Explosive Synchronization of Brain Network Activity in Chronic Pain
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- Aim 1 - Brain EEG metric of ES obtained at Visit 1: Correlation between EEG alpha band degree and frequency.
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 19 Years 至 74 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •For Fibromyalgia Participants:
- •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.
- •Inclusion Criteria for Healthy Control Participants:
- •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
排除标准
- •for Fibromyalgia Participants:
- •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.
- •Exclusion Criteria for Healthy Control Participants:
- •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.
研究组 & 干预措施
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.
干预措施: Sham HD-tDCS treatments (Device)
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.
干预措施: EEG (Diagnostic Test)
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.
干预措施: Neuroimaging EEG/fMRI (Aim 1) (Diagnostic Test)
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.
干预措施: EEG (Diagnostic Test)
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.
干预措施: Neuroimaging EEG/fMRI (Aim 1) (Diagnostic Test)
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.
干预措施: EEG (Diagnostic Test)
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.
干预措施: HD-tDCS treatments (Device)
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.
干预措施: Sham HD-tDCS treatments (Device)
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.
干预措施: Neuroimaging EEG/fMRI (Aim 3) (Diagnostic Test)
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.
干预措施: EEG (Diagnostic Test)
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.
干预措施: HD-tDCS treatments (Device)
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.
干预措施: Neuroimaging EEG/fMRI (Aim 3) (Diagnostic Test)
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.
干预措施: EEG (Diagnostic Test)
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.
干预措施: HD-tDCS treatments (Device)
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.
干预措施: Sham HD-tDCS treatments (Device)
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.
干预措施: Neuroimaging EEG/fMRI (Aim 3) (Diagnostic Test)
结局指标
主要结局
Aim 1 - Brain EEG metric of ES obtained at Visit 1: Correlation between EEG alpha band degree and frequency.
时间窗: 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.
时间窗: 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.
次要结局
- Aim 1: Resting brain functional connectivity using functional magnetic resonance imaging obtained at Visit 2(Visit 2 (days 0-3))
- Aim 1: Insular Glx (glutamate + glutamine) using proton magnetic resonance spectroscopy obtained at Visit 2(Visit 2 (days 0-3))
研究者
Alexandre DaSilva, DDS, DMedSc
Professor of Dentistry
University of Michigan