Intermittent Theta Burst Stimulation in Fibromyalgia Syndrome

NCT06746922 | Recruiting

• 1 other identifier: 2024-KAEK-23
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Research on repetitive transcranial magnetic stimulation therapy in fibromyalgia syndrome (FMS) is increasing rapidly. High-frequency rTMS administration to FMS patients is reported to restore intracortical facilitation and provide successful pain relief. This finding supports restoration of cortical stimulation as one of the possible mechanisms of action for rTMS. One treatment protocol is intermittent theta burst stimulation (iTBS, a variant of excitatory rTMS). Although there are many treatment protocols, there are few widely accepted treatment schemes in the literature. In fibromyalgia syndrome, there is no study in the literature. It was planned to include at least 30 patients aged 18-65 years who were admitted to İzmir Katip Çelebi University Atatürk Training and Research Hospital Physical Medicine and Rehabilitation Outpatient Clinic or hospitalized in the ward and diagnosed with fibromyalgia syndrome according to the 2016 criteria. This study has a prospective, parallel group, randomized, sham-controlled study design. A total of 30 fibromyalgia patients will be randomized into 2 groups and will receive a total of 10 sessions of transcranial magnetic stimulation to the primary motor cortex with intermittent theta bust stimulation technique or sham application. Patients will continue their current fibromyalgia treatment.Numeric Rating Scale-pain intensity (NRS-pain), revised Fibromyalgia Impact Questionnaire (FIQR), Pain Catastrophizing Scale (PCS), Hospital Depression Anxiety Scale (HADS) will be used in the evaluation of the patients.

Conditions

Fibromyalgia; Transcranial Magnetic Stimulation Repetitive; Pain

Keywords

Fibromyalgia; intermittent theta burst stimulation; pain; Pain Catastrophizing; Revised Fibromyalgia Impact Questionnaire; Hospital Anxiety and Depression Scale

Outcome Measures

Primary Outcomes (1)

• Change from baseline in the Numeric Rating Scale

  The numeric rating scale for pain that is a unidimensional measure of pain intensity in adults, including those with chronic pain.The common format is a horizontal bar or line. Similar to the visual analog scale, the numeric rating scale for pain is anchored by terms describing pain severity extremes. The 11-point numeric scale ranges from 0 representing one pain extreme (e.g. "no pain") to 11 representing the other pain extreme (e.g. "pain as bad as you can imagine" or "worst pain imaginable").

  (1) at the beginning of the treatment (T0), (2) at the 1st week (T1), (3) at the 2nd week (T2), (4) four weeks after the end of the treatment (T3).

Secondary Outcomes (3)

• Change from baseline in the Revised Fibromyalgia Impact Questionnaire

  (1) at the beginning of the treatment (T0), (2) at the 2nd week (T2), (3) four weeks after the end of the treatment (T3).

• Change from baseline in the Pain Catastrophizing Scale

  (1) at the beginning of the treatment (T0), (2) at the 2nd week (T2), (3) four weeks after the end of the treatment (T3).

• Change from baseline in the Hospital Anxiety and Depression Scale

  (1) at the beginning of the treatment (T0), (2) four weeks after the end of the treatment (T3).

Study Arms (2)

Active stimulation group

EXPERIMENTAL

Patients will receive intermittent theta burst stimulation (iTBS) to the primary motor cortex, one session per day for a total of 10 sessions.

Device: Intermittent theta-burst stimulation

Sham stimulation group

SHAM COMPARATOR

Patients will receive sham treatment for one session per day for a total of 10 sessions.

Device: Sham Intermittent theta-burst stimulation

Interventions

Intermittent theta-burst stimulation DEVICE

Neuro-MS/D (Neurosoft) rTMS device will be used for stimulation with an angulated figure-of-eight coil. Neuronavigation system will be used to determine the application site. Before each session, active motor threshold (aMT) will be determined by obtaining a motor evoked potential with an amplitude of \>200μV in the EMG recording of the first dorsal interosseous muscle (FDI), which is slightly contracted (10-20% of maximum contraction) in at least five out of 10 stimuli delivered to the primary motor cortex. The handle will be held at a 45° angle to the sagittal plane, pointing backwards and laterally to create posterior-anterior current flow in the brain. The stimulation parameters are as follows: Parameters: Stimulation type:Burst Stimulus amplitude (% MT): 80 Burst frequency in sequence (Hz):5 Pulse frequency within burst (Hz):50 Number of bursts in the sequence: 10 Number of series:20 Interval between sequences: 8 sec Total time: 3min 47sec Total number of pulses: 600

