Study to Determine if a Reduction in Pain Can be Measured in Spinal Cord Injured Patients Using a New Study Design

Study Overview
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Brief Summary
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The study is designed to assess if spinal cord injury patients have reduced pain after taking either pregabalin or placebo in a cross over design. Patients had either pain at the level of their injury or below the level of their injury.

Detailed Description
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This methodology study was terminated on October 13, 2008 based on interim results for an exploratory, novel endpoint. The results of the primary analysis at the interim for N=12 patients showed results that generally favored pregabalin but were not statistically significant compared to placebo. Based on the estimated conditional power, this result is unlikely to change with full recruitment of N=24 patients and therefore the data monitoring committee recommended termination of the trial. The decision to terminate the trial was not based on any safety concerns.

Official Title
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A Methodology Study to Assess the Ability of a Randomised, Double Blind, Placebo Controlled, Crossover Trial Design in Spinal Cord Injury Patients With Pain of Neuropathic Origin to Detect Improvement in Pain Endpoints Using Pregabalin as a Benchmark Compound

Conditions
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Spinal Cord Injuries

Intervention / Treatment
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* Drug: Pregabalin
* Drug: Placebo for pregabalin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: subjects who are outpatients or inpatients written informed consent obtained (signed by the subject or the subject's legally acceptable representative) traumatic spinal cord injury of at least 1 year duration with a nonprogressive, i.e., chronic, stage of at least 6 months duration At-level neuropathic pain: spontaneous or evoked pain with neuropathic features (sharp, shooting, electric or burning pain sensation) in the region of sensory disturbance in a segmental pattern and located within two dermatomes above or below the level of spinal cord injury Below-level neuropathic pain: spontaneous or evoked pain with neuropathic features (sharp, shooting, electric or burning pain sensation) in the region of sensory disturbance located at least three dermatomes below the level of spinal cord injury Exclusion Criteria: spinal cord injury (subjects with central pain and musculoskeletal pain must be able to make a distinction between the two) subjects who have previously not responded to 300 mg/day pregabalin: a non-responder is defined as a subject who has a reduction in pain score of less than 30% from baseline

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pregabalin<br> | Drug: Pregabalin<br>* Pregabalin 150mg capsules BID for 7.5 days<br>|
| Other: Placebo<br> | Drug: Placebo for pregabalin<br>* Placebo capsules BID for 7.5 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Present Pain Intensity Score | Present pain intensity score: 0-10 numeric rating scale (NRS), 0 (no pain) to 10 (worst possible pain). | Day 1: 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours (post-dose); Day 8: 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours (post-dose) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Daily Pain Score | Daily Pain Score: Day 1 pain intensity over past 24 hours recorded on waking every morning. 0-10 numeric rating scale (NRS): 0 (no pain) to 10 (worst possible pain). | Predose: Daily from 7 days before Visit 2 (start of Intervention 1) until the morning of Visit 5 (end of Intervention 2) | 
| Dynamic Allodynia Area | Area of dynamic allodynia was assessed using a brush (SENSElab Brush 05; velocity approximately 20 millimeters per second [mm/s]) by stimulating along a pattern of 8 radial spokes. Stimulation was started from the non-painful perimetry. Subjects were asked to report change in sensation from non-painful to painful and the spot was marked onto the skin. The area of dynamic allodynia was determined from these 8 distances by calculating the area of an octagon (in centimeter squared [cm2]). | Screening, Days 1 & 8: 0 (pre-dose) & 4 hours post-dose, | 
| Dynamic Allodynia Pain Score | Five strokes (each approx. 6 centimeters [cm] long) were applied with a standardized brush (SENSELab Brush 05) across the painful site (and a control site) at a constant velocity (20 millimeters per second [mm/sec]). Pain in response to brush stimulation of the allodynic area was recorded using an 11-point numeric rating scale from 0 (no pain) to 10 (worst possible pain). Patients were asked to give a pain rating after each brush stroke. A painful sensation was considered as representing brush allodynia. | Screening, Days 1 & 8: 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, and 6 hours post-dose | 
| Punctate Allodynia Area | Area of punctate allodynia was determined using a von Frey filament (OptiHair2). Stimulation was started from the non-painful perimetry and repeated along a pattern of 8 radial spokes. With a movement along each spoke at steps of 5 millimeters (mm), the subjects reported sensation changes from non-painful to painful and the spot was marked on the skin. The area of punctate allodynia was determined from these 8 distances by calculating the area of an octagon (in square centimeter(s)[cm2]). | Screening, Days 1 & 8: 0 (pre-dose) and 4 hours post-dose | 
| Mechanical Pain Sensitivity Stimulus-Response Function | Mechanical pain sensitivity stimulus response function was assessed at the control and painful sites using calibrated von Frey monofilaments and the SENSElab brush. Seven different von Frey monofilaments (8 -512 milliNewtons [mN], force increases by a factor of two from filament to filament) and the brush were applied in a predetermined pseudo-random order. Pain rating for each stimulus: 11-point numeric rating scale (NRS) ranging from 0 (no pain) to 10 (worst possible pain). | Screening, Days 1 & 8: 0 (pre-dose), & 2, 4, and 6 hours post-dose | 
| Neuropathic Pain Symptom Inventory (NPSI) | NPSI: subject rated questionnaire to evaluate 5 dimensions of neuropathic pain (dimensions: burning [superficial] spontaneous pain, pressing [deep] spontaneous pain, paroxysmal pain, evoked pain, and paresthesia/dyesthesia). Includes 10 descriptors ranging from 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 relevant dimension. Total score is calculated as the sum of scores of the 10 descriptors, range: 0-100. Higher score indicates greater intensity of pain. | Prior to morning dosing on Day 1 and prior to discharge on Day 8 for each period. | 
| Pharmacokinetic Evaluations of Pregabalin | Pharmacokinetic (PK) results are not presented in this report due to early termination of the trial. Pregabalin PK was not measured as there was incomplete data to conduct pharmacokinetic/pharmacodynamic analyses. | Day 1: 0 (pre-dose), 0.5, 1, 2, and 6 hours post-dose; Day 8: 0 (pre-dose), 1, 4, & 6 hours post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Clinical Trial Methodology study Neuropathic pain in Spinal cord injury patients Pain endpoints Crossover design