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Completed

NCT Number: NCT03075254

Central Mechanisms of Chronic Pain and Fatigue Subtitle: Functional Imaging of Brain and Spinal Cord

Chronic pain and fatigue are characterized by peripheral and central mechanisms including low pain thresholds, temporal summation, peripheral and central sensitization. This application will focus on central factors of chronic pain and fatigue. Functional brain imaging will be used to characterized brain and spinal cord abnormalities that contribute to the mechanisms of these disorders.

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Key information

About this study

Chronic fatigue (ME/CFS) and fibromyalgia syndrome (FM) are a chronic musculoskeletal pain disorder that predominantly afflicts women. Frequently associated insomnia, cognitive abnormalities, and fatigue may lead to early disability. No consistent soft tissue abnormalities have been identified so far in these patients. The cause of these disorders is unknown, no highly effective treatment is available and the current methods of diagnosis are imprecise and unreliable. The Investigators previously used quantitative sensory testing to improve upon diagnoses of these disorders by supplementing the current procedure of manipulating defined pressure points by hand and noting the presence or absence of pain. The quantitative methods of evaluation involve repetitive application of brief, non-injurious thermal/mechanical stimulation that normally produces a moderate degree of temporal summation of sensation intensity. The patients and normal control subjects will verbally rate the magnitude of late sensations elicited by each stimulus, using a numerical scale. Chronic pain in these patients results, at least partially, from exaggerated activation of central N-methyl-D-aspartate (NMDA) receptors as a result of enhanced input from unmyelinated peripheral afferent nerve fibers supplying deep tissues. Temporal summation of second pain can lead to central sensitization with subsequent signs of hyperalgesia and allodynia. Functional brain imaging of ME/CFS and FM patients, as proposed in this study, will be used to document their ratings of repetitive experimental stimuli and the resulting pain augmentation. Successful completion of this study will provide a new method for the evaluation of chronic pain/fatigue mechanism and their response to therapy.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • diagnosis of FM will require a history of chronic widespread pain as well as the presence of at least eleven out of eighteen paired tender points.
  • diagnosis of ME/CFS will require a history of chronic fatigue persisting or relapsing for more than 6 months as well as the presence of at least four out of eight designated symptoms.
  • willing to reduce anti-depressants to low levels like amitriptyline 10 mg/day, trazodone 50 mg/day, citalopram 20 mg/day, for at least five half-lives of the medication.

Exclusion criteria

  • Patients unwilling or unable to discontinue or modify analgesics, hypnotics, anxiolytics, or anti-depressants during the study period will be excluded from this trial.

Treatment and study plan

A Peltier for Sensory testing

Device

Subjects will be trained to rate the magnitude of late sensations elicited following brief (700 msec) contact of a preheated thermode with the glabrous (palmar) skin of either hand/foot either numerically or using a visual analogue scale.

Other names: Heat Foil device

functional magnetic resonance imaging for Brain Neuroimaging

Device

to evaluate baseline changes in regional cerebral blood flow to nociceptive thermal stimuli applied to the extremities of FM patients and healthy volunteers.

Other names: fMRI

fMRI for Spinal Cord Neuroimaging

Device

The subjects will be positioned supine and immobilized by means of a padded head support. The spinous process of the first thoracic vertebra (T1) will be aligned with the center of surface Neuro - coil. This coil will be employed for both transmission of radio-frequency (RF) pulses and detection of the magnetic resonance (MR) signal. A modified FLASH sequence will be employed to obtain Blood Oxygen Level Dependent (BOLD)-sensitive images of the spinal cord.

Other names: functional magnetic resonance imaging

Primary outcomes

  1. Change in experimental pain from heat pulses to the upper extremities

    Time frame: 3 intervals of 30 seconds each

    Numerical ratings from 0 to 100 are tied to verbal descriptors in increments of 5, to standardize the scale, and ratings in increments of 5 are permitted. Ratings of 0 and 15 designate non-painful sensations of warmth (5 = threshold for warmth, 15 = suprathreshold warmth). A rating of 20 = threshold for heat pain, 30 = very weak pain, 40 = weak pain, 50 = moderate pain, 60 = slightly strong pain, 70 = strong pain, 80 = very strong pain, 90 = extreme strong pain, and 100 = the most intense pain imaginable

  2. Change in experimental Pain from mechanical stimulation to the upper extremities and the shoulder

    Time frame: 3 intervals of 30 seconds each

    Numerical ratings from 0 to 100 are tied to verbal descriptors in increments of 5, to standardize the scale, and ratings in increments of 5 are permitted. Ratings of 0 and 15 designate non-painful sensations of warmth (5 = threshold for warmth, 15 = suprathreshold warmth). A rating of 20 = threshold for heat pain, 30 = very weak pain, 40 = weak pain, 50 = moderate pain, 60 = slightly strong pain, 70 = strong pain, 80 = very strong pain, 90 = extreme strong pain, and 100 = the most intense pain imaginable

Secondary outcomes

  1. Change in Fatigue Ratings

    Time frame: baseline and up to 3 hours.

    Visual analogue scale ratings (0-10) on a 15 cm mechanical scale. The scale is limited on the left by "no fatigue at all" and on the right by "most intense fatigue imaginable"

Sponsors and collaborators

Lead sponsor

University of Florida

Other

Registry information

Important dates

Study start
2017
Primary completion
2024
Study completion
2024
First posted
Mar 9, 2017
Registry last updated
Jan 27, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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