Longitudinal Study on the Sustainability of Transcranial Magnetic Stimulation Protocols - Biomarkers

NCT07684911 | Recruiting

• 2 other identifiers: RC25_01_JMB2025-A02833-46
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Despite advances in the effective treatment of major depressive disorder using repetitive transcranial magnetic stimulation (rTMS), the processes that determine a patient's response trajectory remain poorly understood. Currently, there are no validated clinical or neurophysiological markers that can identify factors predicting the durability of the response to rTMS at the individual level. This constitutes a major limitation for planning individualised treatments and highlights the need for precision medicine approaches and reliable biomarkers to predict the long-term efficacy of TMS-based interventions, thereby enabling more informed clinical decisions and optimised resource allocation. rTMS is assumed to work by inducing neuroplasticity on multiple levels of the nervous system, ranging from modulating neurotransmitter release to changing structural and functional brain circuits. While rTMS likely acts as a universal modulator of neuroplasticity, the exact mechanisms are not fully established, especially regarding long-term durability. The LONGISTIM-BIO study ("Longitudinal Study on the Durability of Transcranial Magnetic Stimulation Protocols - Biomarkers") aims to explore the duration of the treatment effect following an initial response to a course of TMS treatment and examines potential neurophysiological and clinical/sociodemographic predictors associated with the trajectories of the treatment effect. More explicitly, it examines neuroplasticity as a biomarker of treatment response durability, and explores its association with heart-brain-coupling (HBC), a physiological marker of rTMS target engagement, as well as inflammation, as measured by a blood test (white blood cells, C-reactive protein (CRP)). During this study, participants undergo an rTMS treatment as per standard clinical care. They receive daily sessions of 20Hz rTMS targeting the left dorsolateral prefrontal cortex during which the heart rate will be recorded. Before the first rTMS session, after the last session, and one month after the last session, the severity of depression is evaluated using both the MADRS and the PHQ-8 questionnaire. At the one-month follow-up, the effectiveness of the course is determined by a 50% improvement in the MADRS score. Following the 1-month follow-up visit, if meeting the inclusion criteria, patients will receive bi-weekly assessments of depression severity (PHQ-8 as primary and MADRS self-rated questionnaire as secondary outcome). If two consecutive PHQ-8 questionnaires are pathological (score ≥10), a new rTMS course is scheduled with the shortest delay possible. During this new course of treatment, participation in the study includes:

• a blood draw prior to the first TMS session
• 4 magnetic resonance imaging (MRI) scans: #1 before the course of treatment, #2 at the end of the course, #3 one month after the end of the treatment, and #4 upon the expected date of relapse. Patients will again be monitored using self-report questionnaires (PHQ-8 and MADRS-SR) every 2 weeks until a relapse occurs.

Conditions

Depression - Major Depressive Disorder; Depression Bipolar; Depression Unipolar

Keywords

Major Depressive Disorder; Depression Bipolar; Repetitive Transcranial Magnetic Stimulation; rTMS; Depression Unipolar; Durability; Neuroplasticity; Inflammation; heart rate

Outcome Measures

Primary Outcomes (1)

• The sustainability of the antidepressant effect of a conventional 20 Hz rTMS course targeting the left left dorsolateral prefrontal cortex.

  The time in weeks before depressive relapse, defined by a score of ≥10 on the 8-item version of the Patient Health Questionnaire (PHQ-8) at two successive evaluations spaced 15 days apart.

  From enrollment until last assessment : 12 months

Secondary Outcomes (7)

• Evaluation of sociodemographic determinants associated with durability.

  From enrollment until last assessment : 12 months

• Evaluation of clinical determinants associated with durability.

  From enrollment until last assessment : 12 months

• Evaluation of therapeutic determinants associated with durability.

  From enrollment until last assessment : 12 months

• Evaluation of neuroplasticity as a surrogate of durability.

  From enrollment until last assessment : 12 months

• Evaluation of heart-brain coupling associated with durability.

  From enrollment until last assessment : 12 months

Study Arms (1)

Patients undergoing rTMS treatment course

Other: Repetitive transcranial magnetic stimulation

Interventions

Repetitive transcranial magnetic stimulation OTHER

Participants receive a conventional 20Hz TMS protocol as per standard clinical care. During the 20Hz protocol, participants receive 10 daily sessions of 20 Hz rTMS (one per day over 2 weeks), each consisting of 75 trains of 40 pulses (2s per train) with a 10 seconds inter-train interval (ITI), totaling 3,000 pulses per session and 30,000 pulses over the full course. The intensity is 120% of the participant's motor threshold (MT).

Patients undergoing rTMS treatment course

Eligibility Criteria

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

Study Population

Patients undergoing a TMS course as part of clinical care at the Adult Psychiatry University Hospital Unit of the Guillaume Régnier Hospital Center.

You may qualify if:

• Patients aged 18 or older.
• Patients who have experienced treatment-resistant unipolar or bipolar depression and responded to a previous TMS course (response defined by a 50% reduction in MADRS score).
• Sufficient command of French to complete questionnaires and follow instructions during MRI assessments and TMS treatments.
• Willingness to comply with all study procedures, including availability for the duration of the study, and to communicate with study staff about adverse events and other clinically relevant information.
• Patients who have expressed their informed written consent to participate in the study.
• Person affiliated with a social welfare scheme or other scheme.
• Current psychiatric comorbidity (suicidal risk, psychotic episode).
• Unstable somatic pathology: active cancer, unstabilized endocrinological pathology, untreated sleep apnea.
• For neuroimaging: Contraindications to magnetic resonance imaging (MRI) such as ferromagnetic metal in the body or severe claustrophobia
• Adults under legal protection (legal guardianship, conservatorship, trusteeship), persons deprived of their liberty
• Pregnancy or breast-feeding.

Sponsors & Collaborators

• Hospital Center Guillaume Régnier: lead

Study Sites (1)

Centre Hospitalier Guillaume Régnier

Rennes, 35700, France

RECRUITING

Related Publications (35)

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MeSH Terms

Conditions

Bipolar Disorder; Depressive Disorder, Major; Inflammation

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders; Depressive Disorder; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Central Study Contacts

Jean-Marie BATAIL

CONTACT

+332 99 33 39 37; jm.batail@ch-guillaumeregnier.fr

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 23, 2026
• First Posted: July 6, 2026
• Study Start: June 4, 2026
• Primary Completion (Estimated): February 1, 2029
• Study Completion (Estimated): August 1, 2029
• Last Updated: July 6, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)