Trial of Analgesia With Lidocaine or Extended-release Oxycodone for Neuropathic Pain Treatment in Multiple Sclerosis

Study Overview
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Brief Summary
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This study will determine whether treatment with an extended-release opioid or topical lidocaine is effective in relieving distal symmetric lower extremity burning pain associated with multiple sclerosis (MS). If treatment with topical lidocaine is efficacious, it will have important implications for understanding this chronic pain syndrome, which is widely assumed to be caused by central nervous system pathology.

Detailed Description
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This study is a single-center, double-blind, 15-week, 3-period crossover clinical trial. Subjects will complete each of the following 5-week long periods (unless they withdraw from the trial): 1) placebo pills and topical lidocaine patches, 2)extended-release oxycodone pills and placebo(vehicle) patches, and 3)placebo pills and placebo patches. Sixty subjects will be randomized to one of 6 treatment sequences. It is expected that this trial will take approximately 2 years to complete.

Official Title
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Trial of Analgesia With Lidocaine or Extended-release Oxycodone for Neuropathic Pain Treatment in Multiple Sclerosis (TALENT-MS)

Conditions
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Neuropathic Pain, Chronic Pain, Multiple Sclerosis

Intervention / Treatment
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* Drug: Lidocaine patch 5%
* Drug: Extended-release oxycodone
* Drug: Placebo extended-release oxycodone pills
* Drug: Placebo lidocaine patches


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Definite MS as defined by revised McDonald criteria. Bilateral distal symmetric burning pain involving both feet for at least three months. Baseline weekly average pain rating equal to four or greater on 0-10 numerical scale. Stable MS medication and pain-related medications for 8 weeks prior to screening. Must come to Research Center for appointments Exclusion Criteria: Topical treatment with lidocaine, capsaicin, or other topical analgesics within 3 months prior to screening. Any treatment with opioid analgesics or tramadol within 3 months prior to screening. Hypersensitivity to Lidoderm, lidocaine, or other local anesthetics. Hypersensitivity or inability to tolerate opioid analgesics. Current treatment with a total of 3 or more antidepressant or anticonvulsant drugs for pain. Current treatment with Class I anti-arrhythmic agents at baseline. Beck Depression Inventory score > 16 or clinically significant depression or dementia. History of suicide attempt or current intent or plan. History of excessive alcohol use or any illicit drug use within the past 2 years. Lack of adequate birth control in pre-menopausal women of childbearing age. Other pain more severe than lower extremity burning pain. Open skin lesions in the area where the lidocaine patch is to be applied. Cancer within the previous 5 years other than skin cancer. MS exacerbation or any treatment with corticosteroids within 3 months prior to screening. History of peripheral neuropathy, lower limb amputation, or another neuromuscular syndrome or systemic disorder known to be associated with sensory neuropathy. Does not meet criteria of baseline lab values at screening visit. Nerve conduction studies consistent with peripheral neuropathy.

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: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Lidocaine 5% + placebo patch, ER and placebo pills<br>5% lidocaine patch used as intervention placebo patch used with extended release oxycodone or with placebo pills and placebo patches a randomized subjects given extended release oxycodone and placebo patches during this treatment placebo pills used with lidocaine 5% patch group and with placebo patch/placebo pill group period | Drug: Lidocaine patch 5%<br>* lidocaine 5% patch; 12 hours on, 12 hours off<br>* Other names: Lidoderm;Drug: Extended-release oxycodone<br>* extended-release oxycodone titrating schedule<br>* Other names: Oxycontin;Drug: Placebo extended-release oxycodone pills<br>* placebo pills with titrating schedule<br>* Other names: Placebo pill;Drug: Placebo lidocaine patches<br>* used with extended release oxycodone group; used with placebo pills/placebo patches<br>* Other names: Placebo patch;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Daily Diary Pain Ratings During Final Week of Each Treatment Period | subject identifies daily pain rating during final week of each treatment period using a numeric rating scale | Daily | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tolerability (e.g., Number of Adverse Effects, Number of Drop-outs) | subject is questioned regarding any adverse events that have occured since the last contact; also subject can document any issues on daily pain rating diaries | rating of adverse events occur at each visit | 
| Safety (i.e., Number of Serious Adverse Events) | Subject is asked about any adverse events that may have occurred since last contact; also subject can document any adverse events on daily pain diary scales | rating and review of any adverse events occurs at each visit | 
| Brief Pain Inventory Interference Items | subject completes the brief pain questionaire | occurs Visit 1, 3,4,5 | 
| Daily Diary Sleep Interference Ratings | Subject identifies degree of sleep interference on a daily basis | daily | 
| Beck Depression Inventory | Subject completes Beck questionaire | occurs at Visit 1, 3, 4 and 5 | 
| Short-form Health Survey 36 (SF-36) | Subject completes short form health survey 36 questionaire | Occurs at Visit 1, 3, 4 and 5 | 
| Short-Form McGill Pain Questionnaire | Subject completes short form McGill Pain questionaire | Occurs Visit 1, 3, 4 and 5 | 
| Patient Global Impression of Change Scale | Subject completes patient global impression questionaire of change scale | Occurs Visit 3, 4, 5 | 
| Kurtzke Expanded Disability Status Scale | Subject completes questionaire on functional status | Occurs at Visit 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neuropathic pain, Chronic pain, Multiple sclerosis, Central neuropathic pain, Peripheral neuropathic pain, Opioid analgesic, Lidocaine