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

This study has been completed.
Sponsor:
Information provided by:
Pfizer
ClinicalTrials.gov Identifier:
NCT01117766
First received: May 4, 2010
Last updated: February 14, 2011
Last verified: February 2011
  Purpose

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.


Condition Intervention
Neuropathic Pain
Drug: Pregabalin
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Mean Change From Baseline in Dynamic Allodynia Intensity at Visits 3 and 6 and Visits 4 and 7 [ Time Frame: Week 3 (Visits 3 and 6) and Week 4 (Visits 4 and 7) of each period ] [ Designated as safety issue: No ]
    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.

  • Mean Change From Baseline in Dynamic Allodynia Area at Visits 3 and 6 and Visits 4 and 7 [ Time Frame: Week 3 (Visits 3 and 6) and Week 4 (Visits 4 and 7) of each period ] [ Designated as safety issue: No ]
    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)

  • Mean Change From Baseline in Mechanical Pain Sensitivity (Von Frey) at Visits 3 and 6 and Visits 4 and 7 [ Time Frame: Week 3 (Visits 3 and 6) and Week 4 (Visits 4 and 7) of each period ] [ Designated as safety issue: No ]
    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.

  • Mean Change From Baseline in Punctate Allodynia Area (Von Frey) at Visits 3 and 6 and Visits 4 and 7 [ Time Frame: Week 3 (Visits 3 and 6) and Week 4 (Visits 4 and 7) of each period ] [ Designated as safety issue: No ]
    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)

  • Mean Change From Baseline in Cold Pain Sensitivity at Visits 3 and 6 and Visits 4 and 7 [ Time Frame: Week 3 (Visits 3 and 6) and Week 4 (Visits 4 and 7) of each period ] [ Designated as safety issue: No ]
    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.

  • Mean Change From Baseline in Heat Pain Sensitivity at Visits 3 and 6 and Visits 4 and 7 [ Time Frame: Week 3 (Visits 3 and 6) and Week 4 (Visits 4 and 7) of each period ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Mean Change From Baseline in Weekly Pain Score From the Daily Diary at Visits 3 and 6 and Visits 4 and 7 [ Time Frame: Week 3 (Visits 3 and 6) and Week 4 (Visits 4 and 7) of each period ] [ Designated as safety issue: No ]
    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).

  • Mean Change From Baseline in Patient's Global Impression of Change (PGIC) at Visits 3 and 6 and Visits 4 and 7 [ Time Frame: Week 3 (Visits 3 and 6) and Week 4 (Visits 4 and 7) of each period ] [ Designated as safety issue: No ]
    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.

  • Mean Change From Baseline in Test-Day Global Pain Intensity at Visits 3 and 6 and Visits 4 and 7 [ Time Frame: Week 3 (Visits 3 and 6) and Week 4 (Visits 4 and 7) of each period ] [ Designated as safety issue: No ]
    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?"

  • Mean Change From Baseline in Neuropathic Pain Symptom Inventory (NPSI) Total Score at Visits 4 and 7 [ Time Frame: Week 4 (Visits 4 and 7) of each period ] [ Designated as safety issue: No ]
    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.


Enrollment: 31
Study Start Date: December 2006
Study Completion Date: September 2009
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Active drug Drug: Pregabalin
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
Placebo Comparator: Placebo Drug: Placebo
BID dosing for 28 days

Detailed Description:

Methodology to assess reproducibility and sensitivity of quantitative sensory testing

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01117766

Locations
Austria
Pfizer Investigational Site
Vienna, Austria, A-1090
Belgium
Pfizer Investigational Site
Bruxelles, Belgium, 1070
France
Pfizer Investigational Site
Boulogne Billancourt, France, 92100
United Kingdom
Pfizer Investigational Site
Liverpool, United Kingdom, L9 7AL
Pfizer Investigational Site
London, United Kingdom, SW10 9NH
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Director, Clinical Trial Disclosure Group, Pfizer, Inc.
ClinicalTrials.gov Identifier: NCT01117766     History of Changes
Other Study ID Numbers: A9011015
Study First Received: May 4, 2010
Results First Received: September 1, 2010
Last Updated: February 14, 2011
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Pfizer:
Methodology
Quantitative Sensory Testing
Neuropathies Pain
Pregabalin

Additional relevant MeSH terms:
Neuralgia
Pain
Neurologic Manifestations
Nervous System Diseases
Peripheral Nervous System Diseases
Neuromuscular Diseases
Signs and Symptoms
Pregabalin
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Anticonvulsants
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents

ClinicalTrials.gov processed this record on August 28, 2014