A 17-Week Trial To Assess Pregabalin For The Treatment Of Nerve Pain Due To Spinal Cord Injury

Study Overview
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Brief Summary
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The purpose of this study is to evaluate if pregabalin relieves nerve pain associated with spinal cord injury compared to placebo (pill that contains no active medicine). This study will also evaluate the safety of pregabalin in this patient population.

Official Title
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A 17-Week, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multi-Center Trial Of Pregabalin For The Treatment Of Chronic Central Neuropathic Pain After Spinal Cord Injury

Conditions
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Neuralgia, Spinal Cord Injuries

Intervention / Treatment
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* Drug: placebo
* Drug: pregabalin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with nerve pain after Spinal cord injury (traumatic, diving, ischemic and after removal of benign tumors (except meningioma and fibromas) Pain has to be chronic(continuous for at least 3 months or intermittent for at least 6 months Pain score at least 4 in 4 of 7 days prior to receive treatment. Exclusion Criteria: Pregabalin use in the last 60 days, prior intolerance to pregabalin Creatinine clearance <60 mL/min. White blood cell count <2500/mm3; neutrophil count <1500/mm3; platelet count <100 x 103/ mm3. Abuse of drugs or alcohol Unstable medial conditions Clinically significant abnormal electrocardiogram (ECG). Presence of severe pain associated with conditions other than spinal cord injury that could confound the assessment or self-evaluation of pain due to spinal cord injury.

