Explosive Synchronization of Brain Network Activity in Chronic Pain

Not Applicable

Recruiting

• Conditions: Fibromyalgia; Healthy Volunteers
• Interventions: Diagnostic Test: EEG; Diagnostic Test: Neuroimaging EEG/fMRI; Device: HD-tDCS treatments; Device: Sham HD-tDCS treatments

• Registration Number: NCT04606095
• Lead Sponsor: University of Michigan

Brief Summary

This project is being conducted to evaluate the impact of explosive synchronization (ES) and its treatment with non-invasive brain stimulation in fibromyalgia (FM). The study design has three components, however, only 2 aims are enrolling participants. The first part (Aim1) is a cross sectional assessment of brain network explosive synchronization activity, connectivity, and response to pain in healthy controls and age and sex-matched fibromyalgia patients; the third part (Aim 3) is a longitudinal assessment of fibromyalgia patients undergoing one week of sham followed by high-definition transcranial direct current stimulation (HD-tDCS) of the motor cortex (M1) or one week of ES HD-tDCS of a brain region identified from computer modelling (Aim 2).

Detailed Description

In the first part healthy controls (25 female/10 males) and fibromyalgia (25 female/10 males) participants that are enrolled in this phase will have 3 visits as well as a run-in observational period (up to a total of 33 days). During this time, participants will complete surveys, as well as have electroencephalograms (EEG) with quantitative sensory testing and functional Magnetic resonance imaging (fMRI).

Hypothesis: FM patients will display greater ES in the brain, compared to pain-free controls when assessed with EEG at rest. Furthermore, patients experiencing increased clinical pain, will display increases in ES metrics

In the third part FM patients will be enrolled (50) and receive treatment with either sham treatment followed by M1 HD-tDCS or sham treatment followed by ES HD-tDCS. These participants will also complete surveys and have neuroimaging EEG/MRI.

Hypothesis: Following a course of HD-tDCS targeted at either A.) the motor cortex (M1) or B.) an ES-sensitive region identified in Aim 2, FM patients will display decreased strength of ES conditions (correlation between node degree and frequency) as compared to Sham, when assessed with EEG. Moreover, the degree of pain reduction following HD-tDCS will correlate with the amount of reduction in these network parameters leading to ES. If unable to identify an ES-sensitive region using computer modeling in Aim 2, our hypothesis for motor cortex stimulation is that HD-tDCS at M1 will result in decreased ES conditions as compared to Sham, when assessed with EEG.

Basic Information
|
Recruitment & Eligibility
|
Study & Design
|
Trial Locations

Study Timeline

• Study First Submitted: 2020-10-06
• Study First Submitted QC: 2020-10-21
• Study First Posted: 2020-10-28
• Study Start: 2020-11-13
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-27
• Last Update Posted: 2024-03-28
• Primary Completion: 2025-10
• Study Completion: 2025-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

