surg. 2018 Jul 1;153(7):681-682. doi: 10.1001/jamasurg.2018.0864. No abstract available.

  PMID: 29847613 BACKGROUND

• Hu Y, Ursu DC, Sohasky RA, Sando IC, Ambani SLW, French ZP, Mays EA, Nedic A, Moon JD, Kung TA, Cederna PS, Kemp SWP, Urbanchek MG. Regenerative peripheral nerve interface free muscle graft mass and function. Muscle Nerve. 2021 Mar;63(3):421-429. doi: 10.1002/mus.27138. Epub 2020 Dec 20.

  PMID: 33290586 BACKGROUND

• de Lange JWD, Hundepool CA, Power DM, Rajaratnam V, Duraku LS, Zuidam JM. Prevention is better than cure: Surgical methods for neuropathic pain prevention following amputation - A systematic review. J Plast Reconstr Aesthet Surg. 2022 Mar;75(3):948-959. doi: 10.1016/j.bjps.2021.11.076. Epub 2021 Dec 5.

  PMID: 34955394 BACKGROUND

MeSH Terms

Conditions

Neuralgia

Interventions

Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Ahmet Burak Bilekli, MD, Associate Professor

  University of Health Sciences, Gülhane Training and Research Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ahmet Burak Bilekli, MD, Associate Professor

CONTACT

+905326007020; draburakbilekli@yahoo.com

Muhammed Burak Polat, MD

CONTACT

+90 545 340 73 23; draburakbilekli@yahoo.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 24 Months
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: February 12, 2026
• First Posted: February 19, 2026
• Study Start: January 20, 2026
• Primary Completion (Estimated): November 1, 2029
• Study Completion (Estimated): March 1, 2030
• Last Updated: February 19, 2026

Record last verified: 2026-02

Locations

TU (1)