An fMRI Study Of Brain Response In Patients With Fibromyalgia

January 20, 2021 updated by: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Methodology study

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
27

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Pfizer Investigational Site
      • Ann Arbor, Michigan, United States, 48106
        • Pfizer Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Pregabalin, then placebo
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.
Experimental: Placebo, then pregabalin
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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)
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.
Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51)
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)
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.
Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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)
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.
Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51)
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)
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.
Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51)
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)
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.
Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51)
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)
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.
Baseline/Pre-dose (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51)
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)
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.
Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51)
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)
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.
Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51)
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)
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.
Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51)
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)
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.
Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51)
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)
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.
Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51)
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)
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.
Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51)
Sphygmomanometry Evoked Allodynia in Relation to the Blood Pressure (BP) Value at Which Allodynia Was Evoked
Time Frame: Day 58
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.
Day 58
Pain at the Bilateral Epicondyle Tender Points Assessed Using American College of Rheumatology (ACR) Classification Criteria
Time Frame: Day 58
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.
Day 58

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Hospital Anxiety and Depression Scale (HADS): Anxiety Total Score Including Outliers
Time Frame: Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51)
A participant rated questionnaire with 2 subscales. HADS-A assessed state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks); HADS-D assessed state of lost interest and diminished pleasure response (lowering of hedonic tone). Each subscale comprised of 7 items with range 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Total score 0 to 21 for each subscale; higher score indicated greater severity of anxiety and depression symptoms. Any observation with a studentized residual >3 or <-3 was considered an outlier.
Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51)
Hospital Anxiety and Depression Scale (HADS): Depression Total Score Including Outliers
Time Frame: Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51)
A participant rated questionnaire with 2 subscales. HADS-A assessed state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks); HADS-D assessed state of lost interest and diminished pleasure response (lowering of hedonic tone). Each subscale comprised of 7 items with range 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Total score 0 to 21 for each subscale; higher score indicated greater severity of anxiety and depression symptoms. Any observation with a studentized residual >3 or <-3 was considered an outlier.
Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51)
Pain Catastrophizing Scale (PCS) Including Outliers
Time Frame: Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51)
PCS is a participant rated 13-item instrument to measure the presence and severity of catastrophizing. Scored 0 (not at all) to 4 (all the time) to statements such as "When I'm in pain…I worry all the time about whether the pain will end". All 13 statements start with "When I'm in pain…". Total score ranged from 0 to 52; higher scores reflected greater impairment. 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.
Baseline (Day 8, Day 37), Post-dose (Period 1/Day 22, Period 2/Day 51)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2009

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 1, 2011

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 1, 2011

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 25, 2008

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 25, 2008

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 26, 2008

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 22, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 20, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • A0081211

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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