An interventional study of Cooled Radiofrequency Ablation in Phantom Limb Pain and Neuroma Amputation, sponsored by University of Utah. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-01-08.
Sponsored by University of Utah · Not applicable, Interventional, and Treatment
To assess changes in pain, physical function, and health-related quality of life in patients with post-amputation neuroma-associated residual limb pain after cooled radiofrequency ablation.
Residual limb (RLP) and phantom limb pain (PLP) affects most amputees at some point in their life1. The incidence of PLP has been estimated to range between 50 - 80%. RLP prevalence has been estimated to be 43%. The peak of onset is bimodal and often appears within the first month and second year after amputation. RLP is more common in the first year after amputation, with PLP becoming the predominate amputee pain complaint after one-year post-amputation.
Both RLP and PLP fall under the umbrella term "post-amputation pain." While these conditions are frequently found in combination, their clinical features and underlying causes are distinct. PLP is a painful sensation in the distribution of the missing limb. Following amputation, abnormalities at multiple levels of the neural axis have been implicated in the development of PLP; changes include cortical reorganization, reduced inhibitory processes at the spinal cord, synaptic response changes and hyperexcitability at the dorsal root ganglion, and retrograde peripheral nerves shrinkage.
Residual limb pain has been called "neuroma pain" and is mechanistically distinct from PLP11. Neuromas may form as early 6-10 weeks after nerve transection, and are thought the produce ectopic neural discharges resulting in severe pain. Evidence suggests RLP and PLP commonly co-occur and patients may struggle to differentiate between these pain types. Risk factors include female sex, upper extremity amputation, pre-amputation pain, residual pain in contralateral limb, and time since amputation.
Depression, anxiety, and stress are known to exacerbate PLP / RLP. Patients experiencing PLP and RLP also experience a higher incidence of indecisiveness, suicidal ideation, and thoughts of self-harm8. Current guidelines for treatment of PLP and RLP are not standardized. Treatments includes pre-operative analgesia, neuromodulation mirror therapy, imagery, acupuncture, transcranial stimulation, deep brain stimulation, and medications (including, but not limited to: TCAs, SSRIs, gabapentinoids, sodium channel blockers, ketamine, opioids, and NSAIDs). Many agents have been injected in neuromas. These include local anesthetic, phenol, alcohol, and botulinum toxin. These oral, intravenous, and nonpharmacological modalities have demonstrated limited success in the treatment of PLP / RLP. Neuroma cryoablation has been used, but this method of neural destruction poses technical challenges related to cumbersome needle placement and the requirement for time-intensive freeze-thaw cycles.
Conventional RFA has been studied on RLP. Zhang et. al treated 13 patients with painful stump neuromas. The study started with alcohol neurolysis before using ultrasound-guided RFA for refractory cases. The frequency of sharp pain was reduced in all RFA-treated patients. Kim et. al described a case in which ultrasound-guided RFA was successfully used to treat a sciatic neuroma of an above-knee amputee.
No outcome literature on the effectiveness of C-RFA technology has been published. C-RFA is similar in mechanism to conventional RFA: a thermal lesion is created by applying radiofrequency energy through an electrode placed at a target structure. In C-RFA, a constant flow of ambient water is circulated through the electrode via a peristaltic pump, maintaining a lowered tissue temperature by creating a heat sink. By removing heat from tissues immediately adjacent to the electrode tip, a lower lesioning temperature is maintained, resulting in less tissue charring adjacent to the electrode, less tissue impedance and more efficient heating of target tissue. The volume of tissue heated, and the resultant thermal lesion size is substantially larger with C-RFA, conferring an advantage over conventional RFA. Further, given the spherical geometry and forward projection the C-RFA lesions beyond the distal end of the electrode, the RFA probe can be positioned at a range of possible angles and still capture the target neural structure, whereas more fastidious, parallel positioning is required with conventional RFA. These technical advantages increase the probability of successful denervation of neural pain generators that have variability in anatomic location. Additionally, a longer lesion of the RLP-generating nerve may be more reliably achieved with C-RFA compared to conventional RFA.
