Explosive Synchronization of Brain Network Activity in Chronic Pain

NCT ID: NCT04606095

Last Updated: 2025-11-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

150 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-11-13

Study Completion Date

2026-02-20

Brief Summary

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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

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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.

After consultation with and approval by NIH from September through November 2024, and IRB approval in January 2025, the testing involved for outcome measures 5 and 6 was removed for future participants, thus effectively demoting those outcome measures to exploratory.

Conditions

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Fibromyalgia Healthy Volunteers

Keywords

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Explosive synchronization

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

This study can run Aims 1 and 3 and the same time. Females that have FM can participate in Aim 3.
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors
The statistician and the study principal investigator will remain blinded as to which data arise from HD-tDCS and Sham, until the study database is locked. The only study personnel that will not be blinded are the staff performing treatment and the project manager, in order to facilitate safety and treatment delivery.

Study Groups

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Aim 1 - Healthy control

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.

Group Type EXPERIMENTAL

EEG

Intervention Type DIAGNOSTIC_TEST

EEG with QST (evoked Pain and Visual Stimulation Assessment)

Neuroimaging EEG/fMRI (Aim 1)

Intervention Type DIAGNOSTIC_TEST

This will be done to monitor areas of the brain that are involved in thinking and processing pain. The scanner stimulates the brain to send out signals that will be recorded and analyzed. Additionally, during the MRI the participants brain's electrical activity with will be measured with an EEG machine for part of the MRI. About halfway through the scan, participants will have the EEG equipment removed and then will return to the fMRI scanner for a few additional scans.

Aim 1 - Fibromyalgia participant

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.

Group Type EXPERIMENTAL

EEG

Intervention Type DIAGNOSTIC_TEST

EEG with QST (evoked Pain and Visual Stimulation Assessment)

Neuroimaging EEG/fMRI (Aim 1)

Intervention Type DIAGNOSTIC_TEST

This will be done to monitor areas of the brain that are involved in thinking and processing pain. The scanner stimulates the brain to send out signals that will be recorded and analyzed. Additionally, during the MRI the participants brain's electrical activity with will be measured with an EEG machine for part of the MRI. About halfway through the scan, participants will have the EEG equipment removed and then will return to the fMRI scanner for a few additional scans.

Aim 3 - HD-tDCS of M1

There will be two weeks of treatment in which participants will have 5 daily sessions of focused HD-tDCS or Sham per week.

Group Type EXPERIMENTAL

EEG

Intervention Type DIAGNOSTIC_TEST

EEG with QST (evoked Pain and Visual Stimulation Assessment)

HD-tDCS treatments

Intervention Type DEVICE

HD-tDCS treatments (5 active and 5 sham)

Sham HD-tDCS treatments

Intervention Type DEVICE

HD-tDCS treatments (5 active and 5 sham)

Neuroimaging EEG/fMRI (Aim 3)

Intervention Type DIAGNOSTIC_TEST

This will be done to monitor areas of the brain that are involved in thinking and processing pain. The scanner stimulates the brain to send out signals that will be recorded and analyzed. Additionally, during the MRI the participants brain's electrical activity with will be measured with an EEG machine for part of the MRI. About halfway through the scan, participants will have the EEG equipment removed and then (for participants prior to January 2025) will return to the fMRI scanner for a few additional scans.

Aim 3- HD-tDCS of ES

There will be two weeks of treatment in which participants will have 5 daily sessions of focused HD-tDCS or Sham per week.

Group Type EXPERIMENTAL

EEG

Intervention Type DIAGNOSTIC_TEST

EEG with QST (evoked Pain and Visual Stimulation Assessment)

HD-tDCS treatments

Intervention Type DEVICE

HD-tDCS treatments (5 active and 5 sham)

Sham HD-tDCS treatments

Intervention Type DEVICE

HD-tDCS treatments (5 active and 5 sham)

Neuroimaging EEG/fMRI (Aim 3)

Intervention Type DIAGNOSTIC_TEST

This will be done to monitor areas of the brain that are involved in thinking and processing pain. The scanner stimulates the brain to send out signals that will be recorded and analyzed. Additionally, during the MRI the participants brain's electrical activity with will be measured with an EEG machine for part of the MRI. About halfway through the scan, participants will have the EEG equipment removed and then (for participants prior to January 2025) will return to the fMRI scanner for a few additional scans.

