Pain & Reward Neuromodulation of CNS Circuits (PRANCIR)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Fibromyalgia; Fibromyalgia Syndrome; Chronic Pain and Fatigue
• Intervention / Treatment: Device: Transcranial Magnetic Stimulation (TMS)

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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Martucci Lab Clinical Research Specialist; Phone Number: 919-684-3161; Email: ChronicPainResearch@duke.edu
• Study Contact Backup: Name: Darius Williams; Phone Number: 919-684-2758; Email: ladarius.williams@duke.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusions:

1. Female and ages 18 +
2. Ability to read/understand English and give consent to participate
3. Physician diagnosis & confirmation of primary fibromyalgia syndrome
4. 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
5. If enrolled in psychotherapy, verbal agreement to maintain (not change or stop) the psychotherapy during the study
6. Absence of use of opioid medications (during the previous 90 days, and no greater than a 30-day period during lifetime)

Exclusions:

1. limited ability to participate fully in behavioral tasks, longitudinal follow-up (e.g., plans to move out-of-state within 3 months)
2. MRI contraindication (e.g., metal implants, claustrophobia, pregnant or planning to become pregnant)
3. 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)
4. male *

TMS-Specific Exclusions:

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

1. current hypomania,
2. meets diagnostic criteria for current psychotic disorder, or psychotic features,
3. meets diagnostic criteria for Bipolar I disorder,
4. meets diagnostic criteria for current alcohol or substance use disorder (moderate and high severity)
5. current uncontrolled anorexia or other condition requiring hospitalization,
6. current serious medical illness, including current severe migraine headaches,
7. changed psychotropic medications in the prior 2 months, or plans to change medication during the study,
8. 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),
9. conditions associated with increased intracranial pressure, space occupying brain lesion, transient ischemic attack, cerebral aneurysm, dementia, Parkinson's or Huntington's disease, multiple sclerosis,
10. use of investigational drug or devices within 4 weeks of screening,
11. cochlear implants,

12. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active TMS; Participants receive TMS over 4 consecutive days (20 sessions total).	Device: Transcranial Magnetic Stimulation (TMS); TMS protocol delivered via MagPro X100 stimulator with figure-8 coil targeting prefrontal cortex.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Pain Intensity	PROMIS Short Form - Pain Intensity (3a) is a 3-item measure which includes questions of pain at its worst (past 7 days), average pain (past 7 days), and pain right now (at time of survey). Each item is rated from No Pain (1) to Very Severe (5).	Baseline MRI and post-intervention MRI (approximately 3 weeks)
Change in Fatigue	The PROMIS Fatigue Computer Adaptive Test (CAT) is a dynamic, patient-reported outcome tool that measures fatigue severity (intensity, frequency, and impact) over the past seven days. Using item response theory (IRT), it selects the next best question based on previous answers, typically requiring only 4-6 items to produce highly precise, reliable scores while minimizing patient burden. Scoring: Results are reported as T-scores, where 50 is the general population mean and 10 is the standard deviation. A T-score of 60 or higher is one standard deviation worse than average.	Baseline MRI and post-intervention MRI (approximately 3 weeks)
Change in FMS-related brain/fibro fog as measured by the Montreal Cognitive Assessment (MoCA)	The Montreal Cognitive Assessment (MoCA) is a valid, 30-point screening tool used to assess "fibro fog"-the cognitive dysfunction, memory loss, and attention difficulties associated with fibromyalgia. Scoring: The test is scored out of 30 points. A score of 26-30 is considered normal, while scores below 26 may indicate mild cognitive impairment (19-25) or more advanced impairment (below 21). One point is added for individuals with 12 years or fewer of formal education.	Baseline MRI and post-intervention MRI (approximately 3 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the brain's response to task stimuli	Functional Magnetic Resonance Imaging (fMRI) will be used to track blood-oxygen-level-dependent (BOLD) signals during reward anticipation and feedback. BOLD signal change identifies neural activity in the brain which will be reported as normalized to percent signal change (Avg%Δ) relative to the mean image intensity to allow for cross-subject comparison (i.e., arbitrary units scale).	Baseline MRI and post-intervention MRI (approximately 3 weeks)
Change in the brain's cortico-striatal circuit functional connectivity	Functional connectivity in fMRI measures the statistical dependencies (similarities) between blood oxygen level-dependent (BOLD) signal time series from different brain regions. Typically quantified using Pearson's correlation or covariance in either resting-state or task-based studies, it identifies synchronized activity indicating functionally linked regions/networks.	Baseline MRI and post-intervention MRI (approximately 3 weeks)
Ventral-dorsal spinal cord fMRI-indicated activity	Amplitude of Low-Frequency Fluctuations (ALFF) in fMRI measures the intensity of spontaneous brain activity by calculating the square root of the power spectrum (via Fast Fourier Transform) within a specific low-frequency range. It quantifies the amplitude of resting-state BOLD signal oscillations, typically after voxel-wise standardization (i.e., arbitrary units scale).	Baseline MRI and post-intervention MRI (approximately 3 weeks)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood cytokine levels	Cytokines in blood, when measured using Meso Scale Discovery (MSD) multiplex immunoassay kits, are typically reported in picograms per milliliter (pg/mL). MSD assays are known for their high sensitivity, capable of detecting analytes in the low pg/mL to sub-pg/mL range.	Baseline MRI and post-intervention MRI (approximately 3 weeks)
PEG Scale Change	The PEG scale (Pain, Enjoyment, General Activity) is a 3-item, patient-reported tool that measures chronic pain intensity and its interference with daily life. It uses a 0-10 numerical rating scale (NRS) for each item, where 0 represents "no pain/no interference" and 10 represents "worst pain/complete interference," averaging the three to produce a final score.	Baseline MRI and post-intervention MRI (approximately 3 weeks)
Fibromyalgia Impact Questionnaire (FIQ-R) Change	The Fibromyalgia Impact Questionnaire (FIQ) and its revision (FIQR) measure the overall impact of fibromyalgia on a patient's life, including physical function, work difficulty, pain, fatigue, sleep quality, and psychological symptoms over the past 7 days. Total scores range from 0 to 100, with higher scores indicating greater severity.	Baseline MRI and post-intervention MRI (approximately 3 weeks)

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: American Fibromyalgia Syndrome Association
• Investigators: Principal Investigator: Katherine T Martucci, PhD, Duke University

Publications and helpful links

Helpful Links

• Martucci Lab Website

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: April 6, 2026
• First Submitted That Met QC Criteria: April 6, 2026
• First Posted (Actual): April 13, 2026

Study Record Updates

• Last Update Posted (Actual): June 3, 2026
• Last Update Submitted That Met QC Criteria: June 1, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: pain; fatigue; Neuromodulation; Transcranial Magnetic Stimulation; Fibromyalgia; Fibromyalgia Syndrome; brain fog; fibro fog; cognitive issues; trouble sleeping; AFSA
• Additional Relevant MeSH Terms: Neurologic Manifestations; Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Mental Disorders; Neuromuscular Diseases; Rheumatic Diseases; Behavioral Symptoms; Sleep Wake Disorders; Pathological Conditions, Signs and Symptoms; Behavior; Signs and Symptoms; Pain; Parasomnias; Fibromyalgia; Chronic Pain; Fatigue; Mental Fatigue; Therapeutics; Magnetic Field Therapy; Transcranial Magnetic Stimulation
• Other Study ID Numbers: Pro00118676

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: As this is a small feasibility trial and will not be published, we do not plan to share the data.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No