Bipolar DepressionNCT05228457
Intensive TMS for Bipolar Depression
A study testing Intensive intermittent theta-burst stimulation (iTBS) in people with Bipolar Depression and Treatment Resistant Depression, run by University of Pennsylvania 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 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 Depression, Treatment Resistant Depression
- What is being tested?
- Intensive intermittent theta-burst stimulation (iTBS)
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 34 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Mar 2022to 19 Feb 2024
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 Diagnostic and Statistical Manual 5 (DSM 5) criteria
- 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
- Able to provide informed consent to participate in the study
- Must be on a stable medication regimen, requiring at least one mood stabilizer
- Depression severity as represented by scoring at least 20 on Montgomery-Asberg Depression Rating Scale (MADRS)
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 Young Mania Rating Scale (YMRS) greater than 12 (patients with mixed features have been shown not to respond well to TMS treatment)
- 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)
- Any implants, conditions, or contraindications that would be deemed unsafe for TMS or MRI
- Currently using benzodiazepines (such as lorazepam) with a dose >1 mg per day or equivalent.
Trial locations and contacts
1 site in 1 country.
United States1 site
Center for Neuromodulation in Depression and Stress, University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: Intensive TMS for Rapid Relief of Bipolar Depression Symptoms
The research study is being conducted to test whether using high dose spaced theta-burst rTMS (a form of 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 who have failed (or not shown signs of improvement) after at least two prior treatments.
Read the detailed description
The research study is being conducted to test whether using high dose spaced theta-burst rTMS (a form of 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 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. Participants will be randomly assigned to active or sham conditions: 50% to active and 50% to sham.
- Conditions
- Bipolar Depression, Treatment Resistant Depression
- Being tested
- Intensive intermittent theta-burst stimulation (iTBS)
- Medical subject headings
- Bipolar Disorder, Depressive Disorder, Treatment-Resistant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intensive intermittent theta-burst stimulation (iTBS)Device
Intensive iTBS is intermittent theta-burst stimulation (iTBS), a patterned form of repetitive transcranial magnetic stimulation (rTMS) over a specific brain region.
| Study group | Role | What they receive |
|---|---|---|
| Active Transcranial Magnetic Stimulation | Active comparator | Active Intensive iTBS involves intermittent theta-burst stimulation (iTBS), a patterned form of repetitive transcranial magnetic stimulation (rTMS) over the left dorsal lateral prefrontal cortex (L-DLPFC). Receives: Device: Intensive intermittent theta-burst stimulation (iTBS) |
| Sham Transcranial Magnetic Stimulation | Sham comparator | Sham Intensive iTBS involves using the coil's electric stimulation functionality that allows for the delivery of a brief electric pulse to the scalp simultaneous to the TMS pulse, which mimics the scalp sensation from active stimulation. Receives: Device: Intensive intermittent theta-burst stimulation (iTBS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Efficacy of High Dose Spaced Theta Burst (HDS-TBS)
The primary outcome will be based on the set of repeated Montgomery Asberg Depression scores (10 items rated on a 0-6 scale, 0-60 possible score range, with higher scores indicating greater depressive symptomology), obtained at baseline, on each of the five treatment days and post TMS.
Measured: Through study completion, approximately 1 week
Secondary outcomes (1)
Relationship Between Change in Brain Resting State Functional Connectivity and Treatment Effects
The secondary outcome will be the change in the correlation between the dorsolateral prefrontal cortex (DLPFC) and the subgenual anterior cingulate cortex (sgACC) with the Montgomery-Åsberg Depression Rating Scale (MADRS), as assessed through MRI scans conducted at baseline and post-stimulation. Additionally, the change in the correlation within the entire Default Mode Network (DMN) intraconnectivity and MADRS will be measured for both groups (Active vs. Sham). The correlation is measured on a scale from -1 to +1, where -1 indicates the highest negative anticorrelation, +1 represents the highest positive correlation, and 0 signifies no correlation. MADRS is used to assess the clinical effect.
