An fMRI Study Of Brain Response In Patients With Fibromyalgia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00760474
First received: September 25, 2008
Last updated: June 22, 2012
Last verified: June 2012

September 25, 2008
June 22, 2012
January 2009
March 2011   (final data collection date for primary outcome measure)
  • Glutamine/Creatine (Gln/Cr) and Glutamate/Creatine (Glu/Cr) Ratios Measured by Proton Magnetic Resonance Spectroscopy (1H-MRS) [ Time Frame: Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51) ] [ Designated as safety issue: No ]
    Single voxel spectra obtained from the anterior and posterior right insula at rest to compare ratios for Gln/Cr, Glu/Cr, and combined Glutamate + Glutamine (Glx/Cr) for pregabalin and placebo. Gln, Glu, Glx calculated as ratios to the internal standard creatine.
  • Voxel-wise Blood Oxygen Level Dependent (BOLD) Using Functional Magnetic Resonance Imaging (fMRI) of Brain Activation Signals in Response to Blunt Pressure Pain: Percent Change in BOLD Activations Including Outliers [ Time Frame: Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51) ] [ Designated as safety issue: No ]
    BOLD fMRI imaging modality to assess brain activation signals across the whole brain in defined Region of Interest (ROI) brain regions in response to blunt pressure pain; acquired during resting state (no evoked pain) and during evoked pain (thumb pressure device with non-painful pressure, 2 kilograms [kg] pressure/equal stimulus conditions, and high pain pressure/up to 10 kg). Estimated as magnitude (percent change) of the betas representing brain signal activation associated with pressure induced pain. Any observation with a studentized residual >3 or <-3 was considered an outlier.
  • Magnetic resonance imaging will be used to measure brain glutamine and glutamate levels. [ Time Frame: 4 times on study (last time at Day 51) ] [ Designated as safety issue: No ]
  • fMRI brain activation signals will be evaluated across the whole brain and in defined brain regions in response to blunt pressure pain and to control visual stimuli. [ Time Frame: 4 times on study (last time at Day 51) ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00760474 on ClinicalTrials.gov Archive Site
  • Voxel-wise Blood Oxygen Level Dependent (BOLD) Using Functional Magnetic Resonance Imaging (fMRI) of Brain Activation Signals in Response to a Control Visual (Checkerboard) Stimuli [ Time Frame: Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51) ] [ Designated as safety issue: No ]
    BOLD fMRI imaging modality to assess brain activation signals across the whole brain in defined ROI brain regions in response to checkerboard visual stimuli (flashing at 8 hertz [Hz]). Reported as percent change between the pre-dose (baseline) and post-dose values.
  • Resting State Brain Activity (Connectivity Analysis) Assessed by Temporal Correlations in Low Frequency fMRI BOLD Signals Across Pain Processing Regions [ Time Frame: Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51) ] [ Designated as safety issue: No ]
    Resting state brain activity assessed for correlation of brain seed region (pIns, anIns) to ROI connectivity at baseline (pre-dose) and post-dose (pre minus post) measured using z-score (mean of 0, standard deviation [SD] of 1); range approximately -3 to +3. Positive (+) z-scores reflect greater connectivity (+correlation between seed region and ROI). Negative (-) z-scores reflect -connectivity (anti-correlation between seed region and ROI). ROIs include PCC and IPL from within the default mode network (DMN). DMN is a constellation of regions in which connectivity is augmented in fibromyalgia.
  • Gracely Box Scales for Pain Intensity (GBSint) Including Outliers [ Time Frame: Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51) ] [ Designated as safety issue: No ]
    Minimum and maximum pain intensity acquired during resting state (no evoked pain) and during evoked pain (thumb pressure device with non-painful pressure, 2 kg pressure/equal stimulus conditions, and high pain pressure/up to 10 kg) measured during fMRI and scored from 0 (no pain sensation) to 20 (extremely intense). Baseline and Post-dose data for Period 1 and Period 2 summarized as Least Squares Mean (LS Mean). Any observation with a studentized residual >3 or <-3 was considered an outlier.
  • Gracely Box Scales for Pain Unpleasantness (GBSunp) Including Outliers [ Time Frame: Baseline/Pre-dose (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51) ] [ Designated as safety issue: No ]
    Minimum and maximum pain unpleasantness acquired during resting state (no evoked pain) and during evoked pain (thumb pressure device with non-painful pressure, 2 kg pressure/equal stimulus conditions, and high pain pressure/up to 10 kg) measured during fMRI and scored from 0 (neutral) to 20 (very intolerable). Baseline and Post-dose data for Period 1 and Period 2 summarized as LS Mean. Any observation with a studentized residual >3 or <-3 was considered an outlier.
  • Daily Pain Diary Numeric Rating Scale (NRS) Item From the Modified Brief Pain Inventory (mBPI) for Assessment of Clinical Pain: 7 Day Average Pain Score Including Outliers [ Time Frame: Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51) ] [ Designated as safety issue: No ]
    The daily pain diary consisted of the mBPI item regarding participant-rated average of pain over the past 24 hours. Scored on an 11-point numeric scale ranging from 0 (no pain) to 10 (pain as bad as you can imagine). The 7 day average pain score was defined as the mean daily pain NRS value for the last 7 days prior to fMRI scanning visit. Baseline and Post-dose data for Period 1 and Period 2 summarized as LS Mean. Any observation with a studentized residual >3 or <-3 was considered an outlier.
  • Daily Pain Diary Numeric Rating Scale (NRS) Item From the Modified Brief Pain Inventory (mBPI) for Assessment of Clinical Pain: 3 Day Average Pain Score Including Outliers [ Time Frame: Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51) ] [ Designated as safety issue: No ]
