Clinical trial NCT04538417: C-RFA of Residual Limb Neuroma
Official title: Cooled Radiofrequency Ablation for the Treatment of Refractory Phantom and Residual Limb Pain; a Pilot Study.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Phantom Limb Pain
Neuroma Amputation
Keywords: Cooled Radiofrequency Ablation
Lead sponsor: University of Utah
Sponsor class: OTHER
First posted: 2020-09-04
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Participants who meet inclusion and exclusion criteria will be enrolled into the study after consenting to participate and before receiving residual limb neuroma C-RFA. This procedure is considered standard of care and are typically based on physician preference. Data will be collected by questionnaire at baseline and select follow up timelines.
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Age greater than 18 years of age at day of enrollment.
2. Clinical diagnosis lower extremity amputation performed more than 1 year since study enrollment.
3. Residual pain described as burning pain and sensations of movement in the affected amputated limb32.
4. Pain duration of more than 6 months despite a trial of conservative therapy (medications, physical therapy) for 2 months.
5. Ultrasound and / or MRI imaging pathology consistent with clinical symptoms and signs.
6. Greater than 50% pain relief with a diagnostic neuroma block

Exclusion Criteria:

1. Refusal or inability to participate, provide consent, or provide follow-up information for the 12-month duration of the study.
2. Contraindications to diagnostic block or treatment ablation (active infection, bleeding disorders, and pregnancy or breastfeeding, active immunosuppression, participation in another phantom or residual limb pain trial within the last 30 days
3. Non-neurogenic source of residual or phantom limb pain.
4. Active moderate to severe lumbar radiculopathy.
5. Any injection in the residual limb within the last 30 days.
6. Severe uncontrolled medical condition as determined by treating physician.
7. Severe psychological illness.
8. History of Inflammatory arthritis.
9. Malignancy within past 5 years except basal cell or squamous cell skin cancer. 10. Current opioid use exceeding50morphinemilligram equivalents per day.

11. A history of alcohol or drug abuse within past 5 years. 12. Use of any investigational drug within past 30 days. 13. Pending litigation involving participant's residual limb pain. 14. Incarceration

Primary outcomes:
measure: Numeric Rating Scale (NRS) for Pain at 6 Months
timeFrame: 6 months
Secondary outcomes:
measure: Median Change in Numeric Rating Scale (NRS) Scores for Pain
timeFrame: 1, 3, 6, and 12 months
measure: Medication Quantification Scale III Mean Score
timeFrame: 1, 3, 6 and 12 Months
measure: Proportion of Patients With a ≥6 Score on Patient Global Impression of Change (PGIC)
timeFrame: 1, 3, 6, and 12 months
Other outcomes:
Locations:
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
References: