Alcohol Neurolysis and Capsaicin for Postamputation Pain (PAP)

NCT07443553 | Not Yet Recruiting DMC

• 2 other identifiers: UNBROKEN-1Neu-92-13337
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Postamputation pain is a complex condition that includes phantom limb pain (PLP), stump pain and residual limb pain (RLP), the latter of which may be referred from joints, the spine and inflamed bursa and tendons. PLP may have peripheral, spinal and central etiologies. The evidence of peripheral mechanisms includes the relief of both PLP and RLP during local anesthetic (LA) infusions, the relief of PLP and RLP with sympathetic blocks and neuroma injections, and the development of phantom radicular pain in amputees with a herniated disc. Neurolysis and defunctionalization are long-lasting treatments for pain when LA blocks provide temporary benefit, being most commonly used for cancer pain (e.g., celiac plexus neurolysis). Neurolysis has also been used to treat PAP, with uncontrolled studies showing benefit for both RLP and PLP. However, there are no controlled studies demonstrating efficacy. In this small study, we will evaluate the effectiveness of alcohol neurolysis of lower extremity neuromas (femoral or saphenous; sciatic or common peroneal and/or tibial; obturator and/ or lateral femoral cutaneous when pain is in those distributions) in individuals with RLP and PLP. For individuals with upper extremity amputation in whom non-selective neurolysis may affect the ability to use certain prosthetics that depend on functioning nerve and muscle signals, high-concentration capsaicin will be injected in an observational arm. The investigators will also examine factors associated with treatment outcome in a subset of patients (e.g., functional MRI, quantitative sensory testing).

Conditions

Postamputation Pain

Keywords

Postamputation pain; phantom limb pain; residual limb pain

Outcome Measures

Primary Outcomes (2)

• Average phantom limb pain

  Average phantom limb pain on 0-10 numerical rating scale (NRS)

  6 weeks

• Average residual limb pain

  Residual limb pain on 0-10 numerical rating scale (NRS)

  6 weeks after treatment

Secondary Outcomes (36)

• Phantom limb pain

  2 weeks

• Residual limb pain

  2 weeks

• Worst residual limb pain

  6 weeks

• Worst phantom limb pain

  6 weeks

• Phantom limb pain

  12 weeks

Study Arms (3)

Alcohol neurolysis

EXPERIMENTAL

Injection of 2 mL lidocaine 2% at each painful neuroma over 5 minutes, followed by 1.25-3.5 mL 98-100% dehydrated ethyl alcohol (the volume depends on the voltage threshold, i.e., thresholds \> 0.5 mL may warrant the higher volume). In those with bilateral lower extremity amputations, one leg will receive this treatment.

Procedure: Injection of alcohol near neuroma

Capsaicin

OTHER

Observational cohort for upper extremity amputees in which participants will receive 1.25-3.5 mL 150 micrograms/mL of capsaicin if they experience greater or equal to 30% pain relief after injection of 2 mL of lidocaine 2% at sites of painful neuromas.

Procedure: Injection of capsaicin 150 mcg per mL if relief with lidocaine 2%

Lidocaine only

ACTIVE COMPARATOR

Injection of 2 mL lidocaine 2% at each painful neuroma over 5 minutes, followed by 1.5 mL saline within 5 minutes.

Procedure: Lidocaine 2% injection

Interventions

Injection of alcohol near neuroma PROCEDURE

Injection of 98-100% alcohol over painful neuromas after lidocaine 2% injected.

Alcohol neurolysis

Lidocaine 2% injection PROCEDURE

Injection of Lidocaine 2% followed by normal saline

Also known as: Blinded control arm for alcohol neurolysis

Lidocaine only

Injection of capsaicin 150 mcg per mL if relief with lidocaine 2% PROCEDURE

Painful upper neuroma neuromas will be injected if patients experience at least 30% pain relief with lidocaine. These patients (upper extremity amputees) are an observational cohort.

Capsaicin

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 2. At least 1 lower extremity amputation 3. Pain duration \>/= 1 month 4. Either average RLP or PLP in one or both (for those who have 2 lower limbs enrolled) amputated extremities \>/=4/10 5. Stable analgesic regimen over the past 10 days 6. Failure of physical therapy and at least 2 pharmacological treatments 7. At least 1 suspected painful neuroma, identified by Tinel's sign or pain with pressure or prosthetic use, referred pain in the distribution of the severed nerve, and neuropathic-type symptoms (tingling, shooting or lancinating pain)

You may not qualify if:

• \. Very poorly controlled psychiatric condition (e.g., PCL-5 score \> 60, \> 15 on the anxiety and/or depression section of HADS) 2. Poorly controlled medical condition that would preclude participation (e.g., heart failure, uncontrolled diabetes) 3. Patients in whom targeted muscle reinnervation or a similar procedure is being considered 4. Systemic infection or infection overlying the stump 5. Clinically-relevant injury to nerve fibers proximal to the amputation 6. Pregnancy

Sponsors & Collaborators

• Northwestern University: lead
• First Lviv Medical Union: collaborator

Study Sites (1)

First Lviv Medical Union

Lviv, Ukraine

Location

Related Publications (2)

• Campbell CM, Diamond E, Schmidt WK, Kelly M, Allen R, Houghton W, Brady KL, Campbell JN. A randomized, double-blind, placebo-controlled trial of injected capsaicin for pain in Morton's neuroma. Pain. 2016 Jun;157(6):1297-1304. doi: 10.1097/j.pain.0000000000000544.

  PMID: 26963851 BACKGROUND

• Zhang X, Xu Y, Zhou J, Pu S, Lv Y, Chen Y, Du D. Ultrasound-guided alcohol neurolysis and radiofrequency ablation of painful stump neuroma: effective treatments for post-amputation pain. J Pain Res. 2017 Feb 3;10:295-302. doi: 10.2147/JPR.S127157. eCollection 2017.

  PMID: 28223839 BACKGROUND

MeSH Terms

Conditions

Phantom Limb

Interventions

Ethanol; Lidocaine; Injections

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Alcohols; Organic Chemicals; Acetanilides; Anilides; Amides; Aniline Compounds; Amines; Drug Administration Routes; Drug Therapy; Therapeutics

Central Study Contacts

Steven Paul Cohen, MD

CONTACT

1-312-695-2500; steven.cohen@northwestern.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Lidocaine before alcohol neurolysis (which may be painful) will be given to facilitate participant masking
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 24, 2026
• First Posted: March 2, 2026
• Study Start: February 15, 2026
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): March 31, 2029
• Last Updated: March 12, 2026

Record last verified: 2026-03

Locations

UA (1)