Pain & Reward Neuromodulation of CNS Circuits

Overview

This pilot feasibility study aims to evaluate transcranial magnetic stimulation (TMS) targeting the prefrontal cortex in patients with fibromyalgia syndrome (FMS). The study will assess preliminary efficacy and mechanisms of central nervous system changes using neuroimaging, behavioral tasks, sensory testing, and neuroimmune markers. Participants will undergo MRI scans, multi-day TMS sessions, and complete questionnaires. The goal is to generate pilot data for future trials on neuromodulation for chronic pain.

Detailed description

This is a study to compare activity in the brains of female adults with chronic pain before and after a new intervention. What the researchers learn by doing this study may help them understand how the brain works and how to develop new and targeted treatments for adults with chronic pain.

Female participants in this study will come to Duke Hospital for up to 6 visits. First, there is an MRI scan visit. Then, there are 4 intervention (TMS) visits, one after the other over 4 days. Next, there is an identical follow up MRI scan visit. Afterwards, there is a one month, three month, and six month follow up that can be completed remotely.

During each of 2 MRI study visits, participants will:

* Have a urine test for drug use (and pregnancy if applicable) * Have a blood draw to measure inflammation and/or genetic testing * Have magnetic resonance imaging (MRI) scans of the brain and spine * Complete behavior tests (participate in games or tasks), sensory tests, and questionnaires

During each of 4 TMS study visits, participants will:

* Have brief transcranial magnetic stimulation (TMS) applied to the head * Complete behavior tests (participate in games or tasks), sensory tests, and questionnaires

Participation is complete once the requested study visits and follow-up questionnaires have been completed.

Interventions

• Device Transcranial Magnetic Stimulation (TMS)
  TMS protocol delivered via MagPro X100 stimulator with figure-8 coil targeting prefrontal cortex.

Primary outcome measures

• Change in Pain Intensity [Time frame: Baseline MRI and post-intervention MRI (approximately 3 weeks)]
• Change in Fatigue [Time frame: Baseline MRI and post-intervention MRI (approximately 3 weeks)]
• Change in FMS-related brain/fibro fog as measured by the Montreal Cognitive Assessment (MoCA) [Time frame: Baseline MRI and post-intervention MRI (approximately 3 weeks)]

Secondary outcome measures (3)

• Change in the brain's response to task stimuli [Time frame: Baseline MRI and post-intervention MRI (approximately 3 weeks)]
• Change in the brain's cortico-striatal circuit functional connectivity [Time frame: Baseline MRI and post-intervention MRI (approximately 3 weeks)]
• Ventral-dorsal spinal cord fMRI-indicated activity [Time frame: Baseline MRI and post-intervention MRI (approximately 3 weeks)]

Eligibility criteria

Inclusions:

• Female and ages 18 +
• Ability to read/understand English and give consent to participate
• Physician diagnosis \& confirmation of primary fibromyalgia syndrome
• Verbal agreement to maintain dose of prescribed medication (if any) constant throughout the study, except exclusion medication and except if there is a medical emergency requiring changes in medication
• If enrolled in psychotherapy, verbal agreement to maintain (not change or stop) the psychotherapy during the study
• Absence of use of opioid medications (during the previous 90 days, and no greater than a 30-day period during lifetime)

Exclusions:

• limited ability to participate fully in behavioral tasks, longitudinal follow-up (e.g., plans to move out-of-state within 3 months)
• MRI contraindication (e.g., metal implants, claustrophobia, pregnant or planning to become pregnant)
• any factors that at the discretion of the investigators would adversely affect the participant or the integrity of the study (e.g., ongoing legal action or disability claim regarding pain, uncontrolled psychiatric disorder, head/neck injury, use of certain medications)
• male \*

TMS-Specific Exclusions:

1\. TMS contraindication (e.g., history of seizures, medications contraindicated for risks/efficacy of TMS procedures)

• current hypomania,
• meets diagnostic criteria for current psychotic disorder, or psychotic features,
• meets diagnostic criteria for Bipolar I disorder,
• meets diagnostic criteria for current alcohol or substance use disorder (moderate and high severity)
• current uncontrolled anorexia or other condition requiring hospitalization,
• current serious medical illness, including current severe migraine headaches,
• changed psychotropic medications in the prior 2 months, or plans to change medication during the study,
• history of seizure except those therapeutically induced by ECT (childhood febrile seizures are acceptable and these subjects may be included in the study), history of epilepsy in self or first degree relatives, stroke, brain surgery, head injury, cranial metal implants, known structural brain lesion, devices that may be affected by TMS (pacemaker, medication pump, cochlear implant, implanted brain stimulator),
• conditions associated with increased intracranial pressure, space occupying brain lesion, transient ischemic attack, cerebral aneurysm, dementia, Parkinson's or Huntington's disease, multiple sclerosis,
• use of investigational drug or devices within 4 weeks of screening,
• cochlear implants,
• pregnancy

• Only females will be enrolled in this study because it focuses on patients who have fibromyalgia which is more prevalent (both diagnosed and self-reported) in females.

Due to the contributions of hormones to the conditions under study in this project, female eligibility in this study will be defined as an individual who is female sex at birth and currently female sex

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Duke University Medical Center — Durham

Identifiers

NCT: NCT07525063 · Pro00118676

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