Regenerative Peripheral Nerve Interface (RPNI) for painful neuromas after lower-limb amputation

The Effect of Regenerative Peripheral Nerve Interface (RPNI) Surgery on Neuropathic Pain and Functional Outcomes in Major Lower Extremity Amputations

This project tests whether RPNI surgery reduces mechanical sensitivity and neuropathic pain and improves prosthesis comfort in adults with symptomatic neuromas after major lower-limb amputation.

Quick facts

• Study type: Observational
• Enrollment: 20 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Saglik Bilimleri Universitesi (Academic / other)
• Locations: 1 site (Ankara, Ankara)
• Trial ID: NCT07420192 on ClinicalTrials.gov

What this trial studies

This is a prospective observational cohort of adults with unilateral major lower-extremity amputations who undergo standard-of-care RPNI surgery for symptomatic neuromas. Participants are selected using a standardized Clinical Triad (validated neuropathic pain questionnaire, a localized Tinel's-trigger point, and ultrasound visualization of the neuroma). Objective mechanical hypersensitivity is measured with Pressure Pain Threshold (PPT) using a digital algometer and compared to preoperative baselines, while subjective neuropathic pain, functional mobility, and prosthesis satisfaction are tracked over 24 months. The study uses routine RPNI surgical technique with a free autologous muscle graft and follows patients longitudinally to characterize long-term outcomes.

Who should consider this trial

Good fit: Adults 18–70 with a unilateral transtibial, transfemoral, or knee-disarticulation amputation who have symptomatic neuroma confirmed by the Clinical Triad (DN4 ≥4, NRS ≥4, localized Tinel/trigger point, and ultrasound visualization) and who are scheduled for RPNI surgery are ideal candidates.

Not a fit: Patients with competing diagnoses such as Complex Regional Pain Syndrome, significant heterotopic ossification, bilateral major amputations, inability to undergo surgery, or those who do not meet the diagnostic triad are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, RPNI could reduce neuroma-related pain and mechanical hypersensitivity and improve prosthesis tolerance and mobility for lower-limb amputees.

How similar studies have performed: Smaller clinical series and case reports of RPNI have shown promising reductions in neuroma pain and improved outcomes, but long-term prospective data in lower-limb amputees remain limited.

Eligibility criteria

Inclusion Criteria:

* 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:

  1. Neuropathic Pain: DN4 Questionnaire score ≥ 4.
  2. Pain Intensity: Numeric Rating Scale (NRS) score ≥ 4.
  3. Physical Exam: Positive Tinel's sign or palpation tenderness at a specific trigger point.
  4. 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.

Exclusion Criteria:

* 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).

Where this trial is running

Ankara, Ankara

• University of Health Sciences, Gulhane Training and Research Hospital, Department of Orthopedics and Traumatology — Ankara, Ankara, Turkey (Türkiye) (Recruiting)

Study contacts

• Principal investigator: Ahmet Burak Bilekli, MD, Associate Professor — University of Health Sciences, Gülhane Training and Research Hospital
• Study coordinator: Ahmet Burak Bilekli, MD, Associate Professor

Conditions Symptomatic Neuroma; Phantom Limb Pain After Amputation; Residual Limb Pain; Neuropathic Pain; Lower Extremity Amputations; RPNI; Regenerative Peripheral Nerve Interface; Pressure Pain Threshold