Personalized Repetitive Transcranial Magnetic Stimulation Treatment for Major Depressive Episode

NCT05465928 | Completed

• 1 other identifier: 81725005-2
• Study Type: interventional
• Target: 219
• Locations: 1 country
• Sites: 1

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.

Conditions

Major Depressive Episode

Keywords

Repetitive Transcranial Magnetic Stimulation; Major Depressive Episode; Functional Magnetic Resonance Imaging

Outcome Measures

Primary Outcomes (3)

• Change from baseline in depressive symptoms assessed by Hamilton depression rating scale 17 items (HAMD-17) at 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.

  Baseline, week 1 and week 2.

• 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.

  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.

  Baseline, week 1 and week 2.

• Change from baseline in neurocognitive function using Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) test at 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.

  Baseline and week 2.

Secondary Outcomes (2)

• Change from baseline in the Clinical Global Impression-Severity scale (CGI-S) at week 1 and week 2.

  Baseline, week 1 and week 2.

• Change from baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) at week 1 and week 2.

  Baseline, week 1 and week 2.

Study Arms (2)

Personalized rTMS

EXPERIMENTAL

The active arm will receive the personalized rTMS treatment with parameters as follows: 1. Neuroimaging biomarker-guided personalized selection for stimulation frequency: low frequency(1HZ) or high frequency (10HZ); 2. Neuroimaging biomarker-guided personalized selection for stimulation site: dorsalmedial prefrontal cortex or occipital cortex; 3. Schedule: 2 sessions per day, five days per week for a total of 20 sessions over 2 weeks.

Device: Active rTMS

sham stimulation rTMS

SHAM COMPARATOR

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

Device: Sham rTMS

Interventions

Active rTMS DEVICE

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.

Also known as: VISHEE Magneuro stimulator

Personalized rTMS

Sham rTMS DEVICE

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.

sham stimulation rTMS

Eligibility Criteria

• Age: 13 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Jiangsu Province Nanjing Brain Hospital: lead

Study Sites (1)

Affiliated Nanjing Brain Hospital, Nanjing Medical University

Nanjing, Jiangsu, 210000, China

Location

Related Publications (10)

• Kalin NH. Advances in Understanding and Treating Mood Disorders. Am J Psychiatry. 2020 Aug 1;177(8):647-650. doi: 10.1176/appi.ajp.2020.20060877. No abstract available.

  PMID: 32741277 BACKGROUND

• Nesvag R, Bramness JG, Handal M, Hartz I, Hjellvik V, Skurtveit S. The incidence, psychiatric co-morbidity and pharmacological treatment of severe mental disorders in children and adolescents. Eur Psychiatry. 2018 Mar;49:16-22. doi: 10.1016/j.eurpsy.2017.12.009. Epub 2018 Feb 3.

  PMID: 29366845 BACKGROUND

• Rumi DO, Gattaz WF, Rigonatti SP, Rosa MA, Fregni F, Rosa MO, Mansur C, Myczkowski ML, Moreno RA, Marcolin MA. Transcranial magnetic stimulation accelerates the antidepressant effect of amitriptyline in severe depression: a double-blind placebo-controlled study. Biol Psychiatry. 2005 Jan 15;57(2):162-6. doi: 10.1016/j.biopsych.2004.10.029.

  PMID: 15652875 BACKGROUND

• Rosenich E, Gill S, Clarke P, Paterson T, Hahn L, Galletly C. Does rTMS reduce depressive symptoms in young people who have not responded to antidepressants? Early Interv Psychiatry. 2019 Oct;13(5):1129-1135. doi: 10.1111/eip.12743. Epub 2018 Oct 10.

  PMID: 30303308 BACKGROUND

• Mayer G, Aviram S, Walter G, Levkovitz Y, Bloch Y. Long-term follow-up of adolescents with resistant depression treated with repetitive transcranial magnetic stimulation. J ECT. 2012 Jun;28(2):84-6. doi: 10.1097/YCT.0b013e318238f01a.

  PMID: 22531199 BACKGROUND

• Hett D, Rogers J, Humpston C, Marwaha S. Repetitive Transcranial Magnetic Stimulation (rTMS) for the Treatment of Depression in Adolescence: A Systematic Review. J Affect Disord. 2021 Jan 1;278:460-469. doi: 10.1016/j.jad.2020.09.058. Epub 2020 Sep 15.

  PMID: 33011525 BACKGROUND

• Weigand A, Horn A, Caballero R, Cooke D, Stern AP, Taylor SF, Press D, Pascual-Leone A, Fox MD. Prospective Validation That Subgenual Connectivity Predicts Antidepressant Efficacy of Transcranial Magnetic Stimulation Sites. Biol Psychiatry. 2018 Jul 1;84(1):28-37. doi: 10.1016/j.biopsych.2017.10.028. Epub 2017 Nov 10.

  PMID: 29274805 BACKGROUND

• Fox MD, Buckner RL, White MP, Greicius MD, Pascual-Leone A. Efficacy of transcranial magnetic stimulation targets for depression is related to intrinsic functional connectivity with the subgenual cingulate. Biol Psychiatry. 2012 Oct 1;72(7):595-603. doi: 10.1016/j.biopsych.2012.04.028. Epub 2012 Jun 1.

  PMID: 22658708 BACKGROUND

• Downar J, Geraci J, Salomons TV, Dunlop K, Wheeler S, McAndrews MP, Bakker N, Blumberger DM, Daskalakis ZJ, Kennedy SH, Flint AJ, Giacobbe P. Anhedonia and reward-circuit connectivity distinguish nonresponders from responders to dorsomedial prefrontal repetitive transcranial magnetic stimulation in major depression. Biol Psychiatry. 2014 Aug 1;76(3):176-85. doi: 10.1016/j.biopsych.2013.10.026. Epub 2013 Nov 28.

  PMID: 24388670 BACKGROUND

• Chang M, Womer FY, Gong X, Chen X, Tang L, Feng R, Dong S, Duan J, Chen Y, Zhang R, Wang Y, Ren S, Wang Y, Kang J, Yin Z, Wei Y, Wei S, Jiang X, Xu K, Cao B, Zhang Y, Zhang W, Tang Y, Zhang X, Wang F. Identifying and validating subtypes within major psychiatric disorders based on frontal-posterior functional imbalance via deep learning. Mol Psychiatry. 2021 Jul;26(7):2991-3002. doi: 10.1038/s41380-020-00892-3. Epub 2020 Oct 1.

  PMID: 33005028 BACKGROUND

Related Links

• Depression

Study Officials

• Fei Wang

  Affiliated Nanjing Brain Hospital, Nanjing Medical University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2022
• First Posted: July 20, 2022
• Study Start: August 2, 2022
• Primary Completion: January 20, 2024
• Study Completion: January 20, 2024
• Last Updated: March 6, 2025

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)