As such, the present study aims to define the attributable effect of cooled RFA on pain, physical function, and health-related quality of life in patients with post-amputation neuroma-associated residual limb pain. This prospective single-arm pilot study is intended to inform a future properly powered randomized controlled trial.
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This study's enrollment of 8 is below the median of 33 across 49 interventional studies indexed under Neuroma.
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Exclusion Criteria:
Patient has residual limb pain in amputated limb and is scheduled to receive standard of care treatment of cooled radiofrequency ablation.
Device: Cooled Radiofrequency Ablation
RFA procedures will be performed with modification accounting for appropriate C-RFA technique. Participant will be positioned prone and skin prepped with chloroprep. Ultrasound probe will be placed on residual limb at a transverse angle in order to view the nerve and associated neuroma in long-axis. The probe will be advanced to the site of the stump neuroma. C-RFA electrode will be placed adjacent to neuroma. Needle will be connected via wire to a cooled radiofrequency generator. Motor and sensory testing will be performed to reproduce or exacerbate the RLP and / or PLP. At the site of the neuroma, 2 mL of local anesthetic will be injected through the needle. C-RFA lesions will be created by using the typical C-RFA protocol. Upon completion needle will be removed. Following ablation, 0.5 mL of 0.5% bupivacaine will be injected at the site of the ablated neuroma to provide post procedure analgesia.
Numeric Rating Scale (NRS) for Pain at 6 Months
Presented here is the proportion of participants reporting ≥50% improvement in Numeric Rating Scale pain score at 6 months after their cooled radiofrequency ablation procedure. The Numeric Rating Scale was used to quantify neuroma-associated residual limb pain by asking patients to rate their pain intensity on an 11-point scale ranging from 0 to 10, with 0 representing "no pain at all" and 10 representing "the worst pain imaginable".
Time frame: 6 months
Median Change in Numeric Rating Scale (NRS) Scores for Pain
Patients rated their residual limb pain intensity at baseline and the designated follow-up timepoints using an 11-point Numeric Rating Scale (NRS) ranging from 0 to 10, with 0 representing "no pain at all" and 10 representing "the worst pain imaginable". Change scores were calculated by subtracting follow-up scores from baseline scores. Median change scores and their interquartile ranges are reported here. Positive median change scores indicate pain improvement from baseline, with greater values corresponding to greater pain relief. Similarly, negative change scores indicate worsening pain from baseline.
Time frame: 1, 3, 6, and 12 months
Medication Quantification Scale III Mean Score
The Medication Quantification Scale (MQS) is calculated using a pain-related medication detriment score based on drug class, which ranges from 1.1 to 4.5, and multiplying it by a usage score: 1 = subtherapeutic or occasional dose/2 = lower 50% of a therapeutic dose/ 3 = upper 50% of a therapeutic dose/ 4 = supratherapeutic dose. The higher the score, the more pain-related medication the participant takes to control their pain. The resulting score is useful in research for tracking individual or group pain medication use over time.
Time frame: 1, 3, 6 and 12 Months
Proportion of Patients With a ≥6 Score on Patient Global Impression of Change (PGIC)
Patient Global Impression of Change is a scale which measures participant reported satisfaction after an intervention. The outcome was measured as the percent of patients reporting a PGIC score of 6-7 (indicating "much improved" and "very much improved").
