PRTMSTMDEAYA: Personalized Repetitive Transcranial Magnetic Stimulation Treatment for Major Depressive Episode

Sponsor

Jiangsu Province Nanjing Brain Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT05465928

Collaborator

(none)

120

Enrollment

Location

Arms

Anticipated Duration (Months)

7.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Adolescents and young adults with mood disorders experiencing major depressive episode have poor efficacy of medication treatment. Repetitive magnetic transcranial stimulation (rTMS) has been proven adjuvant efficacy in patients with major depressive episode. However, the optimal evidence-based stimulation parameters have not been clearly defined, which greatly limits the efficacy of rTMS in the treatment of major depressive episode.

This trial will compare a novel form of personalized rTMS treatment protocol guided by neuroimaging biomarkers to the sham stimulation.The personalized selection of stimulation parameters, such as stimulation site, frequency and magnetic pulse number, will be determined by neuroimaging biomarkers.

The study aims to propose a novel personalized neuroimaging-guided rTMS strategy, to evaluate the efficacy and safety of the treatment, further to understand the biological mechanism of the personalized rTMS treatment.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Episode	Device: Active rTMS Device: Sham rTMS	N/A

Detailed Description

Mood disorders, including mainly bipolar disorder (BD) and major depressive disorder (MDD), have become the primary health problem and one of the leading causes of functional disability in adolescents and young adults. In China, the incidence of mood disorders such as BD and MDD in adolescents and young adults has increased rapidly in recent years. Particularly, mood disorder patients currently experiencing major depressive episode are considered to be at high risk for suicide, and pharmacological treatment showed poor efficacy to such depressive patients. Mood disorders with major depressive episode have become one of the main threats to youth mental health in China. Therefore, it is of great significance to explore a series of early intervention strategies for adolescents and young adults with major depressive episode.

rTMS is a non-invasive brain stimulation treatment strategy with mild side effects. In 2008, rTMS was approved by the Food and Drug Administration (FDA) for the treatment of major depression. The selection of stimulation parameters often has a vital impact on the clinical efficacy of rTMS treatment. Several clinical trials have reported the efficacy and safety of rTMS on treatment resistant major depression. However, the evidence-based optimal targets and other stimulation parameters have not been clearly defined, which greatly limits the efficacy of rTMS in the treatment of major depressive episode. To date, there is no large randomized clinical trial (RCT) exploring an optimization of rTMS on adolescents and young adults with major depressive episode.

This study is a double-blind randomized controlled trial aiming at assessing the efficacy and safety of a novel personalized rTMS treatment protocol compared to sham stimulation for major depressive episode in adolescents and young adults with mood disorders. Participants will be assigned randomly (1:1) to the personalized rTMS group or the sham stimulation group. Participants in the rTMS group will be treated with 20 sessions (2 sessions per day) of personalized rTMS treatment, and participants in the sham stimulation group will receive the same scheme of rTMS treatment but with sham coil. The selection of stimulation parameters (stimulation site, frequency, number of pulses, number of sessions, train and inter-train duration) in both groups will be based on neuroimaging biomarkers extracted via machine learning method. Participants in both groups will maintain the stable drug regimen during the rTMS trial.

At baseline and after each 10 sessions of treatment, patients will receive the assessment of depressive symptom severity, cranial magnetic resonance imaging (MRI) scan and peripheral blood collection (about 15ml peripheral blood). Before and after 20 sessions of treatment, neurocognitive function test will be performed. The purposes of the present study are to: 1) evaluate the clinical response to the personalized rTMS treatment by comparing the change in depressive symptom and neurocognitive function over the course of rTMS trial. 2) further understand the possible biological mechanism underlying the efficacy of personalized rTMS treatment by analyzing alterations from multidimensional data of neuroimaging, plasma proteomics and metabolomics.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Neuroimaging Biomarker-Guided Personalized Repetitive Transcranial Magnetic Stimulation (rTMS) Treatment for Major Depressive Episode in Adolescents and Young Adults With Mood Disorders: A Randomized, Double-Blind, Controlled Study

Actual Study Start Date :

Aug 1, 2022

Anticipated Primary Completion Date :

Dec 31, 2023

Anticipated Study Completion Date :

Dec 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Personalized rTMS The active arm will receive the personalized rTMS treatment with parameters as follows: Neuroimaging biomarker-guided personalized selection for stimulation frequency: low frequency(1HZ) or high frequency (10HZ); Neuroimaging biomarker-guided personalized selection for stimulation site: dorsalmedial prefrontal cortex or occipital cortex; Schedule: 2 sessions per day, five days per week for a total of 20 sessions over 2 weeks.	Device: Active rTMS rTMS is a non-invasive neuromodulation therapy which has been recognized as a helpful treatment for depression. During each rTMS treatment, the magnetic field is generated by a coil which is placed on the head near the brain region of interest, and further, an electrical current is induced to modulate brain activity. Other Names: VISHEE Magneuro stimulator
Sham Comparator: sham stimulation rTMS Sham stimulation arm will receive the same scheme of rTMS but with a sham coil.	Device: Sham rTMS The sham rTMS stimulation is performed based on a sham coil which will mimic scalp sensations and the acoustic artifact of the active stimulation, without delivering any magnetic pulse.