Aim 3 - Sham

There will be two weeks of treatment in which participants will have 5 daily sessions of focused HD-tDCS or Sham per week.

Group Type SHAM_COMPARATOR

EEG

Intervention Type DIAGNOSTIC_TEST

EEG with QST (evoked Pain and Visual Stimulation Assessment)

HD-tDCS treatments

Intervention Type DEVICE

HD-tDCS treatments (5 active and 5 sham)

Sham HD-tDCS treatments

Intervention Type DEVICE

HD-tDCS treatments (5 active and 5 sham)

Neuroimaging EEG/fMRI (Aim 3)

Intervention Type DIAGNOSTIC_TEST

This will be done to monitor areas of the brain that are involved in thinking and processing pain. The scanner stimulates the brain to send out signals that will be recorded and analyzed. Additionally, during the MRI the participants brain's electrical activity with will be measured with an EEG machine for part of the MRI. About halfway through the scan, participants will have the EEG equipment removed and then (for participants prior to January 2025) will return to the fMRI scanner for a few additional scans.

Interventions

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EEG

EEG with QST (evoked Pain and Visual Stimulation Assessment)

Intervention Type DIAGNOSTIC_TEST

Neuroimaging EEG/fMRI (Aim 1)

This will be done to monitor areas of the brain that are involved in thinking and processing pain. The scanner stimulates the brain to send out signals that will be recorded and analyzed. Additionally, during the MRI the participants brain's electrical activity with will be measured with an EEG machine for part of the MRI. About halfway through the scan, participants will have the EEG equipment removed and then will return to the fMRI scanner for a few additional scans.

Intervention Type DIAGNOSTIC_TEST

HD-tDCS treatments

HD-tDCS treatments (5 active and 5 sham)

Intervention Type DEVICE

Sham HD-tDCS treatments

HD-tDCS treatments (5 active and 5 sham)

Intervention Type DEVICE

Neuroimaging EEG/fMRI (Aim 3)

This will be done to monitor areas of the brain that are involved in thinking and processing pain. The scanner stimulates the brain to send out signals that will be recorded and analyzed. Additionally, during the MRI the participants brain's electrical activity with will be measured with an EEG machine for part of the MRI. About halfway through the scan, participants will have the EEG equipment removed and then (for participants prior to January 2025) will return to the fMRI scanner for a few additional scans.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

* Satisfy the American College of Rheumatology (2011) survey criteria for the classification of Fibromyalgia (FM).
* Continued presence of pain for more than 50% of days for the past month.
* Mean recalled pain over the last seven days (7-day recall) greater than or equal to 3 on a 10 centimeter (cm) Visual Analog Scale (VAS) for pain; 7-day recall
* Willing to limit the introduction of any new medications or treatment modalities for control of FM symptoms during the study.
* Right-handed.
* Able to travel to the study site to receive (HD-tDCS) treatments five times weekly
* Understanding and willing to complete all study procedures.
* Capable of giving written informed consent.


* Right-handed
* Pain less than 0.5cm on a 10cm Visual Analog Scale (VAS) for pain; 7-day recall
* Understanding and willing to complete all study procedures
* Capable of giving written informed consent

