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

NCT ID: NCT05913960

Last Updated: 2023-06-22

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-02-09
• Study Completion Date: 2027-03-15

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Placebo stimulation

The sham group of MDD will receive sham rTMS stimulation.

Group Type: SHAM_COMPARATOR

sham stimulation

Intervention Type: 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.

accelerated intermittent theta burst stimulation

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.

Group Type: ACTIVE_COMPARATOR

accelerated intermittent theta burst stimulation

Intervention Type: 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.

high frequency stimulation

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.

Group Type: ACTIVE_COMPARATOR

high frequency stimulation

Intervention Type: 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.

Interventions

sham stimulation

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.

Intervention Type: DEVICE

accelerated intermittent theta burst stimulation

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.

Intervention Type: DEVICE

high frequency stimulation

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.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• 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;

Exclusion Criteria

• 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.

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

First Affiliated Hospital of Zhejiang University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

the First Affiliated Hospital,Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Site Status: RECRUITING

Countries

China

Facility Contacts

Manli Huang, Dr

Role: primary

huangmanli@zju.edu.cn

+86 13957162975

Other Identifiers

IITA20230315

Identifier Type: -

Identifier Source: org_study_id