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Translational Biomarkers in Accelerated Neuromodulation for Treatment-resistant Depression

ClinicalTrials.gov IDNCT05798143

PhaseNA

Enrollment80

SponsorITAB - Institute for Advanced Biomedical Technologies

Age18 Years – 65 Years

SexALL

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Conditions studied

Treatment Resistant Depression

About this study

Background: 30-50% of patients with Major Depressive Disorder (MDD) do not respond adequately despite two or more antidepressant treatments with proper dosage and timing of administration, configuring a condition of Treatment-Resistant Depression (TRD). Repetitive Transcranial Magnetic Stimulation (rTMS) is a neuromodulation technique that uses a magnetic field to stimulate focal cortical brain regions and it has been approved by the FDA for the treatment of TRD. Accelerated rTMS (arTMS) protocols involve multiple daily sessions of rTMS and they have been shown to be equally effective and safe compared to rTMS protocols, with reduced administration time and potentially faster antidepressant efficacy. Objectives: The main aim of this study is to identify MDD endophenotypes/biotypes predictive of response to accelerated treatment of rTMS to better characterize the clinical correlates of response in patients with TRD. Eligibility: Subjects between 18 and 65 years suffering from TRD in stable psychopharmacological treatment for at least one month. Design: This clinical trial includes three phases: 1) a screening phase; a rTMS continued treatment phase; and a follow-up. In order to be enrolled, participants will be screened with: * Medical history to assess the existence of the inclusion criteria and exclude any medical conditions that could contraindicate treatment with arTMS * Questionnaires After being enrolled, baseline data will be collected. In particular, participants will be administered: * Questionnaires * Functional MRI * Cognitive tasks * Eye examination with Electroretinography (ERG) * Blood sampling * Salivary cortisol sampling Repetitive TMS will be delivered during 5 outpatient treatment days (4 times/die). After treatment patients will be contacted by telephone on a weekly basis for the first 3 weeks, to carry out an assessment of the clinical condition. A follow-up visit, in the clinic, will be carried out after 21 days from the last stimulation (Friday), with the administration of psychometric scales. Blood samples will be taken on the first day of stimulation and the day after the last stimulation. Salivary cortisol sampling will be taken before the start of the stimulation protocol, after the first stimulation day and immediately after the last stimulation session foreseen by the protocol. fMRI will be performed during baseline and at the end of treatment. ERG will be performed before the start of the stimulation protocol…

Interventions

Device: Accelerated Repetitive Transcranial Magnetic Stimulation — rTMS is a non-invasive brain stimulation technique. It will be used a MagPro R30 with the Cool-B-70 figure-of-eight coil (MagVenture, Falun, Denmark).

Primary outcomes

Changes in psychometric test indicator of depression - MADRS (Baseline; each 1 day of treatment ; at 1, 2, 3 and 4 weeks.)
Changes in psychometric test indicator of depression - HAM-D 21 (Baseline; 1 week; 4 weeks)
Changes in neuroplasticity - structural RM and fMRI (physiological parameter) (Baseline; day 6)
Changes in neuroplasticity - DTI (physiological parameter) (Baseline; day 6)
Changes in responsivity of nervous tissue (physiological parameter) (Baseline; 4 weeks)
Rate of genetic polymorphism predictor of treatment response (Baseline; day 6)
Change in BDNF level (physiological parameter) (Baseline; day 6)
Change in pro-BDNF (physiological parameter) (Baseline; day 6)

Eligibility information

Inclusion Criteria: * Current diagnosis of Major Depressive Disorder (MDD), based on the Diagnostic and Statistical Manual of Mental Disorder - Fifth Edition (DSM-5); * Subjects without clinical response to at least two antidepressant treatments administered at adequate dosage and duration during the current episode; * Stable psychopharmacological treatment for at least one month. Exclusion Criteria: * Co-morbidity with organic diseases that could interfere with magnetic stimulation safety (epilepsy, brain lesions or diseases, previous neurosurgery, metal grafts, cardiac devices) based on applied procedure guidelines; * Diagnosis of Substance or Alcohol Use Disorder (DSM-5) in the past 6 months; * Substances of abuse or alcohol acute intoxication or abstinence; * Co-morbidity with significant organic or neurological diseases; * Personal or familiar (1st degree relatives) medical history of seizures; * Significant eye diseases that could interfere with ERG execution; * For female patients: Pregnancy/breastfeeding.

Study locations

ITAB, Chieti, 66100 Italy

Before you participate: Varda Clinical is an independent discovery tool, not the study sponsor or a medical provider. Eligibility can only be determined by the official study team. Discuss potential risks and benefits with a qualified healthcare professional.

Source: ClinicalTrials.gov. Record last refreshed by Varda Clinical: 2026-10-05.