Exclusion Criteria

* Presence of a concurrent autoimmune or inflammatory disease such as rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, et cetera (etc.) that causes pain.
* History of head injury with substantial loss of consciousness
* Peripheral neuropathy of known cause that interferes with activities of daily living.
* Routine daily use of opioid analgesics, marijuana, or history of substance abuse.
* Stimulant medications, such as those used to treat attention-deficit/hyperactivity disorder (ADHD)/Attention deficit disorder (ADD) (for example (e.g.), amphetamine/ dextroamphetamine \[Adderall®\], methylphenidate, dextroamphetamine), or the fatigue associated with sleep apnea or shift work (e.g., modafinil), are excluded.
* Concurrent participation in other therapeutic trials.
* Use of as needed (PRN) over the counter (OTC) pain medications (Nonsteroidal anti-inflammatory drugs (NSAIDs), etc.) on day of electroencephalogram (EEG)/Magnetic resonance imaging (MRI).
* Use of PRN opioid analgesics 48 hours prior to EEG/MRI scan.
* Pregnant or nursing. A pregnancy test will be given prior to EEG/MRI sessions.
* Severe psychiatric illnesses (current schizophrenia, major depression with suicidal ideation, substance abuse within two years)
* Contraindications to EEG/MRI or HD-tDCS methods. These may include but are not limited to: surgical clips, surgical staples, metal implants, and certain metallic dental material.
* Any impairment, activity or situation that in the judgment of the Study Coordinator or Principal Investigators that would prevent satisfactory completion of the study protocol. This includes unreliable, or inconsistent pain scores as deemed by the principal investigator.
* Sufficient knowledge of HD-tDCS techniques to prevent "blinding" of the patient to the study interventions (including significant previous tDCS or HD-tDCS treatment)
* Presence of factors that may preclude the safe use of HD-tDCS
* History vascular surgery in lower limbs or current lower limb vascular dysfunction.
* Subjects with Worker's Compensation, Workman's Compensation, civil litigation or disability claims pertinent to the subject's fibromyalgia; current involvement in out-of-court settlements for claims pertinent to the subject's fibromyalgia; or currently receiving monetary compensation as a result of any of the above.
* Inability or unwillingness of individual to give written informed consent.


* Have met the American College of Rheumatology (2011) survey criteria for the classification of FM.
* Have any chronic medical illness including psychiatric disorders (psychosis, schizophrenia, delusional disorder, etc). (self-reported)
* History of head injury with substantial loss of consciousness
* Peripheral neuropathy of known cause that interferes with activities of daily living
* Routine daily use of opioid analgesics, marijuana or history of substance abuse
* Stimulant medications, such as those used to treat ADD/ADHD (e.g., amphetamine/ dextroamphetamine \[Adderall®\], methylphenidate, dextroamphetamine), or the fatigue associated with sleep apnea or shift work (e.g., modafinil), are excluded.
* Concurrent participation in other therapeutic trials.
* Pregnant or nursing. A pregnancy test will be given prior to EEG/MRI sessions.
* Contraindications for EEG or MRI.
* Use of PRN over the counter (OTC) pain medications (NSAIDs, etc.) on day of MRI scan.
* Use of PRN opioid analgesics 48 hours prior to MRI scan.
* Active substance disorder in the past 24 months, as determined by subject self-report.
* History vascular surgery in lower limbs or current lower limb vascular dysfunction.
* Any impairment, activity or situation that in the judgment of the Study Coordinator or Principal Investigators that would prevent satisfactory completion of the study protocol.
* Inability or unwillingness of individual to give written informed consent.
Minimum Eligible Age

19 Years

Maximum Eligible Age

74 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Center for Complementary and Integrative Health (NCCIH)

NIH

Sponsor Role collaborator

University of Michigan

OTHER

Sponsor Role lead

Responsible Party

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Alexandre DaSilva, DDS, DMedSc

Professor of Dentistry

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Alexandre Dasilva, DDs,DMedsc

Role: PRINCIPAL_INVESTIGATOR

University of Michigan

Locations

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University of Michigan

Ann Arbor, Michigan, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Alanna Harris

Role: CONTACT

Phone: 734-998-6839

Email: [email protected]

Alexandre Dasilva, DDs,DMedSc

Role: CONTACT

Phone: 734-763-5280

Email: [email protected]

Facility Contacts

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Alanna Harris

Role: primary

Other Identifiers

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1R01AT010060-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

HUM00180975

Identifier Type: -

Identifier Source: org_study_id