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 |
| --- | --- |
| Placebo Comparator: matched placebo<br> | Drug: placebo<br>* Placebo<br>|
| Experimental: pregabalin<br>flexible dosing over 4 weeks followed by 12 weeks maintenance and one week taper period | Drug: pregabalin<br>* Pregabalin capsules taken twice daily up to 17 weeks (150-600 mg/day)<br>* Other names: Lyrica;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration Adjusted Average Change (DAAC) of Mean Pain Score | DAAC was derived from participant's daily pain diary, where pain was measured on an 11-point Numerical Rating Scale (NRS-Pain)ranging from 0 (did not interfere with sleep) to 10 (completely interfered [unable to sleep due to pain]). The DAAC was calculated as the mean of all daily pain diary rating post baseline minus the baseline score then multiplied by the proportion of the planned study duration completed by the participant. | Baseline, Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Weekly Mean Pain Score | Mean weekly score was calculated as the average of the available daily diary pain score values for the week. Pain score was measured on an 11-point numeric rating scale (NRS): 0 (no pain) to 10 (worst possible pain). | Baseline, Week 16 | 
| Number of Participants With >=30% Reduction in Weekly Mean Pain Score From Baseline | Mean weekly score was calculated as the average of the available daily diary pain score values for the week. Pain score was measured on an 11-point numeric rating scale (NRS): 0 (no pain) to 10 (worst possible pain). | Baseline, Week 16 | 
| Number of Participants With Categorical Scores on the Patient Global Impression of Change (PGIC) (Full Scale) | The PGIC is a participant-rated instrument measuring change in the participant's overall status on a 7-point scale: 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, 7=very much worse. | Baseline, Week 16 | 
| Change From Baseline in Weekly Mean Sleep Interference Score | Pain-related sleep interference was assessed on an 11-point numerical rating scale ranging from 0 (did not interfere with sleep) to 10 (completely interfered [unable to sleep due to pain]). | Baseline, Week 16 | 
| Change From Baseline in Weekly Mean Pain Score by Week | Mean weekly score was calculated as the average of the available daily diary pain score values for the week. Pain score was measured on an 11-point numeric rating scale (NRS): 0 (no pain) to 10 (worst possible pain). | Baseline, Week 1 through16 | 
| Number of Participants With >=50% Reduction in Weekly Mean Pain Score From Baseline | Mean weekly score was calculated as the average of the available daily diary pain score values for the week. Pain score was measured on an 11-point numeric rating scale (NRS): 0 (no pain) to 10 (worst possible pain). | Baseline, Week 16 | 
| Change From Baseline in Modified Brief Pain Inventory Interference Scale (10-Item) (mBPI-10) Total Score | The Modified Brief Pain Inventory (mBPI-10) Interference Scale is a self administered questionnaire that assessed pain interference with functional activities over the past week. The items were measured on an 11 point scale, ranging from does not interfere (0) to completely interferes (10). A composite score, the pain interference index, was calculated by averaging the 10 items that comprised the scale. | Baseline, Week 16 | 
| Change From Baseline in Quantitative Assessment of Neuropathic Pain (QANeP) - Static Mechanical Allodynia | Participant rated pain scale. The pain produced by the applied stimulus (static mechanical allodynia - gentle constant mechanical pressure) was rated on an 11 point numerical rating scale (0=no pain, 10=worst possible pain). | Baseline, Week 16 | 
| Change From Baseline in Quantitative Assessment of Neuropathic Pain (QANeP) - Dynamic Mechanical Allodynia | Participant rated pain scale. The pain produced by the applied stimulus (dynamic mechanical allodynia - gentle stroking with foam brush) was rated on an 11 point numerical rating scale (0=no pain, 10=worst possible pain). | Baseline, Week 16 | 
| Change From Baseline in Quantitative Assessment of Neuropathic Pain (QANeP)- Punctata Hyperalgesia | Participant rated pain scale. The pain produced by the applied stimulus (Punctata hyperalgesia - pinprick) was rated on an 11 point numerical rating scale (0=no pain, 10=worst possible pain). | Baseline, Week 16 | 
| Change From Baseline in Quantitative Assessment of Neuropathic Pain (QANeP)- Temporal Summation to Tactile Stimuli | Participant rated pain scale. The pain produced by the applied stimulus (Temporal summation to tactile stimuli - repeated touching/tapping) was rated on an 11 point numerical rating scale (0=no pain, 10=worst possible pain). | Baseline, Week 16 | 
| Change From Baseline in Quantitative Assessment of Neuropathic Pain (QANeP)- Cold Allodynia | Participant rated pain scale. The pain produced by the applied stimulus (Cold allodynia - touch with cool metal rod 13-17 degrees celsius was rated on an 11 point numerical rating scale (0=no pain, 10=worst possible pain). | Baseline, Week 16 | 
| Change From Baseline in Quantitative Assessment of Neuropathic Pain (QANeP)- Cold Hyperalgesia Subscales | Participant rated pain scale. The pain produced by the applied stimulus (Cold hyperalgesia - touch with cold metal rod 4 degrees celsius) was rated on an 11 point numerical rating scale (0=no pain, 10=worst possible pain). | Baseline, Week 16 | 
| Change From Baseline in Neuropathic Pain Symptom Inventory (NPSI) - 12 Items Total Intensity Score | Participant rated questionnaire used 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 of 0-100. Higher score indicates a greater intensity of pain. | Baseline, Week 16 | 
| Change From Baseline in Neuropathic Pain Symptom Inventory (NPSI) - Burning Spontaneous Pain | Participant rated questionnaire used 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 of 0-100. Higher score indicates a greater intensity of pain. | Baseline, Week 16 | 
| Change From Baseline in Neuropathic Pain Symptom Inventory (NPSI) - Pressing Spontaneous Pain | Participant rated questionnaire used 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 of 0-100. Higher score indicates a greater intensity of pain. | Baseline, Week 16 | 
| Change From Baseline in Neuropathic Pain Symptom Inventory (NPSI) - Paroxysmal Pain | Participant rated questionnaire used 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 of 0-100. Higher score indicates a greater intensity of pain. | Baseline, Week 16 | 
| Change From Baseline in Neuropathic Pain Symptom Inventory (NPSI) - Evoked Pain | Participant rated questionnaire used 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 of 0-100. Higher score indicates a greater intensity of pain. | Baseline, Week 16 | 
| Change From Baseline in Neuropathic Pain Symptom Inventory (NPSI) - Paresthesia/Dysesthesia | Participant rated questionnaire used 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 of 0-100. Higher score indicates a greater intensity of pain. | Baseline, Week 16 | 
| Change From Baseline in Neuropathic Pain Symptom Inventory (NPSI) - Individual Item (1, 2, 3, 5, 6, 8, 9, 10, 11, 12) Score | Participant rated questionnaire used 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 of 0-100. Higher score indicates a greater intensity of pain. | Baseline, Week 16 | 
| Number of Participants With Improved Duration of Brief Pain Attacks Based on NPSI - Duration (Item 4) | NPSI - Temporal item which assesses the duration (number of hours during the last 24 hours) of spontaneous ongoing pain. Improved duration would be a decrease in the number of hours of spontaneous ongoing pain during the last 24 hours compared to baseline. | Baseline, Week 16 | 
| Number of Participants With Improvement in the Number of Attacks Based on NPSI - Number of Attacks (Item 7) | NPSI - Temporal item which assesses the paroxysmal pain (number of pain attacks during the last 24 hours). Improvement in the number of attacks would be a decrease in the number of paroxysms during the last 24 hours compared to baseline. | Baseline, Week 16 | 
| Change From Baseline in Medical Outcomes Study Sleep Scale (MOS-SS)- 9-Item Overall Sleep Problems Index | Participant 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. | Baseline, Week 16 | 
| Change From Baseline in Medical Outcomes Study Sleep Scale (MOS-SS) - Sleep Disturbance | Participant 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. | Baseline, Week 16 | 
| Change From Baseline in Medical Outcomes Study Sleep Scale (MOS-SS) - Sleep Adequacy | Participant 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. | Baseline, Week 16 | 
| Change From Baseline in Medical Outcomes Study Sleep Scale (MOS-SS) - Snoring | Participant 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. | Baseline, Week 16 | 
| Change From Baseline in Medical Outcomes Study Sleep Scale (MOS-SS) - Awaken Short of Breath or With a Headache | Participant 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. | Baseline, Week 16 | 
| Change From Baseline in Medical Outcomes Study Sleep Scale (MOS-SS) - Sleep Quantity | Participant 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. | Baseline, Week 16 | 
| Change From Baseline in Medical Outcomes Study Sleep Scale (MOS-SS) - Somnolence | Participant 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. | Baseline, Week 16 | 
| Number of Participants Having Optimal Sleep Based on Medical Outcomes Study Sleep Scale (MOS-SS) | Participant 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. | Baseline, Week 16 | 
| Change From Baseline in Hospital and Anxiety Depression Scale (HADS) - Anxiety | HADS: participant 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. | Baseline, Week 16 | 
| Change From Baseline in Hospital and Anxiety Depression Scale (HADS) - Depression | HADS: participant 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. | Baseline, Week 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pain, central neuropathic pain