Bipolar DisorderNCT05393648
Bipolar Efficacy Biomarkers for rTMS
A study testing Accelerated Theta Burst Stimulation in people with Bipolar Disorder and Bipolar Depression, run by University of California, San Diego at 1 site in United States.
Trial summary
The research study is being conducted to test whether using high dose spaced theta-burst rTMS (a form of repetitive transcranial magnetic stimulation) produces a significant reduction in depressive symptoms compared with sham. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Bipolar Disorder, Bipolar Depression
- What is being tested?
- Accelerated Theta Burst Stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Jul 2022to 31 Dec 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Bipolar depression (BP I and BP II) by DSM 5 criteria (Diagnostic and Statistical Manual of Mental Disorders, 2013)
- Age 18-70
- Right or left handed
- All genders
- Treatment resistant depression, as in they must have treatment resistant depression with 2 or more prior antidepressant trials that have failed to produce a response (> 50% reduction in symptoms) using ATHF criteria (Sackeim et al., 2019)
- Able to provide informed consent to participate in the study
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- Must be on a stable medication regimen, requiring at least one mood stabilizer
- Depression severity as represented by scoring at least 20 on MADRS
- Meet the safety criteria as defined in the transcranial magnetic stimulation adult safety screen (TASS).
Who cannot join
- No current substance abuse disorder for the past 6 months (previous substance abuse not exclusionary)
- Any psychotic disorder or current active psychotic symptoms (personality disorders not exclusionary unless in the opinion of the referring psychiatrist it would jeopardize participation)
- No dementia or other major neurological disorders
- Not having depression as primary disorder
- No major medical illness, for example metastatic cancer, end stage renal disease
- Not able to verify contact information. Participants must be able to follow through with the study \& must have verified contact information and at least one verified contact
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- Pregnancy. While there are no known risks to a fetus this is a new use of TMS, which has not been tested, thus pregnancy is exclusionary
- Score on YMRS greater than 12 (patients with mixed features have been shown not to respond well to TMS treatment (Tavares et al., 2021).
- Rapid cycling Bipolar illness (patients with > 4 mood episodes within the past year will be excluded, as they have a higher risk of switch to mania (Tondo et al., 2010)
- Any implants, conditions, or contraindications that would be deemed unsafe for TMS or MRI
Trial locations and contacts
1 site in 1 country.
United States1 site
UCSD Interventional Psychiatry
San Diego, California, 92127
About this study
Official title: Bipolar Efficacy Biomarkers for Accelerated Intermittent Theta Burst rTMS Trial
The research study is being conducted to test whether using high dose spaced theta-burst rTMS (a form of repetitive transcranial magnetic stimulation) produces a significant reduction in depressive symptoms compared with sham. This project will recruit patients aged 18-70 with symptoms of bipolar depression (BPD) who have failed (or not shown signs of improvement) after at least two prior treatments. The null hypothesis is that there will be no difference in reductions in depressive symptoms by the end of a five-day treatment period. The alternative hypothesis is that, compared with sham, active TMS will result in a greater reduction in depressive symptoms by the end of the treatment period.
To facilitate the development of rTMS protocols there is a need for biomarkers that are sensitive to BPD symptom severity and clinical improvement. Previously in our lab, investigators developed biomarkers suitable for depression trials, and these biomarkers are very likely to show sensitivity to BPD, since they are associated with brain regions and functions associated with BPD. As a secondary aim, the investigators will try to identify biomarkers in cortical region associated with BPD, and formulate a statistical model that may be able to predict BPD remission after the treatment. this study will lead to development of new brain stimulation treatment protocols and biomarkers, will aid in treatment selection, and eventually lead to better clinical outcome for patients suffering from BPD.
- Conditions
- Bipolar Disorder, Bipolar Depression
- Being tested
- Accelerated Theta Burst Stimulation, Sham accelerated Theta Burst Stimulation
- Keywords
- theta burst stimulation, accelerated TBS
- Medical subject headings
- Bipolar Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Accelerated Theta Burst StimulationDevice
Cool B65- A/P - active side magnetic coil stimulation applied to the left dorsal lateral prefrontal cortex.