Measured: Upon study completion, approximately 1 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Feb 2022
- Study start1 Mar 2022
- Primary completion19 Feb 2024
- Study completion19 Feb 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Bipolar DepressionStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe 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
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yvette Sheline, University of Pennsylvania
- Investigators
- Yvette Sheline, MD, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05228457
- Sponsor's protocol ID
- 850359
- Status last verified
- Feb 2025
- First submitted
- 13 Jan 2022
- Last updated
- 12 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Publications
Sheline YI, Makhoul W, Batzdorf AS, Nitchie FJ, Lynch KG, Cash R, Balderston NL. Accelerated Intermittent Theta-Burst Stimulation and Treatment-Refractory Bipolar Depression: A Randomized Clinical Trial. JAMA Psychiatry. 2024 Sep 1;81(9):936-941. doi: 10.1001/jamapsychiatry.2024.1787.
PubMed 38985492
Study at a glance
From the registry record, last updated by the sponsor on 12 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intensive TMS for Rapid Relief of Bipolar Depression Symptoms
- ClinicalTrials.gov ID
- NCT05228457
- Acronym / sponsor ID
- 850359
- Conditions
- Bipolar Depression, Treatment Resistant Depression
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- 1 Mar 2022 (actual)
- Primary completion
- 19 Feb 2024 (actual)
- Study completion
- 19 Feb 2024 (actual)
- First posted
- 8 Feb 2022 (actual)
- Results
- Posted 12 Mar 2025
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 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 who have failed (or not shown signs of improvement) after at least two prior treatments.
Detailed description
The research study is being conducted to test whether using high dose spaced theta-burst rTMS (a form of 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 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. Participants will be randomly assigned to active or sham conditions: 50% to active and 50% to sham.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active Transcranial Magnetic Stimulation | Active comparator | Device: Intensive intermittent theta-burst stimulation (iTBS)Active Intensive iTBS involves intermittent theta-burst stimulation (iTBS), a patterned form of repetitive transcranial magnetic stimulation (rTMS) over the left dorsal lateral prefrontal cortex (L-DLPFC). |
| Sham Transcranial Magnetic Stimulation | Sham comparator | Device: Intensive intermittent theta-burst stimulation (iTBS)Sham Intensive iTBS involves using the coil's electric stimulation functionality that allows for the delivery of a brief electric pulse to the scalp simultaneous to the TMS pulse, which mimics the scalp sensation from active stimulation. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Bipolar depression (BP I and BP II) by Diagnostic and Statistical Manual 5 (DSM 5) criteria
- 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
Key exclusion criteria (11 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 |
|---|---|---|
| Intensive intermittent theta-burst stimulation (iTBS)Intensive iTBS is intermittent theta-burst stimulation (iTBS), a patterned form of repetitive transcranial magnetic stimulation (rTMS) over a specific brain region. | Device | Active Transcranial Magnetic Stimulation, Sham Transcranial Magnetic Stimulation |
Primary outcome
Clinical Efficacy of High Dose Spaced Theta Burst (HDS-TBS)
Time frame: Through study completion, approximately 1 week
The primary outcome will be based on the set of repeated Montgomery Asberg Depression scores (10 items rated on a 0-6 scale, 0-60 possible score range, with higher scores indicating greater depressive symptomology), obtained at baseline, on each of the five treatment days and post TMS.
1 secondary outcome
Relationship Between Change in Brain Resting State Functional Connectivity and Treatment Effects
Time frame: Upon study completion, approximately 1 week
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38985492Sheline YI, Makhoul W, Batzdorf AS, Nitchie FJ, Lynch KG, Cash R, Balderston NL. Accelerated Intermittent Theta-Burst Stimulation and Treatment-Refractory Bipolar Depression: A Randomized Clinical Trial. JAMA Psychiatry. 2024 Sep 1;81(9):936-941. doi: 10.1001/jamapsychiatry.2024.1787.
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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.
Yvette Sheline, MD principal investigator
University of Pennsylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Intensive intermittent theta-burst stimulation (iTBS) in people with Bipolar Depression and Treatment Resistant Depression, run by University of Pennsylvania 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 8 inclusion and 11 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: finished, as of the sponsor's last update on 12 Mar 2025. 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?
Yes. Results are posted in the registry (first posted 12 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Clinical Efficacy of High Dose Spaced Theta Burst (HDS-TBS) (time frame: Through study completion, approximately 1 week). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05228457, which also lists 1 linked publication.
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 12 Mar 2025.