Active stimulation group

Sham Intermittent theta-burst stimulation DEVICE

In the sham application, the probe of the transcranial magnetic stimulation device will be placed in the vertical position and held perpendicular to the vertex and applied at an ineffective dose so that the patient hears the same sound. In order for the device to produce the same sound and warning sounds as the active application, it will be operated at the lowest operating power of 1 power. In the device operating at this power, there is no possibility of any warning due to the upright position of the probe.

Sham stimulation group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Being between the ages of 18-65
• Being diagnosed with fibromyalgia syndrome (according to 2016 criteria)
• Average pain intensity of NRS ≥ 4/10
• Fibromyalgia treatment was stable for the last 3 months and no treatment change was planned during the study

You may not qualify if:

• Having a clinical condition that would constitute a contraindication for TMS (metallic implant, cardiac pacing, pregnancy, epilepsy, head trauma, history of cranial operation...)
• Presence of malignancy
• Systemic rheumatologic diseases
• Major orthopedic problems limiting activities of daily living (gait disturbance or fracture sequelae limiting joint mobility, prostheses, nerve-tendon injuries)
• Serious neurological diseases (increased intracranial pressure, presence of space-occupying lesions in the brain, history of epilepsy, presence of cerebral aneurysm, Parkinson's disease, Huntington's chorea, multiple sclerosis, history of previous head trauma causing loss of consciousness)
• Alcohol or drug addiction
• History of major depression/personality disorder or psychosis
• Having received TMS treatment before
• Taking benzodiazepine, gabapentin/pregabalin or anticonvulsant medications that have the potential to interfere with intermittent theta burst stimulation treatment or have taken them within the last 4 weeks
• Pregnant or planning pregnancy or breastfeeding

Sponsors & Collaborators

• Izmir Katip Celebi University: lead

Study Sites (1)

Izmir Katip Çelebi University Atatürk Training and Research Hospital

Izmir, Karabaglar, 35290, Turkey (Türkiye)

RECRUITING

Related Publications (14)

• Zhou J, Wang Y, Luo X, Fitzgerald PB, Cash RFH, Fitzgibbon BM, Che X. Revisiting the effects of rTMS over the dorsolateral prefrontal cortex on pain: An updated systematic review and meta-analysis. Brain Stimul. 2024 Jul-Aug;17(4):928-937. doi: 10.1016/j.brs.2024.07.011. Epub 2024 Jul 30.

  PMID: 39089648 RESULT

• Cheng YC, Chen WY, Su MI, Tu YK, Chiu CC, Huang WL. Efficacy of neuromodulation on the treatment of fibromyalgia: A network meta-analysis. Gen Hosp Psychiatry. 2024 Mar-Apr;87:103-123. doi: 10.1016/j.genhosppsych.2024.01.007. Epub 2024 Jan 26.

  PMID: 38382420 RESULT

• Naik A, Bah M, Govande M, Palsgaard P, Dharnipragada R, Shaffer A, Air EL, Cramer SW, Croarkin PE, Arnold PM. Optimal Frequency in Repetitive Transcranial Magnetic Stimulation for the Management of Chronic Pain: A Network Meta-Analysis of Randomized Controlled Trials. World Neurosurg. 2024 Apr;184:e53-e64. doi: 10.1016/j.wneu.2024.01.010. Epub 2024 Jan 6.

  PMID: 38185460 RESULT

• Kankane AK, Pandey AK, Ramesh PM, Agarwal A. Role of Repetitive Transcranial Magnetic Stimulation in Treatment of Fibromyalgia: A Randomized Controlled Trial. Ann Indian Acad Neurol. 2024 Mar-Apr;27(2):158-164. doi: 10.4103/aian.aian_1041_23. Epub 2024 Apr 26.

  PMID: 38751921 RESULT

• Hauser W, Ablin J, Fitzcharles MA, Littlejohn G, Luciano JV, Usui C, Walitt B. Fibromyalgia. Nat Rev Dis Primers. 2015 Aug 13;1:15022. doi: 10.1038/nrdp.2015.22.

