Neurophysiology of Fibromyalgia

NCT06006130 | Completed

• 1 other identifier: 16482
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

Fibromyalgia is a syndrome associated with fatigue and chronic pain, leading to significant physical limitations and impaired quality of life. There are several challenges that complicate the diagnosis and management of fibromyalgia. The etiology is not well defined, as there are several proposed factors that may trigger the genesis of pain in fibromyalgia including physical and/or emotional life stressors, and genetic predispositions involving neuromodulator pathways. Chronic pain in fibromyalgia arises in the absence of tissue pathology, and consequently a lack of consensus on reliable diagnostic criteria. Understanding the neurophysiology of fibromyalgia would aid in the discovery of objective biomarkers for diagnosis. Therefore, the goals of this study are to:

1. 1.Compare the neurophysiological responses in fibromyalgia compared to healthy controls.
2. 2.Determine whether a two-week cTMS protocol will alter pain in individuals with fibromyalgia.

Conditions

Fibromyalgia

Keywords

fibromyalgia; transcranial magnetic stimulation; neuroplasticity; pain

Outcome Measures

Primary Outcomes (2)

• Change in PROMIS-29 v2.0 Profile

  Using numerical rating (0 to 5) to assess the change in seven health domains including physical function, anxiety, depression, fatigue, sleep disturbances, ability to participate in social roles and activities, and pain interference. Each category consists of 4 questions. Also uses a numerical rating to asses pain intensity (0-10).

  Experiment 1: At baseline pre-intervention, Experiment 2: At baseline pre-intervention and 2 weeks post-intervention

• Change in Fibromyalgia impact questionnaire (FIQ)

  This instrument will be used to assess the patients feeling and emotion related to their pain experience.

  Experiment 1: At baseline pre-intervention, Experiment 2: At baseline pre-intervention and 2 weeks post-intervention

Secondary Outcomes (10)

• Change in Pain catastrophizing scale-EN-SF

  Experiment 1: At baseline pre-intervention, Experiment 2: At baseline pre-intervention and 2 weeks post-intervention

• Change in Patient Health Questionnaire-4 (PHQ-4)

  Experiment 1: At baseline pre-intervention, Experiment 2: At baseline pre-intervention and 2 weeks post-intervention

• Change in Short-form Posttraumatic Checklist-5 (Short-form PCL-5)

  Experiment 1: At baseline pre-intervention, Experiment 2: At baseline pre-intervention and 2 weeks post-intervention

• Change in Motor-evoked potentials (MEPs)

  Experiment 1: At baseline pre-intervention and immediately following 1 treatment session, Experiment 2: At baseline pre-intervention and 2 weeks post-intervention

• Change in Short-Interval Intracortical Inhibition (SICI)

  Experiment 1: At baseline pre-intervention and immediately following 1 treatment session, Experiment 2: At baseline pre-intervention and 2 weeks post-intervention

Study Arms (2)

Active cTMS

ACTIVE COMPARATOR

Controlled Pulse Parameter Transcranial Magnetic Stimulation (cTMS) will be delivered at 10 Hz, 2000 pulses targeting the hand representation of the left primary motor cortex. cTMS delivery will require \~11 min to complete. In Experiment 1, this intervention will be performed for 1 session (\~11min). In Experiment 2, this intervention will be performed approximately 5 days per week for 2 weeks. In addition, participants will experience their standard medical care.

Device: Active Controlled Pulse Parameter Transcranial Magnetic Stimulation (cTMS)

Sham cTMS

SHAM COMPARATOR

Sham cTMS will be delivered at as a placebo control. It is important to note that from the participant perspective, the sham stimulation will feel and sound identical to active cTMS. In Experiment 2, this intervention will be performed approximately 5 days per week for 2 weeks. In addition, participants will experience their standard medical care.

Device: Sham Controlled Pulse Parameter Transcranial Magnetic Stimulation (cTMS)

Interventions

Active Controlled Pulse Parameter Transcranial Magnetic Stimulation (cTMS) DEVICE

cTMS is a non-invasive, non-painful procedure used to relieve chronic pain and promote short-term changes. The first dorsal interosseous (FDI) muscle of the left motor cortex will be targeted using neuronavigation software. 2000 pulses will be delivered at 10 Hz stimulation. Stimulation will be delivered at 80% of the resting motor threshold obtained from the right FDI muscle. The delivery of cTMS requires 11 minutes in total.

