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

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

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.

Study Overview

• Status: Terminated
• Conditions: Spinal Cord Injuries
• Intervention / Treatment: Drug: Pregabalin; Drug: Placebo for pregabalin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Randwick, New South Wales, Australia, 2031
      • Pfizer Investigational Site
    • St Leonards, New South Wales, Australia, 2065
      • Pfizer Investigational Site
    • Warrawong, New South Wales, Australia, 2502
      • Pfizer Investigational Site
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pregabalin	Drug: Pregabalin; Pregabalin 150mg capsules BID for 7.5 days
Other: Placebo	Drug: Placebo for pregabalin; Placebo capsules BID for 7.5 days

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: February 1, 2007
• Primary Completion (Actual): October 1, 2008
• Study Completion (Actual): October 1, 2008

Study Registration Dates

• First Submitted: September 15, 2009
• First Submitted That Met QC Criteria: September 15, 2009
• First Posted (Estimate): September 16, 2009

Study Record Updates

• Last Update Posted (Actual): January 25, 2021
• Last Update Submitted That Met QC Criteria: January 21, 2021
• Last Verified: January 1, 2010

More Information

Terms related to this study

• Keywords: Clinical Trial Methodology study Neuropathic pain in Spinal cord injury patients Pain endpoints Crossover design
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Trauma, Nervous System; Spinal Cord Diseases; Spinal Cord Injuries; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anti-Anxiety Agents; Anticonvulsants; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Pregabalin
• Other Study ID Numbers: A0081141