Neuropathic Pain, Chronic Pain, Multiple Sclerosis
Conditions
Keywords
Neuropathic pain, Chronic pain, Multiple sclerosis, Central neuropathic pain, Peripheral neuropathic pain, Opioid analgesic, Lidocaine
Brief summary
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
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.
Interventions
lidocaine 5% patch; 12 hours on, 12 hours off
extended-release oxycodone titrating schedule
DRUGPlacebo extended-release oxycodone pills
placebo pills with titrating schedule
DRUGPlacebo lidocaine patches
used with extended release oxycodone group; used with placebo pills/placebo patches
Sponsors
Endo Pharmaceuticals
University of Rochester
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Daily Diary Pain Ratings During Final Week of Each Treatment Period | Daily | subject identifies daily pain rating during final week of each treatment period using a numeric rating scale |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety (i.e., Number of Serious Adverse Events) | rating and review of any adverse events occurs at each visit | 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 |
| Brief Pain Inventory Interference Items | occurs Visit 1, 3,4,5 | subject completes the brief pain questionaire |
| Daily Diary Sleep Interference Ratings | daily | Subject identifies degree of sleep interference on a daily basis |
| Beck Depression Inventory | occurs at Visit 1, 3, 4 and 5 | Subject completes Beck questionaire |
| Tolerability (e.g., Number of Adverse Effects, Number of Drop-outs) | rating of adverse events occur at each visit | 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 |
| Short-Form McGill Pain Questionnaire | Occurs Visit 1, 3, 4 and 5 | Subject completes short form McGill Pain questionaire |
| Patient Global Impression of Change Scale | Occurs Visit 3, 4, 5 | Subject completes patient global impression questionaire of change scale |
| Kurtzke Expanded Disability Status Scale | Occurs at Visit 1 | Subject completes questionaire on functional status |
| Short-form Health Survey 36 (SF-36) | Occurs at Visit 1, 3, 4 and 5 | Subject completes short form health survey 36 questionaire |
Countries
United States
Participant flow
Recruitment details
7-6-2006 to 9-23-2008 at the medical center
Pre-assignment details
19 subjects were enrolled in this study however the study was terminated due to not reaching enrollment goals in a timely manner. Therefore there was no data analysis completed for this study. We do not have randomization data for these participants because the data is not available and is locked.
Participants by arm
| Arm | Count |
|---|---|
| Lidocaine 5% + Placebo Patch, ER + Placebo Pills 5% lidocaine patch used as intervention Lidocaine patch 5%: lidocaine 5% patch; 12 hours on, 12 hours off
placebo patch used with extended release oxycodone or with placebo pills and placebo patches arm Placebo lidocaine patches: used with extended release oxycodone group; used with placebo prandomized subjects given extended release oxycodone and placebo patches during this treatment period
Extended-release oxycodone: extended-release oxycodone titrating scheduleills/placebo patches
placebo pills used with lidocaine 5% patch group and with placebo patch/placebo pill group
Placebo extended-release oxycodone pills: placebo pills with titrating schedule | 19 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Abnormal lab work | 16 |
Baseline characteristics
| Characteristic | Lidocaine 5% + Placebo Patch, ER + Placebo Pills |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants |
| Region of Enrollment United States | 19 participants |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
Outcome results
Primary
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
Time frame: Daily
Population: Data was not analyzed because we the data is locked and is not available.
Secondary
Beck Depression Inventory
Subject completes Beck questionaire
Time frame: occurs at Visit 1, 3, 4 and 5
Population: Data was not analyzed because we did not reach our enrollment goal and the study was terminated. Data was not analyzed because we the data is locked and is not available.
Secondary
Brief Pain Inventory Interference Items
subject completes the brief pain questionaire
Time frame: occurs Visit 1, 3,4,5
Population: Data was not analyzed because we did not reach our enrollment goal and the study was terminated. Data was not analyzed because we the data is locked and is not available.
Secondary
Daily Diary Sleep Interference Ratings
Subject identifies degree of sleep interference on a daily basis
Time frame: daily
Population: Data was not analyzed because we did not reach our enrollment goal and the study was terminated.. Data was not analyzed because we the data is locked and is not available.
Secondary
Kurtzke Expanded Disability Status Scale
Subject completes questionaire on functional status
Time frame: Occurs at Visit 1
Population: Data was not analyzed because we did not reach our enrollment goal and the study was terminated. Data was not analyzed because we the data is locked and is not available.
Secondary
Patient Global Impression of Change Scale
Subject completes patient global impression questionaire of change scale
Time frame: Occurs Visit 3, 4, 5
Population: Data was not analyzed because we did not reach our enrollment goal and the study was terminated. Data was not analyzed because we the data is locked and is not available.
Secondary
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
Time frame: rating and review of any adverse events occurs at each visit
Population: Data was not analyzed because we did not reach our enrollment goal and the study was terminated. Data was not analyzed because we the data is locked and is not available.
Secondary
Short-form Health Survey 36 (SF-36)
Subject completes short form health survey 36 questionaire
Time frame: Occurs at Visit 1, 3, 4 and 5
Population: Data was not analyzed because we did not reach our enrollment goal and the study was terminated. Data was not analyzed because we the data is locked and is not available.
Secondary
Short-Form McGill Pain Questionnaire
Subject completes short form McGill Pain questionaire
Time frame: Occurs Visit 1, 3, 4 and 5
Population: Data was not analyzed because we did not reach our enrollment goal and the study was terminated. Data was not analyzed because we the data is locked and is not available.
Secondary
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
Time frame: rating of adverse events occur at each visit
Population: Data was not analyzed because we did not reach our enrollment goal and the study was terminated. Data was not analyzed because we the data is locked and is not available.