Accelerated Intermittent Theta-Burst Stimulation Ameliorate Major Depressive Disorder by Regulating CAMKII Pathway

NCT05913960 | Recruiting

• 1 other identifier: IITA20230315
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

Major depressive disorder(MDD) is a complex and heterogeneous mental disorder. Repeated transcranial magnetic stimulation (rTMS), as a non-invasive neuroregulatory technique, has shown a promising function in the treatment of depression. Theta-burst transcranial magnetic stimulation (TBS) model significantly shortened the duration of physical therapy treatment, and iTBS under the accelerated model (The latter is referred to as aiTBS)showed promising therapeutic effect. However, whether aiTBS has a better and faster curative effect in the first untreated or recurrent unmedicated MDD patients and the mechanism of its alleviation of depressive symptoms remains unclarified. This project intends to verify changes in CAMKII levels, CAMKII molecules and GABA receptors in brain-derived exosomes in normal controls and patients who received sham, aiTBS and high-frequency (10Hz) stimulation respectively. Neuroimaging and TMS-EEG were used to pinpoint the target of stimulation and to record the changes of brain waves before and after treatment in real time. To clarify the neurobiological mechanism of aiTBS rapidly improving depression, and to provide a new strong evidence for clinical transcranial magnetic stimulation for accurate treatment of MDD patients.

Conditions

Major Depressive Disorder; Major Depressive Disorder, Recurrent

Keywords

major depressive disoerder; first episode without medication; recurrent unmedicated

Outcome Measures

Primary Outcomes (3)

• Hamilton depression scale-24

  Assessement of depressive status,a score of more than 35 May indicate severe depression; More than 20 points, may be mild or moderate depression; A score of less than 8 indicates no symptoms of depression

  baseline

• Hamilton depression scale-24

  Assessement of depressive status,a score of more than 35 May indicate severe depression; More than 20 points, may be mild or moderate depression; A score of less than 8 indicates no symptoms of depression

  5days

• Hamilton depression scale-24

  Assessement of depressive status,a score of more than 35 May indicate severe depression; More than 20 points, may be mild or moderate depression; A score of less than 8 indicates no symptoms of depression

  4 weeks

Secondary Outcomes (13)

• Change in the score of THINC-it.

  Baseline

• Change in the score of THINC-it.

  5 days

• Change in the score of THINC-it.

  4 weeks

• Change in neuroimaging using functional magnetic resonance

  Baseline

• Change in neuroimaging using functional magnetic resonance

  5 days

Study Arms (3)

Placebo stimulation

SHAM COMPARATOR

The sham group of MDD will receive sham rTMS stimulation.

Device: sham stimulation

accelerated intermittent theta burst stimulation

ACTIVE COMPARATOR

Stimulation site: According to the localization of neural orientation navigation system, magnetic resonance data was read in Brainsight software, and three-dimensional brain reconstruction was carried out. The stimulation target was located in the coordinates of Montreal Neurological Institute (MNI), which was located in the left dorsolateral prefrontal cortex BA46(-44, 40, 29).The treatment intensity was 100% exercise threshold, and a TBS stimulus series was stimulated for 2 seconds, including 10 times of 3 intra plexus stimuli of 50Hz and 5Hz intraplexus stimuli, 10s of interval, repeated 60 times, that is, a total of 1800 pulses per treatment, 10 times a day, 50 minutes interval, a total of 18000 pulses per day, continuous for 5 days.

Device: accelerated intermittent theta burst stimulation

high frequency stimulation

ACTIVE COMPARATOR

Stimulation site: According to the localization of neural orientation navigation system, magnetic resonance data was read in Brainsight software, and three-dimensional brain reconstruction was carried out. The stimulation target was located in the coordinates of Montreal Neurological Institute (MNI), which was located in the left dorsolateral prefrontal cortex BA46(-44, 40, 29).Treatment intensity was 100% exercise threshold, continuous 10Hz stimulation, repeated 75 times, that is, 3000 pulses per treatment, 6 times a day, 50 minutes interval, a total of 18000 pulses per day, continuous stimulation for 5 days.

Device: high frequency stimulation

Interventions

sham stimulation DEVICE

The parameters in the sham arm will be as above with the internal randomization of the device internally switching to sham in a blinded fashion.

Placebo stimulation

accelerated intermittent theta burst stimulation DEVICE

Participants in the active stimulation group will receive the accelerated intermittent TBS to left DLPFC. The L-DLPFC will be targeted utilizing the neuronavigation system. Stimulation intensity will be standardized at 90% of RMT. Stimulation will be delivered to the L-DLPFC using an NTK-TMS-II100 TMS device,is compatible with the Brainsight TMS navigation system.

accelerated intermittent theta burst stimulation

high frequency stimulation DEVICE

Participants in the active stimulation group will receive the high frequnency stimulation to left DLPFC. The L-DLPFC will be targeted utilizing the neuronavigation system. Stimulation intensity will be standardized at 90% of RMT. Stimulation will be delivered to the L-DLPFC using an NTK-TMS-II100 TMS device,is compatible with the Brainsight TMS navigation system.

high frequency stimulation

Eligibility Criteria

• Age: 12 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Sign a written informed consent to participate in the trial and receive treatment;
• Major depressive disorder diagnosis;
• Hamilton depression scale (HAMD - 24) 24 total score 20 points or more;
• First episode or recurrence of depression patients, not taking psychiatric drugs;
• The han nationality, right-handed;
• Junior high school or above;

You may not qualify if:

• Other organic mental disorders and mental retardation and other severe mental disorders;
• Infection, trauma, and autoimmune diseases or other possible interference test evaluation of disease;
• Alcohol and drug dependence or is being treated for a hormone drugs patients;
• Craniocerebral injury;
• Seizure or a family history of epilepsy;
• Pregnancy and lactation women;
• All landowners had a metal and MRI contraindications or MRI examination revealed abnormal brain structure.

Sponsors & Collaborators

• First Affiliated Hospital of Zhejiang University: lead

Study Sites (1)

the First Affiliated Hospital,Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Major; Recurrence

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

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

Study Record Dates

• First Submitted: March 16, 2023
• First Posted: June 22, 2023
• Study Start: February 9, 2023
• Primary Completion: March 15, 2024
• Study Completion (Estimated): March 15, 2027
• Last Updated: June 22, 2023

Record last verified: 2023-03

Locations

CN (1)