Study To Assess The Reproducibility And Sensitivity Of Quantitative Sensory Testing In Patients With Neuropathic Pain

Study Overview
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Brief Summary
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Conventional pain efficacy measures such as Visual Analogue Scores (VAS) are often unable to detect treatment efficacy in small-scale clinical trials. Combining conventional pain efficacy measures with quantitative sensory testing (QST) may provide more sensitive and informative outcome measures in clinical trials.

Detailed Description
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Methodology to assess reproducibility and sensitivity of quantitative sensory testing

Official Title
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A Randomized, Double Blind, Placebo Controlled, 2-Way Crossover Methodology Study Designed To Assess The Reproducibility And Sensitivity Of Quantitative Sensory Testing (QST) In Patients With Neuropathic Pain Treated With Pregabalin Vs Placebo

Conditions
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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: Neuropathic pain of peripheral origin demonstrating spontaneous ongoing pain and dynamic mechanical allodynia to brush stimuli. A present pain intensity score of 4 or more (out of 10) for spontaneous ongoing pain and brush-evoked allodynia at the skin area at screen. Stable analgesic medication (excluding pregabalin) for a minimum of 1 month prior to the start of study. Exclusion Criteria: Patients who have undergone neurolytic or neurosurgical therapy. Patients who have trigeminal neuralgia, central pain (due to cerebrovascular lesions, multiple sclerosis and traumatic spinal cord injuries), complex regional pain syndrome (Type I and II), and phantom limb pain. Patients who have previously been treated with pregabalin.

