Major Depressive DisorderNCT05913960
Accelerated Intermittent Theta-Burst Stimulation Ameliorate Major Depressive Disorder by Regulating CAMKII Pathway
A study testing accelerated intermittent theta burst stimulation and high frequency stimulation in people with Major Depressive Disorder and Major Depressive Disorder, Recurrent, run by First Affiliated Hospital of Zhejiang University at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Major Depressive Disorder, Major Depressive Disorder, Recurrent
- What is being tested?
- accelerated intermittent theta burst stimulation and high frequency stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 90 participants
- Where
- 1 siteChina
- Study dates
- 9 Feb 2023to 15 Mar 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 45 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- 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;
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
the First Affiliated Hospital,Zhejiang University School of Medicine
Hangzhou, Zhejiang
Manli Huang, Dr, +86 13957162975, huangmanli@zju.edu.cn
About this study
Official title: the Mechanism of Accelerated Intermittent Theta Burst Stimulation for Rapid Treatment of Major Depressive Disorder Based on the Prefrontal Excitation-inhibition Balance Regulated by CAMKII Pathway
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.
- Being tested
- sham stimulation, accelerated intermittent theta burst stimulation, high frequency stimulation
- Keywords
- major depressive disoerder, first episode without medication, recurrent unmedicated
- Medical subject headings
- Depressive Disorder, Major, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sham stimulationDevice
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 stimulationDevice
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 stimulationDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| Placebo stimulation | Sham comparator | The sham group of MDD will receive sham rTMS stimulation. Receives: 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. Receives: 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. Receives: Device: high frequency stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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
Measured: 4 weeks
Secondary outcomes (13)
Change in the score of THINC-it.
THINC-it is a computerized cognitive screening tool that is designed to assess cognitive function in adults. THINC-it stands for "THINking Clearly," and it includes a series of brief tests that evaluate several cognitive domains, including attention, working memory, executive function, and processing speed. The tool is administered on a tablet or computer, and it takes approximately 20 minutes to complete.
Measured: Baseline
Change in the score of THINC-it.
THINC-it is a computerized cognitive screening tool that is designed to assess cognitive function in adults. THINC-it stands for "THINking Clearly," and it includes a series of brief tests that evaluate several cognitive domains, including attention, working memory, executive function, and processing speed. The tool is administered on a tablet or computer, and it takes approximately 20 minutes to complete.
Measured: 5 days
Change in the score of THINC-it.
THINC-it is a computerized cognitive screening tool that is designed to assess cognitive function in adults. THINC-it stands for "THINking Clearly," and it includes a series of brief tests that evaluate several cognitive domains, including attention, working memory, executive function, and processing speed. The tool is administered on a tablet or computer, and it takes approximately 20 minutes to complete.
Measured: 4 weeks
Change in neuroimaging using functional magnetic resonance
Scanning functional magnetic resonance. Functional magnetic resonance imaging (fMRI) is a neuroimaging technique that is used to measure changes in brain activity by detecting changes in blood flow. In the context of major depression, fMRI has been used to study changes in brain function that may be associated with the condition. Research using fMRI in major depression has shown that there are alterations in the activity of certain brain regions in people with the condition. Specifically, fMRI studies have identified changes in the activity of the prefrontal cortex, the amygdala, and the hippocampus in people with major depression. Overall, fMRI has provided valuable insights into the neural mechanisms underlying major depression, and may help to inform the development of new treatments for the condition.
Measured: Baseline
Change in neuroimaging using functional magnetic resonance
Scanning functional magnetic resonance. Functional magnetic resonance imaging (fMRI) is a neuroimaging technique that is used to measure changes in brain activity by detecting changes in blood flow. In the context of major depression, fMRI has been used to study changes in brain function that may be associated with the condition. Research using fMRI in major depression has shown that there are alterations in the activity of certain brain regions in people with the condition. Specifically, fMRI studies have identified changes in the activity of the prefrontal cortex, the amygdala, and the hippocampus in people with major depression. Overall, fMRI has provided valuable insights into the neural mechanisms underlying major depression, and may help to inform the development of new treatments for the condition.
Measured: 5 days
Change of blood factor levels
Factors carried by peripheral blood and exosomes(Calcium/calmodulin dependent kinase II, cyclic-AMP dependent protein kinase A,protein kinase C and so on ).
Measured: baseline
Change of blood factor levels
Factors carried by peripheral blood and exosomes(Calcium/calmodulin dependent kinase II, cyclic-AMP dependent protein kinase A,protein kinase C and so on ).
Measured: 5 days
Change of blood factor levels
Factors carried by peripheral blood and exosomes(Calcium/calmodulin dependent kinase II, cyclic-AMP dependent protein kinase A,protein kinase C and so on ).
