A Trial of Lidocaine Patch for Lower Limb Amputation Pain

Study Overview
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Brief Summary
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Phantom limb pain (PLP) and scar hyperalgesia (SH) are frequent problems after amputation; in particular most persons who undergo limb amputation will experience phantom pain. The neuropathic nature of PLP suggests the involvement of both peripheral and central neurological mechanisms, including neuroplastic changes in the central nervous system. PLP as other central nervous system-related pain syndromes remains a challenge for treatment. Scar hyperalgesia involves peripheral mechanisms and results frim the production of substances liberated by damaged skin cells. These inflammatory substances lower the pain threshold by altering the chemical environment of skin nerve endings. Scan hyperalgesia is associated with secondary mechanical hyperalgesia in the skin area around the scar. The lidocaine patch 5% is a topical analgesic acting by blocking sodium channels of peripheral nerve endings and by inhibiting ectopic discharges in sensitized and hyperactive cutaneous nociceptors. The patch is noninvasive, with minimal systemic absorption resulting in a reduced risk of drug-drug interaction. In addition, a central analgesic effect of lidocaine has been suggested. The lidocaine patch 5% is currently licensed for the treatment of symptomatic postherpetic neuralgia. It also has been successfully used in patients with other neuropathic pain states, such as entrapment neuropathies, painful idiopathic distal sensory polyneuropathies and postoperative/post traumatic neuropathic chronic cutaneous pain. The lidocaine patch has not been studied for the management and prevention of phantom limb pain. The aim of the present research is to investigate if a lidocaine patch 5% is effective for reducing PLP and primary/secondary scar hyperalgesia. The hypothesis is that persistent peripheral nociceptive input from the stump after surgery may drive maladaptive cortical reorganization leading to chronic central pain and thus promote chronic phantom limb pain. Treating scar hyperalgesia on the stump with topical lidocaine may reduce the activity of peripheral nociceptive afferents and thus decrease the likelihood of developing persistent phantom limb pain. This study is designed as a randomized controlled multicentric double blind trial, in which the effectiveness of applying a 5% lidocaine patch for 6 weeks will be compared with a sham.

Official Title
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A Randomized Controlled Trial of Lidocaine Patch for Lower Limb Amputation Pain

Conditions
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Phantom Limb Pain (PLP), Primary/Secondary Scar Hyperalgesia

Intervention / Treatment
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* Drug: Lidocaine
* Other: Sham


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All above or below knee amputations , two months or more after surgery, after complete wound healing (no clips, no stitches, no seepage) Exclusion Criteria: History of central nervous system disease History of major psychiatric disease (MMS<23/30, HADS>8/21) Pregnancy Known hypersensitivity to local anesthetics (lidocaine, bupivacaine, etidocaine, mepivacaine, prilocaine) skin irritation on the stump

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lidocaine<br>During a period of six weeks, a lidocaine patch will be applied around the wound (cut in two parts, 1cm above and below the wound, without direct contact with the scar) for a total of twelve hours per day, during night time. | Drug: Lidocaine<br> <br> |
| Sham Comparator: Sham<br>During a period of six weeks, a visually identical patch (sham) will be applied around the wound (cut in two parts, 1cm above and below the wound, without direct contact with the scar) for a total of twelve hours per day, during night time. | Other: Sham<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient-reported overall daily pain intensity | The overall daily pain intensity (stump, scar and phantom pain combined) will be rated on a 0 to 100 visual analogue scale with anchors of 0 (no pain) to 100 (worst pain ever experienced). | Daily, starting seven days before patch placement (baseline) till six weeks after patch placement | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neuropathic Pain (DN4) | Screening for neuropathic pain, by using the DN4 questionnaire | at baseline - 7 days before patch placement | 
| Neuropathic pain | Rated with the Neuropathic Pain Symptom Inventory | at baseline - 7 days before patch placement | 
| Neuropathic pain | Rated with the Neuropathic Pain Symptom Inventory | One day after patch placement | 
| Neuropathic pain | Rated with the Neuropathic Pain Symptom Inventory | 6 weeks after patch placement | 
| Neuropathic pain | Rated with the Neuropathic Pain Symptom Inventory | 6 months after patch placement | 
| Pain (McGill) | Rated by the Short-Form McGill Pain Questionnaire, sensitive to the effects of pain treatment. | at baseline - 7 days before patch placement | 
| Pain (McGill) | Rated by the Short-Form McGill Pain Questionnaire, sensitive to the effects of pain treatment. | One day after patch placement | 
| Pain (McGill) | Rated by the Short-Form McGill Pain Questionnaire, sensitive to the effects of pain treatment. | 6 weeks after patch placement | 
| Quality of life | Rated by the SF36 questionnaire | at baseline -7 days before patch placement | 
| Quality of life | Will be rated by the SF36 questionnaire | six weeks after patch placement | 
| Quality of life | Will be rated by the SF36 questionnaire | six months after patch placement | 
| Sleep quality | will be assessed with the Pittsburgh Sleep Quality index | baseline -7 days before patch placement | 
| Sleep quality | will be assessed with the Pittsburgh Sleep Quality index | 6 weeks after patch placement | 
| Sleep quality | will be assessed with the Pittsburgh Sleep Quality index | 6 months after patch placement | 
| Delay of dress of provisory prosthesis | Number of days between surgery and delivery of temporary prosthesis | From the day of the surgery till the day of the delivery of temporary prosthesis, for a maximum of 6 months | 
| Delay of dress of provisory prosthesis | Number of days between inclusion in the research protocol and delivery of temporary prosthesis | From the day of patient inclusion in the research protocol till the day of the delivery of temporary prosthesis, for a maximum of 6 months | 
| Cumulative analgesic consumption (morphine equivalents) | Rated by the cumulative analgesic consumption score (CACS) | baseline -7 days before patch placement | 
| Cumulative analgesic consumption (morphine equivalents) | Rated by the cumulative analgesic consumption score (CACS) | 1 day after patch placement | 
| Cumulative analgesic consumption (morphine equivalents) | Rated by the cumulative analgesic consumption score (CACS) | 6 weeks after patch placement | 
| Phantom Limb Pain occurence | occurence of phantom limb pain | 6 months after patch placement | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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lidocaine, phantom limb pain (PLP), Primary/secondary scar hyperalgesia