    The daily pain diary consisted of the mBPI item regarding participant-rated average of pain over the past 24 hours. Scored on an 11-point numeric scale ranging from 0 (no pain) to 10 (pain as bad as you can imagine). The 3 day average pain score was defined as the mean daily pain NRS value for the last 3 days prior to fMRI scanning visit. Baseline and Post-dose data for Period 1 and Period 2 summarized as LS Mean. Any observation with a studentized residual >3 or <-3 was considered an outlier.
  • Daily Pain Diary Numeric Rating Scale (NRS) Item From the Modified Brief Pain Inventory (mBPI) for Assessment of Clinical Pain: Individual Daily Pain Score Including Outliers [ Time Frame: Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51) ] [ Designated as safety issue: No ]
    The daily pain diary consisted of the mBPI item regarding participant-rated average of pain over the past 24 hours. Scored on an 11-point numeric scale ranging from 0 (no pain) to 10 (pain as bad as you can imagine). The individual daily pain score was defined as the final score recorded in the last pain diary of the treatment period 24 hours prior to fMRI scanning visit. Baseline and Post-dose data for Period 1 and Period 2 summarized as LS Mean. Any observation with a studentized residual >3 or <-3 was considered an outlier.
  • Short-Form McGill Pain Questionnaire (SF-MPQ): Affective Total Score Including Outliers [ Time Frame: Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51) ] [ Designated as safety issue: No ]
    SF-MPQ was completed to assess pain over the past week and to assess present pain and consists of 15 pain descriptors: sensory dimension of pain experience (sum of items 1 to 11) and affective dimension (sum of items 12 to 15). Each descriptor was ranked by participant on a 4-point intensity scale (0=none to 3=severe) and totaled in each subclass (sensory range 0 to 33; affective range 0 to 12); higher scores indicated higher pain/impact. Baseline and Post-dose data for Period 1 and Period 2 summarized as LS Mean. Any observation with a studentized residual >3 or <-3 was considered an outlier.
  • Short-Form McGill Pain Questionnaire (SF-MPQ): Sensory Total Score Including Outliers [ Time Frame: Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51) ] [ Designated as safety issue: No ]
    SF-MPQ was completed to assess pain over the past week and to assess present pain and consists of 15 pain descriptors: sensory dimension of pain experience (sum of items 1 to 11) and affective dimension (sum of items 12 to 15). Each descriptor was ranked by participant on a 4-point intensity scale (0=none to 3=severe) and totaled in each subclass (sensory range 0 to 33; affective range 0 to 12); higher scores indicated higher pain/impact. Baseline and Post-dose data for Period 1 and Period 2 summarized as LS Mean. Any observation with a studentized residual >3 or <-3 was considered an outlier.
  • Short-Form McGill Pain Questionnaire (SF-MPQ): Overall Score Including Outliers [ Time Frame: Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51) ] [ Designated as safety issue: No ]
    SF-MPQ was completed to assess pain over the past week and to assess present pain and consists of 15 pain descriptors: sensory dimension of pain experience (sum of items 1 to 11) and affective dimension (sum of items 12 to 15). Each descriptor was ranked by the participant on a 4-point intensity scale (0=none to 3=severe) and totaled in each subclass (sensory range 0 to 33; affective range 0 to 12). Total (overall) score was sum of items 1 to 15, range 0 to 45; higher scores indicated higher pain/impact. Any observation with a studentized residual >3 or <-3 was considered an outlier.
  • Sphygmomanometry Evoked Allodynia in Relation to the Blood Pressure (BP) Value at Which Allodynia Was Evoked [ Time Frame: Day 58 ] [ Designated as safety issue: No ]
    BP cuff evoked allodynia assessed based on participant response to the following question "When I take your blood pressure, tell me if the cuff's pressure is painful". A standard BP cuff was inflated at approximately 10 millimeters of mercury (mm Hg) per second up to 180 mm Hg or to point when participant experienced pain; performed 3 times on each arm whether or not pain was reported. If no pain elicited at 180 mm Hg, it was recorded that no sphygmomanometry-evoked allodynia occurred. If pain was reported, value (in mm Hg) at which pain first occured was recorded for each of the assessments.
  • Pain at the Bilateral Epicondyle Tender Points Assessed Using American College of Rheumatology (ACR) Classification Criteria [ Time Frame: Day 58 ] [ Designated as safety issue: No ]
    Participant rated severity of pain upon application of 4 kilograms (kg) pressure via dolorimeter at the bilateral epicondyle tender points (2 tender points, 2 centimeters distal to the epicondyles) described in the American College of Rheumatology (ACR) classification criteria and scored on a 0 (no pain) to 10 (worst possible pain) rating scale. Each arm was to be assessed for any pain (one point on each arm) with the application of pressure.
  • Pain will be evaluated using the Gracely Box Scales several times during each imaging session. [ Time Frame: 5 times on study (last time on Day 51) ] [ Designated as safety issue: No ]
  • The modified Brief Inventory daily pain diary will be used to evaluate clinical pain. [ Time Frame: Daily, Days 1-51 ] [ Designated as safety issue: No ]
  • The Short-Form McGill Pain Questionnaire will be used to evaluate pain. [ Time Frame: 4 times on study (last time Day 51) ] [ Designated as safety issue: No ]
  • The Hospital Anxiety and Depression Scale will be used to evaluate anxiety and depression levels. [ Time Frame: 4 times on study (last time Day 51) ] [ Designated as safety issue: No ]
  • The Pain Catastrophizing Scale will be used to evaluate the extent of catastrophizing. [ Time Frame: 4 times on study (last time Day 51) ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
An fMRI Study Of Brain Response In Patients With Fibromyalgia
A Double-Blind, Placebo-Controlled Cross-Over Study In Fibromyalgia Subjects To Examine Effects Of Pregabalin On Brain Response To Mechanical Pain As Assessed By Functional Magnetic Resonance Imaging, Proton Magnetic Resonance Spectroscopy And Subjective Ratings