Not provided

Read More

Exclusion Criteria

Not provided

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Aim 3- HD-tDCS of ES	EEG	There will be two weeks of treatment in which participants will have 5 daily sessions of focused HD-tDCS or Sham per week.
Aim 1 - Healthy control	EEG	Participants will have three visits for this part along with a run-in observation period. An EEG with Quantitative Sensory Testing (QST) will be performed at visit 1 along with other measures. Additionally, the an MRI will be done at visit 2 along with other measures.
Aim 3- HD-tDCS of ES	HD-tDCS treatments	There will be two weeks of treatment in which participants will have 5 daily sessions of focused HD-tDCS or Sham per week.
Aim 3- HD-tDCS of ES	Sham HD-tDCS treatments	There will be two weeks of treatment in which participants will have 5 daily sessions of focused HD-tDCS or Sham per week.
Aim 3 - Sham	HD-tDCS treatments	There will be two weeks of treatment in which participants will have 5 daily sessions of focused HD-tDCS or Sham per week.
Aim 1 - Healthy control	Neuroimaging EEG/fMRI	Participants will have three visits for this part along with a run-in observation period. An EEG with Quantitative Sensory Testing (QST) will be performed at visit 1 along with other measures. Additionally, the an MRI will be done at visit 2 along with other measures.
Aim 3 - HD-tDCS of M1	HD-tDCS treatments	There will be two weeks of treatment in which participants will have 5 daily sessions of focused HD-tDCS or Sham per week.
Aim 3 - Sham	Sham HD-tDCS treatments	There will be two weeks of treatment in which participants will have 5 daily sessions of focused HD-tDCS or Sham per week.
Aim 1 - Fibromyalgia participant	EEG	Participants will have three visits for this part along with a run-in observation period. An EEG with Quantitative Sensory Testing (QST) will be performed at visit 1 along with other measures. Additionally, the an MRI will be done at visit 2 along with other measures.
Aim 3 - HD-tDCS of M1	Neuroimaging EEG/fMRI	There will be two weeks of treatment in which participants will have 5 daily sessions of focused HD-tDCS or Sham per week.
Aim 1 - Fibromyalgia participant	Neuroimaging EEG/fMRI	Participants will have three visits for this part along with a run-in observation period. An EEG with Quantitative Sensory Testing (QST) will be performed at visit 1 along with other measures. Additionally, the an MRI will be done at visit 2 along with other measures.
Aim 3 - HD-tDCS of M1	EEG	There will be two weeks of treatment in which participants will have 5 daily sessions of focused HD-tDCS or Sham per week.
Aim 3 - HD-tDCS of M1	Sham HD-tDCS treatments	There will be two weeks of treatment in which participants will have 5 daily sessions of focused HD-tDCS or Sham per week.
Aim 3- HD-tDCS of ES	Neuroimaging EEG/fMRI	There will be two weeks of treatment in which participants will have 5 daily sessions of focused HD-tDCS or Sham per week.
Aim 3 - Sham	EEG	There will be two weeks of treatment in which participants will have 5 daily sessions of focused HD-tDCS or Sham per week.
Aim 3 - Sham	Neuroimaging EEG/fMRI	There will be two weeks of treatment in which participants will have 5 daily sessions of focused HD-tDCS or Sham per week.

Primary Outcome Measures

Name	Time	Method
Aim 1 - Brain EEG metric of ES obtained at Visit 1: Correlation between EEG alpha band degree and frequency.	Visit 1 (day 0)	Correlation between EEG alpha band degree and frequency will be calculated as the primary outcome measure. Brain related EEG data will be analyzed using computer software designed for EEG data as well as Statistical Package for the Social Sciences (SPSS).
Aim 3 - Change in brain EEG metrics of ES: Change from visit 8 to visit 14 in correlation of EEG alpha band degree and frequency.	Visit 8 (approximately day 14- day18), Visit 14 (approximately day 28-32)	Change of correlation between EEG alpha band degree and frequency from visit 8 to visit 14 is the primary outcome. Brain related EEG data will be analyzed using computer software designed for EEG data as well as SPSS.

Secondary Outcome Measures

Name	Time	Method
Aim 1: Resting brain functional connectivity using functional magnetic resonance imaging obtained at Visit 2	Visit 2 (days 0-3)	Resting brain functional connectivity Z statistic will be assessed with functional magnetic resonance imaging (fMRI). The resting brain connectivity to the insula and Default Mode Network structures will be assessed with both seed based and independent component based fMRI analysis.
Aim 1: Insular Glx (glutamate + glutamine) using proton magnetic resonance spectroscopy obtained at Visit 2	Visit 2 (days 0-3)	The concentration of Glx (glutamate + glutamine) within the insular brain region, will be assessed with proton magnetic resonance spectroscopy (H-MRS). Analysis will be done with linear combination model software (LCModel).
Aim 3- Change in resting brain functional connectivity using functional magnetic resonance imaging from visit 8 to visit 14.	Visit 8 (approximately day 14- day18), Visit 14 (approximately day 28-32)	Change from visit 8 to visit 14 of resting brain functional connectivity Z statistic will be assessed with functional magnetic resonance imaging (fMRI). Change from visit 8 to visit 14 in resting brain connectivity of the insula and Default Mode Network structures will be assessed with seed based and independent component based fMRI analysis.
Aim 3- Change in insular Glx (glutamate + glutamine) using proton magnetic resonance spectroscopy from visit 8 to visit 14.	Visit 8 (approximately day 14- day18), Visit 14 (approximately day 28-32)	Change from visit 8 to visit 14 in the concentration of Glx (glutamate + glutamine) within the insular brain region, will be assessed with proton magnetic resonance spectroscopy (H-MRS). Analysis will be done with linear combination model software (LCModel).

Trial Locations

Locations (1)

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States