Measured: 4 weeks
Change in electroencephalogram
Electroencephalogram is collected from 64 electrodes. EEG can be used to identify patterns of brain activity that are associated with the condition and to inform treatment decisions. EEG can be a useful tool for identifying patterns of brain activity that are associated with MDD and for guiding treatment decisions. Neurofeedback and TMS are two approaches that have shown promise in the treatment of MDD. several parameters are analyzed to identify patterns of brain activity that may be associated with the condition. These parameters include: Alpha power, Beta power, Theta power, Delta power, Coherence, and more.
Measured: baseline
Change in electroencephalogram
Electroencephalogram is collected from 64 electrodes. EEG can be used to identify patterns of brain activity that are associated with the condition and to inform treatment decisions. EEG can be a useful tool for identifying patterns of brain activity that are associated with MDD and for guiding treatment decisions. Neurofeedback and TMS are two approaches that have shown promise in the treatment of MDD. several parameters are analyzed to identify patterns of brain activity that may be associated with the condition. These parameters include: Alpha power, Beta power, Theta power, Delta power, Coherence, and more.
Measured: 5 days
Hamilton anxiety scale
Assessement of anxious status.A total score of more than 29 May indicate severe anxiety; Over 21 points, there may be significant anxiety; More than 14 points, may have moderate anxiety; More than 7 points, may have mild anxiety; If the score is less than 7, there are no symptoms of anxiety
Measured: baseline
Hamilton anxiety scale
Assessement of anxious status.A total score of more than 29 May indicate severe anxiety; Over 21 points, there may be significant anxiety; More than 14 points, may have moderate anxiety; More than 7 points, may have mild anxiety; If the score is less than 7, there are no symptoms of anxiety
Measured: 5 days
Hamilton anxiety scale
Assessement of anxious status.A total score of more than 29 May indicate severe anxiety; Over 21 points, there may be significant anxiety; More than 14 points, may have moderate anxiety; More than 7 points, may have mild anxiety; If the score is less than 7, there are no symptoms of anxiety
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2023
- Study start9 Feb 2023
- Primary completion15 Mar 2024 (estimated)
- Study completion15 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by First Affiliated Hospital of Zhejiang UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- First Affiliated Hospital of Zhejiang University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05913960
- Sponsor's protocol ID
- IITA20230315
- Status last verified
- Mar 2023
- First submitted
- 16 Mar 2023
- Last updated
- 22 Jun 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- the Mechanism of Accelerated Intermittent Theta Burst Stimulation for Rapid Treatment of Major Depressive Disorder Based on the Prefrontal Excitation-inhibition Balance Regulated by CAMKII Pathway
- ClinicalTrials.gov ID
- NCT05913960
- Acronym / sponsor ID
- IITA20230315
- Keywords
- major depressive disoerder, first episode without medication, recurrent unmedicated
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- First Affiliated Hospital of Zhejiang UniversityUniversity, hospital or other
- Study start
- 9 Feb 2023 (actual)
- Primary completion
- 15 Mar 2024 (estimated)
- Study completion
- 15 Mar 2027 (estimated)
- First posted
- 22 Jun 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Placebo stimulation | Sham comparator | Device: sham stimulationThe sham group of MDD will receive sham rTMS stimulation. |
| accelerated intermittent theta burst stimulation | Active comparator | Device: accelerated intermittent theta burst stimulationStimulation 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. |
| high frequency stimulation | Active comparator | Device: high frequency stimulationStimulation 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. |
Who may qualify
- Ages
- 12 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- 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;
Key exclusion criteria (7 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| sham stimulationThe parameters in the sham arm will be as above with the internal randomization of the device internally switching to sham in a blinded fashion. | Device | Placebo stimulation |
| accelerated intermittent theta burst stimulationParticipants 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. | Device | accelerated intermittent theta burst stimulation |
| high frequency stimulationParticipants 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. | Device | high frequency stimulation |
Primary outcome
Hamilton depression scale-24
Time frame: baseline
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
Hamilton depression scale-24
Time frame: 5days
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
Hamilton depression scale-24
Time frame: 4 weeks
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
13 secondary outcomes
Change in the score of THINC-it.
Time frame: Baseline
Change in the score of THINC-it.
Time frame: 5 days
Change in the score of THINC-it.
Time frame: 4 weeks
Change in neuroimaging using functional magnetic resonance
Time frame: Baseline
Change in neuroimaging using functional magnetic resonance
Time frame: 5 days
Change of blood factor levels
Time frame: baseline
Change of blood factor levels
Time frame: 5 days
Change of blood factor levels
Time frame: 4 weeks
Change in electroencephalogram
Time frame: baseline
Change in electroencephalogram
Time frame: 5 days
Hamilton anxiety scale
Time frame: baseline
Hamilton anxiety scale
Time frame: 5 days
Hamilton anxiety scale
Time frame: 4 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
the First Affiliated Hospital,Zhejiang University School of Medicine
Hangzhou, China
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing accelerated intermittent theta burst stimulation and high frequency stimulation in people with Major Depressive Disorder and Major Depressive Disorder, Recurrent, run by First Affiliated Hospital of Zhejiang University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 22 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hamilton depression scale-24 (time frame: baseline). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2023.