Efficacy Of Pregabalin In Subjects With Post-Stroke Central Neuropathic Pain

Study Overview
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Brief Summary
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Efficacy and Safety of flexibly dosed pregabalin compared to placebo among subjects with central post stroke pain (CPSP)

Official Title
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A 13-Week, Randomized, Multi-Center, Double-Blind, Placebo-Controlled, Parallel-Group Study To Evaluate The Efficacy, Safety And Tolerability Of Pregabalin (150-600 Mg/Day) Using A Flexible Dosing Schedule In The Treatment Of Subjects With Central Post-Stroke Pain (CPSP)

Conditions
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Central Neuropathic Pain

Intervention / Treatment
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* Drug: Pregabalin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Positive history of clinical stroke at least 4 months prior to randomization CPSP--3 months prior to screening Exclusion Criteria: History of dementia or any other severe cognitive impairment Diabetic Peripheral Neuropathy (DPN)

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Pregabalin<br>The change from in pain scores from baseline to endpoint among stroke subjects receiving pregabalin will be compared to change in pain scores from baseline to endpoint among stroke subjects receiving matched placebo. | Drug: Pregabalin<br>* Eligible subjects with post-stroke central pain will be randomized to receive double blinded treatment using pregabalin or matched placebo. The effects of pregabalin as compared to placebo on pain pain symptoms will be compared over the 13 week clinical trial. At baseline following pain ratings and clinical measures, subjects randomized to pregabalin receive instructions to take 75mg twice a day for 7days. The dosing of pregabalin or matching placebo will be titrated over the first 4 weeks (based on tolerability and pain scores). (Range 150-600mg) After the 4th week, the dose of medication will be maintained until week 12 (when tapering of medication begins) Ratings of Pain severity, review of pain/sleep diaries as well as medication tolerance occur bi-weekly throughout the study. Tapering off med occurs from week 12-13.<br>|
| Placebo Comparator: Placebo<br>The change in pain scores from baseline to endpoint will be compared among the two treatment groups- ie subjects receiving 12 weeks of pregabalin treatment vs subjects receiving 12 weeks of placebo treatment. | Drug: Placebo<br>* Eligible subjects with post-stroke central pain will be randomized to receive double blinded treatment using pregabalin or matched placebo. The effects of pregabalin as compared to placebo on pain pain symptoms will be compared over the 13 week clinical trial. At baseline following pain ratings and clinical measures, subjects randomized to pregabalin receive instructions to take 75mg twice a day for 7days. The dosing of pregabalin or matching placebo will be titrated over the first 4 weeks (based on tolerability and pain scores). (Range 150-600mg) After the 4th week, the dose of medication will be maintained until week 12 (when tapering of medication begins) Ratings of Pain severity, review of pain/sleep diaries as well as medication tolerance occur bi-weekly throughout the study. Tapering off med occurs from week 12-13.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Pain Score at Endpoint as Measured by Daily Pain Rating Scale (DPRS) | Mean pain score obtained from last 7 available DPRS scores up to and including day of Week 12 visit or early termination (ET) equivalent. DPRS: subject rated 11-point numeric scale ranging from 0 (no pain) to 10 (worst possible pain) during past 24-hour period. Higher score indicates greater level of pain. Self-assessment performed daily on awakening prior to taking study medication. | Up to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Score as Measured by DPRS | Weekly mean pain score measured by DPRS: subject rated 11-point numeric scale ranging from 0 (no pain) to 10 (worst possible pain) during past 24-hour period. Higher score indicates greater level of pain. Self-assessment performed daily on awakening prior to taking study medication. | Week 1, Week 2, Week 3, Week 6, Week 9, and Week 12 | 
| Number of Subjects With at Least a 30% Reduction From Baseline in Mean Pain Score at Endpoint | 30% Responder Yes = number of subjects with 30% reduction in mean pain score from baseline to observation; 30% reduction calculated as [(T minus B) divided by B multiplied by 100] < = negative 30. T = endpoint mean pain score (obtained from last 7 available scores from DPRS); B = baseline mean pain score (obtained from average of last 7 daily scores from DPRS). 30% Responder No indicates number of subjects that did not reach 30% reduction in mean pain score. | Baseline, Week 12 | 
| Number of Subjects With at Least a 50% Reduction From Baseline in Mean Pain Score at Endpoint | 50% Responder Yes = number of subjects with 50% reduction in mean pain score from baseline to observation; 50% reduction calculated as [(T minus B) divided by B multiplied by 100] < = negative 50. T = endpoint mean pain score (obtained from last 7 available scores from DPRS); B = baseline mean pain score (obtained from average of last 7 daily scores from DPRS). 50% Responder No indicates number of subjects that did not reach 50% reduction in mean pain score. | Baseline, Week 12 | 
