Preoperative (Pre-amputation) Cryoanalgesia to Improve Post-amputation Phantom Limb Pain

Preoperative (Pre-amputation) Cryoanalgesia to Improve Post-amputation Phantom Limb Pain, General Physical and Emotional Disability, and Opioid Consumption: a Randomized Pilot Trial

Investigators will evaluate preamputation cryoanalgesia on pain, mobility, opioid use and general physical and emotional disability using a pilot randomized trial design, to explore the amount and variability of improvement on those outcomes and to investigate the potentiality of conducting a future larger randomized controlled trial, which the investigators will assess quantitatively the benefits of cryoanalgesia.

Study Overview

• Status: Withdrawn
• Conditions: Postoperative Pain
• Intervention / Treatment: Device: Cryoanalgesia; Device: Sham Cryoanalgesia

Detailed Description

Primary Aim: To determine preoperative cryoneurolysis improves phantom limb pain compared with no cryoneurolysis. Estimate the standard deviation of phantom limb pain score at baseline and post-treatment (Day 0), Days 1 and 2; Weeks 1, 2, 3, and Months 1, 2 and 3. The investigators will consider using the upper limit of the 75% confidence interval to plan the sample size of future larger trial.

Hypothesis 1: Preoperative cryoneurolysis reduces phantom limb pain over 3 month after surgical leg amputation compared with no cryoneurolysis.

Secondary Aim 1: To determine if preoperative cryoneurolysis improves mobility after lower limb amputation compared with no cryoneurolysis.

Hypothesis 1: Preoperative cryoneurolysis improves mobilization (as measured with accelerometer) over 3 the month after surgical leg amputation compared with no cryoneurolysis.

Secondary Aim 2: To determine if preoperative cryoneurolysis improves general physical and emotional disability after lower limb amputation compared with no cryoneurolysis.

Hypothesis 2: Preoperative cryoneurolysis reduces general physical and emotional disability (as measured with the World Health Organization Disability Assessment) over the 3 month after surgical leg amputation compared with no cryoneurolysis.

Secondary Aim 3: To determine if preoperative cryoneurolysis decreases opioid use after lower limb amputation compared with no cryoneurolysis.

Hypothesis 3: Preoperative cryoneurolysis reduces opioid consumption over the 3 month after surgical leg amputation compared with no cryoneurolysis.

Exploratory Aims:

Hypothesis 1: Preoperative cryoneurolysis reduces residual limb pain over the 3 months after surgical leg amputation compared with no cryoneurolysis.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults at least 18 years of age.
• Scheduled for a unilateral lower limb amputation distal to the femoral head and including at least one metatarsal bone.

Exclusion Criteria:

• Pregnancy
• Incarceration
• Morbid obesity (body mass index greater than 40 kg/m2
• Contraindication specific to cryoneurolysis such as a localized infection at the treatment site, cryoglobulinemia, cold urticaria, or Reynaud's syndrome.
• Investigator opinion that the potential subject is a poor candidate for this trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cryoanalgesia; Participants will receive cryoanalgesia with the The iovera° system.	Device: Cryoanalgesia; Participants will receive cryoanalgesia with the The iovera° system. . The specific nerves targeted will be both the sciatic, targeted first (as distal as possible, but not more distal than the bifurcation), and femoral, targeted second (as distal as possible, but not more distal than the adductor canal). Cryoanalgesia will result from an 8-minute-long percutaneous cryoneuroablation procedure consisting of several freeze/defrost cycles. Per routine, all patients will have a nerve block with single shot ropivacaine.
Sham Comparator: Sham Cryoanalgesia; Participants will receive Sham cryoanalgesia with the The iovera° system.	Device: Sham Cryoanalgesia; Participants will receive Sham cryoanalgesia with the The iovera° system. The specific nerves targeted will be both the sciatic, targeted first (as distal as possible, but not more distal than the bifurcation), and femoral, targeted second (as distal as possible, but not more distal than the adductor canal). Per routine, all patients will have a nerve block with single shot ropivacaine.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phantom limb pain score	Pain scores ranging from 0 - "no pain" to 10 - "worst pain ever" over 3 month after surgical leg amputation.	3 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mobility	Number of steps measured with accelerometer integrated into the Fitbit Inspire 3 Health &-Fitness-Tracker) over 3 the month after surgical leg amputation compared with no cryoneurolysis.	3 Months
General physical and emotional disability	General physical and emotional disability measured with the World Health Organization Disability Assessment. Level of disability is described as none (0-0.49), mild (0.5-1.49), moderate (1.5-2.49), severe (2.5-3.49), or extreme (3.5-4).	3 Months
Opioid consumption	Opioid consumption measured by Morphine Equivalent Doses over 3 months after surgical leg amputation.	3 Months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Residual limb pain	Pain scores ranging from 0 - "no pain" to 10 - "worst pain ever" over 3 month after surgical leg amputation.	3 Months

Collaborators and Investigators

• Sponsor: The Cleveland Clinic
• Collaborators: Pacira Pharmaceuticals, Inc
• Investigators: Principal Investigator: Alparslan Turan, MD, The Cleveland Clinic

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2024
• Primary Completion (Actual): September 10, 2024
• Study Completion (Actual): September 10, 2024

Study Registration Dates

• First Submitted: January 30, 2024
• First Submitted That Met QC Criteria: February 21, 2024
• First Posted (Actual): February 28, 2024

Study Record Updates

• Last Update Posted (Actual): August 11, 2025
• Last Update Submitted That Met QC Criteria: August 6, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Postoperative Pain; Lower limb amputation; Phantom limb syndrome; Postoperative movilization
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Nervous System Diseases; Postoperative Complications; Pathologic Processes; Neurobehavioral Manifestations; Perceptual Disorders; Pain, Postoperative; Phantom Limb
• Other Study ID Numbers: 23-1036

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No