Arm

Intervention/Treatment

Experimental: Personalized rTMS

The active arm will receive the personalized rTMS treatment with parameters as follows: Neuroimaging biomarker-guided personalized selection for stimulation frequency: low frequency(1HZ) or high frequency (10HZ); Neuroimaging biomarker-guided personalized selection for stimulation site: dorsalmedial prefrontal cortex or occipital cortex; Schedule: 2 sessions per day, five days per week for a total of 20 sessions over 2 weeks.

Device: Active rTMS

rTMS is a non-invasive neuromodulation therapy which has been recognized as a helpful treatment for depression. During each rTMS treatment, the magnetic field is generated by a coil which is placed on the head near the brain region of interest, and further, an electrical current is induced to modulate brain activity.

Other Names:

VISHEE Magneuro stimulator

Sham Comparator: sham stimulation rTMS

Sham stimulation arm will receive the same scheme of rTMS but with a sham coil.

Device: Sham rTMS

The sham rTMS stimulation is performed based on a sham coil which will mimic scalp sensations and the acoustic artifact of the active stimulation, without delivering any magnetic pulse.

Outcome Measures

Primary Outcome Measures

Change from baseline in depressive symptoms assessed by Hamilton depression rating scale 17 items (HAMD-17) at week 1 and week 2. [Baseline, week 1 and week 2.]
The HAMD-17 scale has 17 items. The total score ranges from 0-52, with higher score indicating more severe depressive symptoms. A total score of 0-7 is considered to be normal. Scores of 17 or higher indicate moderate, severe, or very severe depression.
Change from baseline in neurocognitive function using Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) test at week 2. [Baseline and week 2.]
RBANS is a test for identifying and characterizing abnormal cognitive decline for patients with neuropsychiatric disorders. The RBANS is comprised of five domains, which are Immediate Memory, Visuospatial /Constructional, Language, Attention and Delayed Memory. The total score of RBANS range from 40-160, with 160 referring to higher cognitive functioning. A score of 95-115 is in the average range; score of 70-85 mild to moderate cognitive impairment; score <70 moderate to severe impairment.
Change from baseline in the amplitude of low-frequency fluctuation (ALFF) values measured by resting-state functional magnetic resonance imaging (fMRI) at week 1 and week 2. [Baseline, week 1 and week 2.]
Participants will undergo fMRI scans prior to beginning rTMS treatment (week 0) and after completing 10 sessions of rTMS treatment (weeks 1) and after completing 20 sessions of rTMS treatment (weeks 2). ALFF is a fMRI indicator that reflects the spontaneous neural activity. After data acquisition, whole-brain voxel-wise analysis of ALFF values will be performed to detect the change from baseline in brain functional activity at week 1 and week 2.

Secondary Outcome Measures

Change from baseline in the Clinical Global Impression-Severity scale (CGI-S) at week 1 and week 2. [Baseline, week 1 and week 2.]
The CGI-S is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. A rating of 1 is considered normal, or with the least severe symptoms, a rating of 7 is extremely ill, or the worst symptoms.
Change from baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) at week 1 and week 2. [Baseline, week 1 and week 2.]
MADRS is a clinician-rated scale used to assess depressive symptom severity and detect changes due to antidepressant treatment. The scale consists of 10 items, each of which is rated from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms). The total score of MADRS ranges from 0 to 60, with higher score indicating more severe depression.

Eligibility Criteria

Criteria

Ages Eligible for Study:

13 Years to 25 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Between 13 and 25 years of age;
Participants fulfill the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) diagnostic criteria for major depressive disorder (MDD) or bipolar disorder (BD). Participants are assessed by the Structured Clinical Interview for DSM-IV for Axis I Disorders (SCID-I, patients' age ≥18 years old), or the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version (K- SADS-PL, patients' age< 18 years old);
A current moderate or severe depressive episode defined by HAMD≥17 and Young Mania Rating Scale (YMRS) <12;
Participants receive a stable psychotropic medication regimen prior to randomization to the trial and are willing to remain on the stable regimen during the rTMS treatment phase;
Participants and 1 or 2 parents (patients' age< 18 years old) provide informed consent after the detailed description of the study.

Exclusion Criteria:

Prior rTMS or electroconvulsive therapy (ECT) treatment or standard psychological therapy within 6 months prior to screening;
Comorbidity of other DSM-IV axis I disorders or personality disorders;
Judged clinically to be at serious suicidal risk;
Diabetes mellitus, hypertension, vascular and infectious diseases and other major medical comorbidities;
Unstable medical conditions, e.g., severe asthma;
Neurological disorders, e.g., history of head injury with loss of consciousness for ≥ five minutes, cerebrovascular diseases, brain tumors and neurodegenerative diseases;
Mental retardation or autism spectrum disorder;
Contraindications to MRI (e.g., severe claustrophobia, pacemakers, metal implants);
Contraindications to rTMS (e.g., metal in head, history of seizure, electroencephalogram (EEG) test suggesting high risk of seizure, known brain lesion);
Current drug/alcohol abuse or dependence;
Pregnant or lactating female.