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: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active drug<br> | Drug: Pregabalin<br>* Dose titration according to following regimen: 75mg BID for 3 days; 150mg for 4 days; 225mg BID for 4 days; 300mg BID for 17 days. Dose reduced for renally impaired patients<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* BID dosing for 28 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Dynamic Allodynia Intensity at Visits 3 and 6 and Visits 4 and 7 | Five strokes applied with a standardized brush (somedic) across the painful site, 6cm long and at a control site to allow the participants to appreciate any difference. A painful and clearly dysaesthetic (unpleasant) sensation was considered as representing brush allodynia (whereas a strange or tickly sensation provoked by the brush was not). After each brush stimuli participants were asked to give a pain rating using 11-point numerical rating scale (NRS) where 0=no pain and 10=worst pain imaginable. The average of 5 brush strokes was calculated to obtain the mean score. | Week 3 (Visits 3 and 6) and Week 4 (Visits 4 and 7) of each period | 
| Mean Change From Baseline in Dynamic Allodynia Area at Visits 3 and 6 and Visits 4 and 7 | Dynamic area brush in cm^2: calculated from 8 measured distances by calculating the area of an octagon. The angle between each pair of lines was 45 degrees at point c. The area of the octagon was found by totaling the areas of the 8 triangles. Octagon with 8 radial lengths from center to the outside. Area = Σ ( ½ length * perpendicular height); Σ ( ½ ri * sin(45) r(i+1) ) = Σ ( (ri * r(i+1) )/2√2)). (where ri, i=1 to 8, were the eight radial lengths) | Week 3 (Visits 3 and 6) and Week 4 (Visits 4 and 7) of each period | 
| Mean Change From Baseline in Mechanical Pain Sensitivity (Von Frey) at Visits 3 and 6 and Visits 4 and 7 | Sensitivity to mechanical pain stimuli was tested using calibrated Von Frey monofilaments. To obtain a stimulus-response-function, seven different Von Frey monofilaments (size 8 to 512 mN, force increased by a factor of two from filament to filament) applied three times each; each stimulus was participant-rated using 11-point NRS where 0=no pain and 10=worst pain imaginable. If a score of 8 or more was reported for a given intensity no stronger stimuli was applied. Von Frey stimulus was applied to the skin for 1 to 2 seconds. The average of 3 ratings was calculated for the mean score. | Week 3 (Visits 3 and 6) and Week 4 (Visits 4 and 7) of each period | 
| Mean Change From Baseline in Punctate Allodynia Area (Von Frey) at Visits 3 and 6 and Visits 4 and 7 | Punctate allodynia area in cm^2: calculated from 8 measured distances by calculating the area of an octagon. The angle between each pair of lines was 45 degrees at point c. The area of the octagon was found by totaling the areas of the 8 triangles. Octagon with 8 radial lengths from center to the outside. Area = Σ ( ½ length * perpendicular height); Σ ( ½ ri * sin(45) r(i+1) ) = Σ ( (ri * r(i+1) )/2√2)). (where ri, i=1 to 8, were the eight radial lengths) | Week 3 (Visits 3 and 6) and Week 4 (Visits 4 and 7) of each period | 
| Mean Change From Baseline in Cold Pain Sensitivity at Visits 3 and 6 and Visits 4 and 7 | Duration of thermal stimuli was 2 seconds and an intensity that is increased in steps of 5 degrees celsius for cold stimuli (between 5 and 20 degrees celsius). Thermal pain sensitivity was participant-rated using 11-point NRS where 0=no pain and 10=worst pain imaginable. The average of 2 ratings was calculated to get the mean score. | Week 3 (Visits 3 and 6) and Week 4 (Visits 4 and 7) of each period | 
| Mean Change From Baseline in Heat Pain Sensitivity at Visits 3 and 6 and Visits 4 and 7 | Duration of thermal stimuli was 2 seconds and an intensity that is increased in steps of 4 degrees celsius for heat stimuli (between 40 and 50 degrees celsius). Thermal pain sensitivity was participant-rated using 11-point NRS where 0=no pain and 10=worst pain imaginable. The average of 2 ratings was calculated to get the mean score. | Week 3 (Visits 3 and 6) and Week 4 (Visits 4 and 7) of each period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Weekly Pain Score From the Daily Diary at Visits 3 and 6 and Visits 4 and 7 | Daily pain diary: participant-rated pain during the past 24 hours rated on an 11 point NRS scale where 0=no pain and 10=worst possible pain. For a given week, the pain response was the average of the 7 daily entries for that week, or average of the available data for that week if fewer than 7 entries were recorded (>=1 daily pain score for any given week required). The endpoint for each week consisted of the change from baseline in average pain score (follow-up value minus baseline). | Week 3 (Visits 3 and 6) and Week 4 (Visits 4 and 7) of each period | 
| Mean Change From Baseline in Patient's Global Impression of Change (PGIC) at Visits 3 and 6 and Visits 4 and 7 | PGIC: participant-rated assessment measuring change in participant's overall status on a 7-point scale from 1=very much improved to 7=very much worse. | Week 3 (Visits 3 and 6) and Week 4 (Visits 4 and 7) of each period | 
| Mean Change From Baseline in Test-Day Global Pain Intensity at Visits 3 and 6 and Visits 4 and 7 | Global pain: participant-rated pain using the test-day global pain scale, consisting of an 11-point NRS where 0 = no pain and 10 = worst possible pain. Participants described intensity of pain in response to How intense is your pain today? | Week 3 (Visits 3 and 6) and Week 4 (Visits 4 and 7) of each period | 
| Mean Change From Baseline in Neuropathic Pain Symptom Inventory (NPSI) Total Score at Visits 4 and 7 | NPSI: 10-item self-administered questionnaire assessing 5 dimensions of pain (burning superficial spontaneous pain, pressing deep spontaneous pain, paroxysmal pain, evoked pain, and paresthesia/dysesthesia). Each item consists of a question about the specific qualities of pain and an 11-point numerical scale range: 0 (absence of pain) to 10 (maximum intensity imaginable), and 2 temporal items related to spontaneous and paroxysmal pain. Maximum total score possible = 100. | Week 4 (Visits 4 and 7) of each period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Methodology, Quantitative Sensory Testing, Neuropathies Pain, Pregabalin