Sham accelerated Theta Burst StimulationDevice
Cool-B65 A/P - sham side magnetic coil stimulation applied to the left dorsal lateral prefrontal cortex.
| Study group | Role | What they receive |
|---|---|---|
| Active iTBS | Experimental | Patients will receive unilateral accelerated theta-burst stimulation to the left dorsal lateral prefrontal cortex for 5 consecutive days, with a total of 10 hours a day. Treatment will be 10min with 50min of breaks in between the 10 sessions. Receives: Device: Accelerated Theta Burst Stimulation |
| Sham iTBS | Placebo comparator | Patients will receive sham unilateral accelerated theta-burst stimulation to the left dorsal lateral prefrontal cortex for 5 consecutive days, with a total of 10 hours a day. Treatment will be 10min with 50min of breaks in between the 10 sessions. Receives: Device: Sham accelerated Theta Burst Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Montgomery-Asberg Depression Rating Scale (MADRS) Scores
Assessment of the clinical efficacy, safety, and tolerability of aiTBS for depressive symptoms in BPD by analysis of scores on the Montgomery-Asberg Depression Rating Scale (MADRS) obtained at baseline, post-treatment, and throughout the course of treatment, and comparing them between active vs. sham TMS treatment groups. Scores on the MADRS range from 0 to 60, with higher scores indicating more severe depression.
Measured: 6 months
Change in Hamilton Rating Scale for Depression (HRSD-17) Scores
Assessment of the clinical efficacy, safety, and tolerability of aiTBS for depressive symptoms in BPD by analysis of scores on the Hamilton Rating Scale for Depression (HRSD-17) obtained at baseline, post-treatment, and throughout the course of treatment, and comparing them between active vs. sham TMS treatment groups. Scores on the MADRS range from 0 to 53, with higher scores indicating more severe depression.
Measured: 6 months
Assessment of Biomarkers
Analysis of transcranial magnetic stimulation concurrent with electroencephalogram (TMS-EEG) to extract effective connectivity metrics between the subgenual cingulate (SGC) and the left dorsolateral prefrontal cortex (DLPFC) as BPD biomarkers, as measured by scores on the HAMD and MADRS, for aiTBS compared to sham treatment.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 May 2022
- Study start5 Jul 2022
- Primary completion31 Dec 2024 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bipolar DisorderStudies of the same condition, open and under way.
- More trials run by University of California, San DiegoThe 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
- Model description
- Patients enrolled in the study will be randomized to sham vs. active accelerated iTBS in a 1:1 ratio. Treatments will be over 1 week.
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of California, San Diego
- Sponsor type
- University, hospital or other
- Collaborators
- University of Pennsylvania, Milken Institute
- Responsible party
- Principal investigator, Itay Hadas, University of California, San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05393648
- Sponsor's protocol ID
- 800601
- Status last verified
- Feb 2024
- First submitted
- 5 May 2022
- Last updated
- 4 Mar 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bipolar Efficacy Biomarkers for Accelerated Intermittent Theta Burst rTMS Trial
- ClinicalTrials.gov ID
- NCT05393648
- Acronym / sponsor ID
- 800601
- Conditions
- Bipolar Disorder, Bipolar Depression
- Keywords
- theta burst stimulation, accelerated TBS
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- University of California, San DiegoUniversity, hospital or other
- Collaborators
- University of Pennsylvania, Milken Institute
- Study start
- 5 Jul 2022 (actual)
- Primary completion
- 31 Dec 2024 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 26 May 2022 (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.
The research study is being conducted to test whether using high dose spaced theta-burst rTMS (a form of repetitive transcranial magnetic stimulation) produces a significant reduction in depressive symptoms compared with sham. This project will recruit patients aged 18-70 with symptoms of bipolar depression (BPD) who have failed (or not shown signs of improvement) after at least two prior treatments. The null hypothesis is that there will be no difference in reductions in depressive symptoms by the end of a five-day treatment period. The alternative hypothesis is that, compared with sham, active TMS will result in a greater reduction in depressive symptoms by the end of the treatment period.
