Clinical trial NCT06813040: Efficacy of Repetitive Transcranial Magnetic Stimulation in Temporomandibular Disorders.
Official title: Efficacy of Repetitive Transcranial Magnetic Stimulation in Chronic Pain in Patients with Temporomandibular Disorders.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Temporomandibular Joint Disorders
Keywords: Temporomandibular Joint Disorders
TMJ disorders
Lead sponsor: University of Coimbra
Sponsor class: OTHER
First posted: 2025-02-06
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Temporomandibular disorder (TMD) refers to a group of musculoskeletal conditions that affect the temporomandibular joint (TMJ), the masticatory muscles, and the associated structures. It is assumed that 30 to 40% of cases of acute painful TMD becomes chronic. Chronic pain is a significant public health problem, affecting professional and social activities, emotional state, and quality of life. The pathophysiological mechanisms involved in chronic orofacial pain are complex and multifaceted and not yet fully understood. The coexistence of psychological factors associated with vast peripheral and central mechanisms makes chronic orofacial pain treatment a complex challenge. Due to the complexity of chronic TMDs, some patients remain refractory to current therapeutic methods. Thus, several efforts have been made to develop therapies aimed at the treatment of neuroplastic changes induced by chronic pain. In this sense, transcranial stimulation methods appear to be a promising technique. Transcranial Magnetic Stimulation (TMS) is a non-invasive, safe, and approved treatment for clinical use in psychiatric disorders such as depression and chronic pain. Given the above, it is necessary to develop studies to investigate the TMS effectiveness in chronic TMD. This study aims to evaluate the effectiveness of transcranial magnetic stimulation in patients with chronic temporomandibular disorders. An additional objective is to determine possible predictors for treatment success based on the assessment of functional brain connectivity and psychosocial characteristics.

Detailed description: Temporomandibular disorder (TMD) is a generic term used to describe musculoskeletal disorders that affect the temporomandibular joint (TMJ), masticatory muscles, and related structures. TMD comprises two main groups: intra-articular TMD and masticatory muscle disorders. It is noteworthy that each of these groups still contains different diagnoses. Furthermore, masticatory muscle disorders and intra-articular TMD often coexist in the same individual. Such characteristics contribute to the complex diagnosis and treatment of TMDs.

It is estimated that TMD affects 5 to 12% of the population and is considered the second most prevalent musculoskeletal disorder, behind only chronic low back pain. Pain, joint noises, and limitation of mandibular movements are the main signs and symptoms of TMD. TMJ noises and limited jaw movements are often associated with intra-articular TMD. On the other hand, pain is a common symptom in different types of TMD, and it can be localized or diffuse and even as otalgia or headache. It is assumed that 30 to 40% of cases of acute painful TMD becomes chronic. Chronic pain impacts professional and social activities, emotional state, and quality of life. The pathophysiological mechanisms of chronic orofacial pain are complex and multifaceted, and not yet fully understood. In addition, the coexistence of psychological factors associated with the vast number of peripheral and central mechanisms (for example, functional and structural neuroplasticity and, more specifically, peripheral and central sensitization) makes the treatment of chronic orofacial pain a challenge extremely complex.

TMD treatment comprises a wide range of therapeutic modalities. Conservative treatments constitute the first therapeutic option, aiming to reduce joint and muscle overload, control local inflammatory factors, and reduce some risk factors, such as waking bruxism and psychological disorders. However, due to the complexity of chronic TMDs, some patients remain refractory to current therapeutic methods. Thus, several efforts have been made to develop therapies to treat neuroplastic changes associated with chronic pain. In this regard, transcranial stimulation methods appear to be a promising treatment. Transcranial Magnetic Stimulation (TMS) is a non-invasive, safe, and approved method for clinical use in psychiatric disorders and chronic pain. Recent scientific evidence has demonstrated that high-frequency TMS when applied to the motor cortex (M1), presents short-term effectiveness in reducing chronic pain and improving quality of life. A systematic review conducted by Ferreira demonstrated promising results of TMS in orofacial pain.

Eligibility criteria: Inclusion Criteria:

* Individuals of both sexes, literate, aged over 18 years with the diagnosis of muscular and/or joint TMD by the Diagnostic Criteria for Temporomandibular Disorders (DC-TMD).
* Pain duration longer than 6 months.
* Intensity of orofacial pain greater than 5 on the visual analogue scale (VAS).

Exclusion Criteria:

* Volunteers who present verbal communication impairment due to a neurological disorder, a sequel to a previous illness, or a psychiatric condition.
* Pregnant women
* Individuals with any impediment to MRI: having a pacemaker or implantable defibrillator, cochlear implant, ferromagnetic aneurysm clips, electrodes used for deep brain stimulation, ocular implants, Swan-Ganz catheter, orthopedic prostheses or metallic bodies close to the area of interest.
* Individuals with any contraindication for transcranial magnetic stimulation: have focal or generalized encephalopathies, increased intracranial pressure, and severe heart disease; history of head trauma, epilepsy, and individuals with first-degree relatives diagnosed with idiopathic epilepsy; use of drugs that lower the seizure threshold (tricyclic antidepressants and antipsychotics); chronic use of alcohol or epileptogenic drugs.

Primary outcomes:
measure: Pain intensity
timeFrame: Primary outcomes will be assessed before and after all TMS sessions. Follow-up will be carried out one week, two weeks, and 1 month after treatment.
measure: Functional limitation
timeFrame: Primary outcomes will be assessed before and after all TMS sessions. Follow-up will be carried out one week, two weeks, and 1 month after treatment.
Secondary outcomes:
measure: Disability associated with pain
timeFrame: Change from baseline to mid-treatment, immediately after the last simulated or active TMS session, and follow-up will be carried out one week, 15 days and 1 month after the end of treatment.
measure: Depression
timeFrame: Change from baseline to mid-treatment, immediately after the last simulated or active TMS session, and follow-up will be carried out one week, 15 days and 1 month after the end of treatment.
measure: Anxiety
timeFrame: Change from baseline to mid-treatment, immediately after the last simulated or active TMS session, and follow-up will be carried out one week, 15 days and 1 month after the end of treatment.
measure: Central sensitization
timeFrame: hange from baseline to mid-treatment, immediately after the last simulated or active TMS session, and follow-up will be carried out one week, 15 days and 1 month after the end of treatment.
measure: Quality of Life
timeFrame: Change from baseline to mid-treatment, immediately after the last simulated or active TMS session, and follow-up will be carried out one week, 15 days and 1 month after the end of treatment.
measure: Functional connectivity
timeFrame: Change from baseline to one week after the end of treatment.
Other outcomes:
Locations:
city: Coimbra
country: Portugal
facility: University of Coimbra
Study officials:
affiliation: ICNAS - Institute of Nuclear Sciences Applied to Health
name: Miguel Castel-Branco, PhD
role: STUDY_DIRECTOR
affiliation: ICNAS - Institute of Nuclear Sciences Applied to Health
name: Catarina Duarte, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Coimbra
name: Natália Ferreira, PhD
role: PRINCIPAL_INVESTIGATOR
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