| Weekly Mean Sleep Interference Score From Daily Sleep Diary (Daily Sleep Interference Scale [DSIS]) | DSIS: subject rated 11-point numeric scale ranging from 0 (pain does not interfere with sleep) to 10 (pain completely interferes with sleep) during past 24-hour period. Higher score indicates a greater level of sleep disturbance. Self-assessment performed daily on awakening prior to taking study medication. Endpoint calculated as mean of last 7 available scores. | Week 1, Week 2, Week 3, Week 6, Week 9, and Week 12 | 
| Short Form-McGill Pain Questionnaire (SF-MPQ Visual Analog Scale [VAS]) - Part B Only | SF-MPQ Part B VAS consists of a line 0 to 100 millimeters (mm) in length; range is (no pain) to 100 mm (worst possible pain). Subjects placed a mark indicating the intensity of their pain. Distance from left-hand end of line was measured and entered on Case Report Form (CRF) as score in mm. Higher score indicates greater level of pain. | Week 12 | 
| Neuropathic Pain Symptom Inventory (NPSI) | NPSI: subject rated questionnaire to evaluate different symptoms of neuropathic pain (dimensions: burning [superficial] spontaneous pain, pressing [deep] spontaneous pain, paroxysmal pain, evoked pain, and paresthesia/dyesthesia [P/D]). Includes 10 descriptors quantified on a 0 (no symptoms) to 10 (worst symptoms imaginable) and 2 temporal items assessing duration of spontaneous ongoing and paroxysmal pain. Questionnaire generates a score in each of the relevant dimensions and a total score (0 to 100). Higher score indicates a greater intensity of pain. | Week 12 | 
| Medical Outcome Study (MOS) Sleep Scale | MOS: subject rated questionnaire to assess sleep quality and quantity. Consists of a 9-item overall sleep problems index (length of time to fall asleep, how many hours of sleep each night during past 4 weeks); 7 subscales rated 1 (all the time) to 6 (none of the time): sleep disturbance, snoring, awaken short of breath (SOB) or with a headache, somnolence adequacy, and sleep quantity. Scores are transformed (actual raw score minus lowest possible score divided by possible raw score range multiplied by 100); total score range = 0 to 100; higher score indicates greater intensity of attribute. | Week 12 | 
| Number of Subjects With Yes or No Response for Medical Outcome Study (MOS) Sleep Scale - Optimal Sleep | MOS: subject rated questionnaire to assess sleep quality and quantity. Optimal sleep component is derived from Sleep Quantity average hours of sleep each night during the past 4 weeks. Number of subjects with response = YES if sleep quantity is 7 or 8 hours per night or response = NO if sleep quantity is < 7 hours per night. | Week 12 | 
| Hospital Anxiety and Depression Scale (HADS) - ITT Population | HADS is subject rated questionnaire with 2 subscales. HADS-A assesses state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks); HADS-D assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). Each subscale comprised of 7 items with range 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Total score 0 to 21 for each subscale; higher score indicates greater severity of anxiety and depression symptoms. | Week 12 | 
| Euro Quality of Life (EQ-5D)- Health State Profile Utility Score | EQ-5D: subject rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state (eg, confined to bed). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. | Week 12 | 
| EQ-5D - VAS | EQ-5D: subject rated questionnaire to assess health-related quality of life in terms of a single index value. The VAS component rates current health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better health state. | Week 12 | 
| Patient Global Impression of Change (PGIC) | PGIC: subject rated instrument to measure subject's change in overall status on a 7-point scale; range from 1 (very much improved) to 7 (very much worse). | Week 12 | 
| Clinical Global Impression of Change (CGIC) | CGIC: clinician rated instrument that measures change in a subject's ovall status on a 7-point scale; range from 1 (very much improved) to 7 (very much worse). | Week 12 | 
| Quantitative Assessment of Neuropathic Pain (QANeP) - Sensory Threshold | QANeP: assessment of sensory threshold: subject responds yes when monofilament stimulus is felt on area of maximum pain: 1 (lowest/softest 0.07 gram [g]) to 6 (highest 300 g) or 7 (not perceived); rated by lowest/softest filament felt when in contact with the skin. Summarized as change from baseline (mean at observation minus mean at baseline). | Baseline, Week 12 | 
| QANeP - Pain Rating Scales | Subject rated pain scale: static mechanical allodynia (SMA) gentle constant mechanical pressure; dynamic mechanical allodynia (DMA) gentle stroking with foam brush; punctate hyperalgesia (PH) pinprick; cold allodynia (CA) touch with cool metal rod 13-17° celsius (C); cold hyperalgesia (CH) touch with cold metal rod 4° C; temporal summation to tactile stimuli (TSTS) repeated touching/tapping. 11-point numeric scale; range 0 (no pain) to 10 (worst possible pain). Reference area=mirror image of pain site (test area). Summarized as change from baseline (mean at observation minus mean at baseline). | Baseline, Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Post-stroke pain, pregabalin