To facilitate the development of rTMS protocols there is a need for biomarkers that are sensitive to BPD symptom severity and clinical improvement. Previously in our lab, investigators developed biomarkers suitable for depression trials, and these biomarkers are very likely to show sensitivity to BPD, since they are associated with brain regions and functions associated with BPD. As a secondary aim, the investigators will try to identify biomarkers in cortical region associated with BPD, and formulate a statistical model that may be able to predict BPD remission after the treatment. this study will lead to development of new brain stimulation treatment protocols and biomarkers, will aid in treatment selection, and eventually lead to better clinical outcome for patients suffering from BPD.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- Patients enrolled in the study will be randomized to sham vs. active accelerated iTBS in a 1:1 ratio. Treatments will be over 1 week.
| Arm | Type | Receives |
|---|---|---|
| Active iTBS | Experimental | Device: Accelerated Theta Burst StimulationPatients will receive unilateral accelerated theta-burst stimulation to the left dorsal lateral prefrontal cortex for 5 consecutive days, with a total of 10 hours a day. Treatment will be 10min with 50min of breaks in between the 10 sessions. |
| Sham iTBS | Placebo comparator | Device: Sham accelerated Theta Burst StimulationPatients will receive sham unilateral accelerated theta-burst stimulation to the left dorsal lateral prefrontal cortex for 5 consecutive days, with a total of 10 hours a day. Treatment will be 10min with 50min of breaks in between the 10 sessions. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Bipolar depression (BP I and BP II) by DSM 5 criteria (Diagnostic and Statistical Manual of Mental Disorders, 2013)
- Age 18-70
- Right or left handed
- All genders
- Treatment resistant depression, as in they must have treatment resistant depression with 2 or more prior antidepressant trials that have failed to produce a response (> 50% reduction in symptoms) using ATHF criteria (Sackeim et al., 2019)
Key exclusion criteria (10 listed)
- No current substance abuse disorder for the past 6 months (previous substance abuse not exclusionary)
- Any psychotic disorder or current active psychotic symptoms (personality disorders not exclusionary unless in the opinion of the referring psychiatrist it would jeopardize participation)
- No dementia or other major neurological disorders
- Not having depression as primary disorder
- No major medical illness, for example metastatic cancer, end stage renal disease
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 |
|---|---|---|
| Accelerated Theta Burst StimulationCool B65- A/P - active side magnetic coil stimulation applied to the left dorsal lateral prefrontal cortex. | Device | Active iTBS |
| Sham accelerated Theta Burst StimulationCool-B65 A/P - sham side magnetic coil stimulation applied to the left dorsal lateral prefrontal cortex. | Device | Sham iTBS |
Primary outcome
Change in Montgomery-Asberg Depression Rating Scale (MADRS) Scores
Time frame: 6 months
Assessment of the clinical efficacy, safety, and tolerability of aiTBS for depressive symptoms in BPD by analysis of scores on the Montgomery-Asberg Depression Rating Scale (MADRS) obtained at baseline, post-treatment, and throughout the course of treatment, and comparing them between active vs. sham TMS treatment groups. Scores on the MADRS range from 0 to 60, with higher scores indicating more severe depression.
Change in Hamilton Rating Scale for Depression (HRSD-17) Scores
Time frame: 6 months
Assessment of the clinical efficacy, safety, and tolerability of aiTBS for depressive symptoms in BPD by analysis of scores on the Hamilton Rating Scale for Depression (HRSD-17) obtained at baseline, post-treatment, and throughout the course of treatment, and comparing them between active vs. sham TMS treatment groups. Scores on the MADRS range from 0 to 53, with higher scores indicating more severe depression.
Assessment of Biomarkers
Time frame: 6 months
Analysis of transcranial magnetic stimulation concurrent with electroencephalogram (TMS-EEG) to extract effective connectivity metrics between the subgenual cingulate (SGC) and the left dorsolateral prefrontal cortex (DLPFC) as BPD biomarkers, as measured by scores on the HAMD and MADRS, for aiTBS compared to sham treatment.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2024.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
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 Theta Burst Stimulation in people with Bipolar Disorder and Bipolar Depression, run by University of California, San Diego at 1 site in United States.
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 9 inclusion and 10 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: status not confirmed, as of the sponsor's last update on 4 Mar 2024. 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 United States. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Montgomery-Asberg Depression Rating Scale (MADRS) Scores (time frame: 6 months). 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 4 Mar 2024.