  PMID: 27189527 RESULT

• Macfarlane GJ, Kronisch C, Dean LE, Atzeni F, Hauser W, Fluss E, Choy E, Kosek E, Amris K, Branco J, Dincer F, Leino-Arjas P, Longley K, McCarthy GM, Makri S, Perrot S, Sarzi-Puttini P, Taylor A, Jones GT. EULAR revised recommendations for the management of fibromyalgia. Ann Rheum Dis. 2017 Feb;76(2):318-328. doi: 10.1136/annrheumdis-2016-209724. Epub 2016 Jul 4.

  PMID: 27377815 RESULT

• Schweiger V, Martini A, Nizzero M, Bonora E, Del Balzo G, Gottin L, Torroni L, Polati L, Zuliani G, Secchettin E, Polati E. Prevalence of FMS Diagnosis According to ACR 2016 Revised Criteria in a Pain Therapy Centre in Italy: Observational Study. Medicina (Kaunas). 2024 Apr 4;60(4):599. doi: 10.3390/medicina60040599.

  PMID: 38674245 RESULT

• Wolfe F, Clauw DJ, Fitzcharles MA, Goldenberg DL, Hauser W, Katz RL, Mease PJ, Russell AS, Russell IJ, Walitt B. 2016 Revisions to the 2010/2011 fibromyalgia diagnostic criteria. Semin Arthritis Rheum. 2016 Dec;46(3):319-329. doi: 10.1016/j.semarthrit.2016.08.012. Epub 2016 Aug 30.

  PMID: 27916278 RESULT

• Kaltsas G, Tsiveriotis K. Fibromyalgia. 2023 Nov 9. In: Feingold KR, Adler RA, Ahmed SF, Anawalt B, Blackman MR, Chrousos G, Corpas E, de Herder WW, Dhatariya K, Dungan K, Hamilton E, Hofland J, Jan de Beur S, Kalra S, Kaltsas G, Kapoor N, Kim M, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, Laferrere B, Levy M, McGee EA, McLachlan R, Muzumdar R, Purnell J, Rey R, Sahay R, Shah AS, Sperling MA, Stratakis CA, Trence DL, Wilson DP, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from http://www.ncbi.nlm.nih.gov/books/NBK279092/

  PMID: 25905317 RESULT

• Perrot S, Choy E, Petersel D, Ginovker A, Kramer E. Survey of physician experiences and perceptions about the diagnosis and treatment of fibromyalgia. BMC Health Serv Res. 2012 Oct 10;12:356. doi: 10.1186/1472-6963-12-356.

  PMID: 23051101 RESULT

• Marques AP, Santo ASDE, Berssaneti AA, Matsutani LA, Yuan SLK. Prevalence of fibromyalgia: literature review update. Rev Bras Reumatol Engl Ed. 2017 Jul-Aug;57(4):356-363. doi: 10.1016/j.rbre.2017.01.005. Epub 2017 Feb 8. English, Portuguese.

  PMID: 28743363 RESULT

• Galvez-Sanchez CM, Reyes Del Paso GA. Diagnostic Criteria for Fibromyalgia: Critical Review and Future Perspectives. J Clin Med. 2020 Apr 23;9(4):1219. doi: 10.3390/jcm9041219.

  PMID: 32340369 RESULT

• Garip Y, Öztaş D, Güler T. Türk geriatrik popülasyonunda fibromiyaljinin yaygınlığı ve yaşam kalitesine etkisi. Ağrı. 2016; 28 :165-170.

  RESULT

• Kia S, Choy E. Update on Treatment Guideline in Fibromyalgia Syndrome with Focus on Pharmacology. Biomedicines. 2017 May 8;5(2):20. doi: 10.3390/biomedicines5020020.

  PMID: 28536363 RESULT

MeSH Terms

Conditions

Fibromyalgia; Pain; Depression

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Ayhan ASKIN, Professor

CONTACT

902322444444; ayhan.askin@ikc.edu.tr

Ezgi Ayan, MD

CONTACT

902322444444; ezgiugurlu45@icloud.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 18, 2024
• First Posted: December 24, 2024
• Study Start: March 13, 2025
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): April 1, 2027
• Last Updated: March 18, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

TU (1)