Active cTMS

Sham Controlled Pulse Parameter Transcranial Magnetic Stimulation (cTMS) DEVICE

A sham coil will be utilized for the sham cTMS condition. It is important to note that from the participant perspective, the sham stimulation will feel and sound identical to active. The location and all other parameters of Sham cTMS will be identical to Active cTMS.

Sham cTMS

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years old

You may not qualify if:

• contraindications to TMS
• chronic pain associated with diagnoses other than fibromyalgia

Sponsors & Collaborators

• McMaster University: lead

Study Sites (1)

McMaster University

Hamilton, Ontario, L8S4L1, Canada

Location

Related Publications (9)

• Obata K, Noguchi K. BDNF in sensory neurons and chronic pain. Neurosci Res. 2006 May;55(1):1-10. doi: 10.1016/j.neures.2006.01.005. Epub 2006 Mar 3.

  PMID: 16516994 BACKGROUND

• Ovrom EA, Mostert KA, Khakhkhar S, McKee DP, Yang P, Her YF. A Comprehensive Review of the Genetic and Epigenetic Contributions to the Development of Fibromyalgia. Biomedicines. 2023 Apr 7;11(4):1119. doi: 10.3390/biomedicines11041119.

  PMID: 37189737 BACKGROUND

• Mhalla A, Baudic S, de Andrade DC, Gautron M, Perrot S, Teixeira MJ, Attal N, Bouhassira D. Long-term maintenance of the analgesic effects of transcranial magnetic stimulation in fibromyalgia. Pain. 2011 Jul;152(7):1478-1485. doi: 10.1016/j.pain.2011.01.034. Epub 2011 Mar 11.

  PMID: 21397400 BACKGROUND

• Chowdhury A, Raza H, Meena YK, Dutta A, Prasad G. An EEG-EMG correlation-based brain-computer interface for hand orthosis supported neuro-rehabilitation. J Neurosci Methods. 2019 Jan 15;312:1-11. doi: 10.1016/j.jneumeth.2018.11.010. Epub 2018 Nov 16.

  PMID: 30452976 BACKGROUND

• Toprak Celenay S, Mete O, Coban O, Oskay D, Erten S. Trunk position sense, postural stability, and spine posture in fibromyalgia. Rheumatol Int. 2019 Dec;39(12):2087-2094. doi: 10.1007/s00296-019-04399-1. Epub 2019 Jul 31.

  PMID: 31367796 BACKGROUND

• Vitterso AD, Halicka M, Buckingham G, Proulx MJ, Bultitude JH. The sensorimotor theory of pathological pain revisited. Neurosci Biobehav Rev. 2022 Aug;139:104735. doi: 10.1016/j.neubiorev.2022.104735. Epub 2022 Jun 12.

  PMID: 35705110 BACKGROUND

• Nakata H, Inui K, Wasaka T, Nishihira Y, Kakigi R. Mechanisms of differences in gating effects on short-and long-latency somatosensory evoked potentials relating to movement. Brain Topogr. 2003 Summer;15(4):211-22. doi: 10.1023/a:1023908707851.

  PMID: 12866825 BACKGROUND

• Melzack R. Evolution of the neuromatrix theory of pain. The Prithvi Raj Lecture: presented at the third World Congress of World Institute of Pain, Barcelona 2004. Pain Pract. 2005 Jun;5(2):85-94. doi: 10.1111/j.1533-2500.2005.05203.x.

  PMID: 17177754 BACKGROUND

• Yunus MB. The role of gender in fibromyalgia syndrome. Curr Rheumatol Rep. 2001 Apr;3(2):128-34. doi: 10.1007/s11926-001-0008-3.

  PMID: 11286669 BACKGROUND

MeSH Terms

Conditions

Fibromyalgia; Pain

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Neuromuscular Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Experiment 1: Outcomes assessor will be blinded to the groups (fibromyalgia vs controls) the data is obtained from Experiment 2: Outcomes assessor and participants will be blinded to the intervention group that participants are allocated to (sham vs real treatment)
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Experiment 1: Response to real intervention compared between fibromyalgia and healthy control group Experiment 2: Fibromyalgia participants allocated to real or sham intervention

Study Record Dates

• First Submitted: July 28, 2023
• First Posted: August 23, 2023
• Study Start: February 1, 2024
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: June 4, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)