Time frame: 1, 3, 6, and 12 months
| Milestone | Residual Limb Pain in Affected Amputated Limb |
|---|---|
| Started | 8 |
| Withdrew to have phenol ablation | 1 |
| Withdrew to have targeted muscle reinnervation therapy | 1 |
| Completed | 6 |
| Not completed | 2 |
| Withdrew: Withdrawal by subject | 2 |
Presented here is the proportion of participants reporting ≥50% improvement in Numeric Rating Scale pain score at 6 months after their cooled radiofrequency ablation procedure. The Numeric Rating Scale was used to quantify neuroma-associated residual limb pain by asking patients to rate their pain intensity on an 11-point scale ranging from 0 to 10, with 0 representing "no pain at all" and 10 representing "the worst pain imaginable".
| Participants | Residual Limb Pain in Affected Amputated Limb |
|---|---|
| Numeric Rating Scale (NRS) for Pain at 6 Months | 4 |
Patients rated their residual limb pain intensity at baseline and the designated follow-up timepoints using an 11-point Numeric Rating Scale (NRS) ranging from 0 to 10, with 0 representing "no pain at all" and 10 representing "the worst pain imaginable". Change scores were calculated by subtracting follow-up scores from baseline scores. Median change scores and their interquartile ranges are reported here. Positive median change scores indicate pain improvement from baseline, with greater values corresponding to greater pain relief. Similarly, negative change scores indicate worsening pain from baseline.
| units on a scale | Residual Limb Pain in Affected Amputated Limb |
|---|---|
| 1 month | 1.0 (0.5 to 3.0) |
| 3 months | 2.0 (1.5 to 2.5) |
| 6 months | 1.0 (-1.5 to 3.0) |
| 12 months | 3.0 (1.3 to 4.0) |
The Medication Quantification Scale (MQS) is calculated using a pain-related medication detriment score based on drug class, which ranges from 1.1 to 4.5, and multiplying it by a usage score: 1 = subtherapeutic or occasional dose/2 = lower 50% of a therapeutic dose/ 3 = upper 50% of a therapeutic dose/ 4 = supratherapeutic dose. The higher the score, the more pain-related medication the participant takes to control their pain. The resulting score is useful in research for tracking individual or group pain medication use over time.
| Score on a scale | Residual Limb Pain in Affected Amputated Limb |
|---|---|
| 1 Month | 8.3 (6.1 to 10.0) |
| 3 Months | 6.9 (4.6 to 8.1) |
| 6 Months | 7.1 (3.6 to 8.5) |
| 12 Months | 7.1 (2.4 to 9.7) |
Patient Global Impression of Change is a scale which measures participant reported satisfaction after an intervention. The outcome was measured as the percent of patients reporting a PGIC score of 6-7 (indicating "much improved" and "very much improved").
| Participants | Residual Limb Pain in Affected Amputated Limb |
|---|---|
| 1 month | 3 |
| 3 months | 3 |
| 6 months | 1 |
| 12 months | 1 |
Collected over The day of the procedure. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Residual Limb Pain in Affected Amputated Limb | 0/8 (0%) | 0/8 (0%) | 0/8 (0%) |
| Age, Categorical(Participants) | Residual Limb Pain in Affected Amputated Limb |
|---|---|
| <=18 years | 0 |
| Between 18 and 65 years | 4 |
| >=65 years | 3 |
| Age, Continuous(years) | Residual Limb Pain in Affected Amputated Limb |
|---|---|
| Mean | 60.3 (25 to 75) |
| Sex: Female, Male(Participants) | Residual Limb Pain in Affected Amputated Limb |
|---|---|
| Female | 1 |
| Male | 6 |
| Race and Ethnicity Not Collected(Participants) | Residual Limb Pain in Affected Amputated Limb |
|---|
| Region of Enrollment(participants) | Residual Limb Pain in Affected Amputated Limb |
|---|---|
| United States | 7 |
| Height(Centimeters) | Residual Limb Pain in Affected Amputated Limb |
|---|---|
| Mean | 166.2 ± 16.17 |
| Weight(Kilograms) | Residual Limb Pain in Affected Amputated Limb |
|---|---|
| Mean | 86.8 ± 19.17 |
| Duration of Pain(Participants) | Residual Limb Pain in Affected Amputated Limb |
|---|---|
| < 1 Year | 1 |
| 1 to 5 Years | 4 |
| > 5 Years | 2 |
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