The purpose of this study is to explore how pregabalin works in patients with fibromyalgia by evaluating brain imaging signals. To find out whether fMRI (functional magnetic resonance imaging) is an efficient way to show whether new pain medications are effective in treating fibromyalgia.

Methodology study

Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Fibromyalgia
  • Drug: Pregabalin, then placebo
    Placebo and pregabalin will be given orally twice daily in capsules at different times during the course of the study. The highest dose of pregabalin to be used in the study is 450 mg/day.
  • Drug: Placebo, then pregabalin
    Placebo and pregabalin will be given orally twice daily in capsules at different times during the course of the study. The highest dose of pregabalin to be used in the study is 450 mg/day.
  • Experimental: Pregabalin, then placebo
    Intervention: Drug: Pregabalin, then placebo
  • Experimental: Placebo, then pregabalin
    Intervention: Drug: Placebo, then pregabalin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
27
March 2011
March 2011   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Women must have pain due to fibromyalgia
  • Fibromyalgia must have been diagnosed at least 6 months prior to be eligible for this study

Exclusion Criteria:

  • Patients with severe depression or other serious illness, who are left-handed, or who are pregnant or nursing are not eligible for this study.
Female
18 Years to 70 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00760474
A0081211
No
Pfizer
Pfizer
Not Provided
Study Director: Pfizer CT.gov Call Center Pfizer
Pfizer
June 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP