Bipolar DisorderNCT04284267
Neuromodulation for Enhancement of Emotion Regulation in Bipolar Mood Disorders
A study testing Transcranial Magnetic Stimulation in people with Bipolar Disorder, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
The investigators are conducting this research study to better understand how individuals with bipolar disorder regulate their emotions, and if transcranial magnetic stimulation (TMS) can help improve emotion regulation for individuals with bipolar mood disorders. Read more about this study
- Who is it for?
- Ages 22 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Bipolar Disorder
- What is being tested?
- Transcranial Magnetic Stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Mar 2021to 1 Mar 2026
- 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 22 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Male or female age 18-55
- No history of psychiatric disorder, as assessed using the Mini-International Neuropsychiatric Interview (MINI).
- Non-Clinical Levels of Emotion Dysregulation, as assessed using the Difficulties in Emotion Regulation Scale (DERS) Non-clinical levels of emotion dysregulation will be defined as a score < 80 on the DERS.
- Male or female age 18-55
- Diagnosis of Bipolar I Disorder (BD-I), as assessed through MINI.
- Current mood state euthymic.
- Hamilton-Depression Rating Scale (HAM-D-17) and Young Mania Rating Scale (YMRS) will be used to assess current depressive and manic symptoms. Euthymia will be defined as a HAM-D-17 score <10 and YMRS score <12.
- Clinical Levels of Emotion Dysregulation, as assessed using the DERS. Clinical levels of emotion dysregulation will be defined as a score > 80 on the DERS.
Who cannot join
- Current or history of psychiatric disorders
- Endorsement of clinical levels of emotion dysregulation
- Current or history of: organic mental disorder; substance abuse within the past 12 months and/or history of substance abuse for > 1 year; past or current substance dependence (including alcohol); schizophrenia; delusional disorder; and psychotic disorders.
- Current pregnancy.
- Medical illness or non-psychiatric medical treatment that would likely interfere with study participation
- Neurologic disorder, prior neurosurgical procedure, prior electroconvulsive therapy (ECT) or TMS, history of seizures or head trauma.
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- Presence of metallic implants that would interfere with safety during fMRI scanning.
- Current symptoms of mania or depression (YMRS score >12, HAM-D-17 score >10).
- Medication instability (<3 months).
- Current or history of: organic mental disorder; substance abuse within the past 12 months and/or history of substance abuse for > 1 year; past or current substance dependence (including alcohol), verified by urine toxicology screen; schizophrenia; delusional disorder; and psychotic disorders.
- Current pregnancy.
- Medical illness or non-psychiatric medical treatment that would likely interfere with study participation
- Neurologic disorder, prior neurosurgical procedure, prior ECT or TMS, history of seizures or head trauma.
- Presence of metallic implants that would interfere with safety during fMRI scanning.
Trial locations and contacts
1 site in 1 country.
United States1 site
Martinos Center for Biomedical Imaging
Charlestown, Massachusetts, 02129
About this study
The investigators are conducting this research study to better understand how individuals with bipolar disorder regulate their emotions, and if transcranial magnetic stimulation (TMS) can help improve emotion regulation for individuals with bipolar mood disorders.
Read the detailed description
The objective of this study protocol is to test whether intermittent theta-burst transcranial magnetic stimulation (iTBS-TMS) to ventrolateral prefrontal cortex (VLPFC) or inferior parietal lobule (IPL) can improve performance on emotion regulation tasks in patients with bipolar disorder. Results from this study will help inform future treatment development to improve emotion regulation in patients with bipolar disorder. The study will proceed in two phases: During Phase 1, a cohort of 30 healthy control subjects will be recruited in order to establish a normative sample from which to compare patient data. Functional magnetic resonance imaging (fMRI) data will be collected from healthy control participants during performance on two emotion regulation tasks (probing implicit and explicit emotion regulation). Data from these subjects will provide a normative distribution of VLPFC and IPL function from which to compare individual patients. During Phase 2, a cohort of 30 patients diagnosed with bipolar disorder will be recruited. Patient participants will perform the same two emotion regulation tasks during fMRI scanning. Data from individual patients will be analyzed to detect specific VLPFC and IPL subregions showing activation deviations from healthy controls (Phase 1 data). Patient-specific VLPFC and IPL subregions showing patterns of activation greater than two standard deviations from healthy controls will be used as individualized target sites for TMS stimulation. Patients will then receive high-dose iTBS-TMS (1800 pulses) of the VLPFC and IPL, and sham iTBS-TMS to the dorsomedial prefrontal cortex (dmPFC) across three separate study visits. Order of target stimulation will be randomized across participants. TMS sessions will take approximately 10 minutes and will be immediately followed by an fMRI scanning session, during which participants will again complete the implicit and explicit emotion regulation tasks. TMS sessions will take place in the scanning bay to enable quick transition to the fMRI task. Baseline scanning sessions and either active TMS-fMRI or sham TMS-fMRI sessions will occur on separate days, no more than two weeks apart. Effects of iTBS-TMS on emotion regulation will be evaluated by comparing pre-TMS versus post-TMS behavior, neural activation, and functional connectivity patterns during performance on implicit and explicit emotion regulation tasks.
- Conditions
- Bipolar Disorder
- Being tested
- Transcranial Magnetic Stimulation
- Keywords
- Transcranial Magnetic Stimulation, Emotion Regulation
- Medical subject headings
- Bipolar Disorder, Emotional Regulation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcranial Magnetic StimulationDevice
Also called TMS
TMS is a non-invasive tool for modulating patterns of brain activation and circuit connectivity. It uses electromagnetic pulses to induce electric currents over the cortex that serve to depolarize or hyperpolarize neurons, thereby changing patterns of synaptic activity. This study will use intermittent theta burst stimulation (iTBS), an efficient TMS protocol that uses high frequency (50Hz) triplets of TMS given every 200 milliseconds (i.e. at 5 Hz).
| Study group | Role | What they receive |
|---|---|---|
| Healthy Control | No intervention | This group consists of individuals with no psychiatric diagnosis. |
| Bipolar Group | Experimental | This group consists of individuals with a diagnosis of bipolar disorder who have been randomized to receive high-dose TMS (i.e., 1800 pulses) and sham TMS. Receives: Device: Transcranial Magnetic Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Multisource Interference Task with International Affective Pictures Set (MSIT-IAPS)
The MSIT-IAPS task is a well-validated fMRI task designed to assess the effects of emotional distractors on cognitive control. During each trial, a three-digit number is presented. Each set contains two identical distractor numbers and a target number that differed from the distractors. Participants report via a button press the identity of the target number that differs from the two distractor numbers. Noninterference (control) trials: distractor numbers are always zeros, and the identity of the target number always corresponds to its position on the button response pad (100, 020, 003). Interference trials: distractor numbers are always numbers other than 0, and the identity of the target number is always incongruent with its position on the button response pad (e.g. 211, 232, 331, etc.). Each trial of the MSIT is overlaid on a negative, positive, or neutral IAPS image. Reaction time (ms) and accuracy (% correct) is calculated for each trial.
Measured: Change from Baseline to Post-TMS Stimulation (30 min-1 hour)
Emotion Conflict Resolution Task
The ECR task is a well-validated task designed to assess the effects of emotional conflict that arises from the incompatibility between task-relevant and task-irrelevant emotional dimensions of a stimulus. Faces with fearful and happy expressions are presented with the words "happy" or "fear" written across them. Words are either congruent (e.g. "happy" written across an image with a happy expression) or incongruent (e.g. "happy" written across an image with a fearful expression). Subjects are asked to identify the emotional expression of the face while ignoring the word. Trials are analyzed with regard to immediately preceding trials: incongruent trials preceded by congruent trials (CI trials) measure emotion conflict, and incongruent trials preceded by incongruent trials (II trials) measure resolution of emotion conflict. Reaction time (ms) and accuracy (% correct) is calculated for each trial.
Measured: Change from Baseline to Post-TMS Stimulation (30 min-1 hour)
Secondary outcomes (4)
MSIT-IAPS Task-induced blood oxygen level dependent (BOLD) signal
Task-dependent linear time course (ß-value) of BOLD signal during performance of MSIT-IAPS task. Differences in ß-values during relevant task conditions (CI versus II) are compared.
Measured: Change from Baseline to Post-TMS Stimulation (30 min-1 hour)
MSIT-IAPS Task-induced blood oxygen level dependent (BOLD) signal functional connectivity
Task-dependent BOLD signal correlation strengths (z-transformed values) during performance of the task. Differences in z-transformed values during relevant task conditions (CI versus II) are compared.
Measured: Change from Baseline to Post-TMS Stimulation (30 min-1 hour)
ECR Task-induced blood oxygen level dependent (BOLD) signal
Task-dependent linear time course (ß-value) of BOLD signal during performance of the ECR task. Differences in ß-values during relevant task conditions (II vs CI) are compared.
Measured: Change from Baseline to Post-TMS Stimulation (30 min-1 hour)
ECR Task-induced blood oxygen level dependent (BOLD) signal functional connectivity
Task-dependent BOLD signal correlation strengths (z-transformed values) during performance of the ECR task. Differences in ztransformed values during relevant task conditions (II versus CI) are compared.
Measured: Change from Baseline to Post-TMS Stimulation (30 min-1 hour)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2020
- Study start1 Mar 2021
- Primary completion30 Oct 2025
- Study completion1 Mar 2026
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 Massachusetts General HospitalThe 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
- Factorial
- Model description
- There will be a healthy control group and a bipolar disorder group. The bipolar disorder group will then be randomized to one of three conditions.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kristen K. Ellard, Ph.D., Massachusetts General Hospital
- Investigators
- Kristen Ellard, PhD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04284267
- Sponsor's protocol ID
- 2020P000120
- Status last verified
- Oct 2026
- First submitted
- 20 Feb 2020
- Last updated
- 26 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neuromodulation for Enhancement of Emotion Regulation in Bipolar Mood Disorders
- ClinicalTrials.gov ID
- NCT04284267
- Acronym / sponsor ID
- 2020P000120
- Conditions
- Bipolar Disorder
- Keywords
- Transcranial Magnetic Stimulation, Emotion Regulation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- 1 Mar 2021 (actual)
- Primary completion
- 30 Oct 2025 (actual)
- Study completion
- 1 Mar 2026 (actual)
- First posted
- 25 Feb 2020 (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 investigators are conducting this research study to better understand how individuals with bipolar disorder regulate their emotions, and if transcranial magnetic stimulation (TMS) can help improve emotion regulation for individuals with bipolar mood disorders.
Detailed description
The objective of this study protocol is to test whether intermittent theta-burst transcranial magnetic stimulation (iTBS-TMS) to ventrolateral prefrontal cortex (VLPFC) or inferior parietal lobule (IPL) can improve performance on emotion regulation tasks in patients with bipolar disorder. Results from this study will help inform future treatment development to improve emotion regulation in patients with bipolar disorder. The study will proceed in two phases: During Phase 1, a cohort of 30 healthy control subjects will be recruited in order to establish a normative sample from which to compare patient data. Functional magnetic resonance imaging (fMRI) data will be collected from healthy control participants during performance on two emotion regulation tasks (probing implicit and explicit emotion regulation). Data from these subjects will provide a normative distribution of VLPFC and IPL function from which to compare individual patients. During Phase 2, a cohort of 30 patients diagnosed with bipolar disorder will be recruited. Patient participants will perform the same two emotion regulation tasks during fMRI scanning. Data from individual patients will be analyzed to detect specific VLPFC and IPL subregions showing activation deviations from healthy controls (Phase 1 data). Patient-specific VLPFC and IPL subregions showing patterns of activation greater than two standard deviations from healthy controls will be used as individualized target sites for TMS stimulation. Patients will then receive high-dose iTBS-TMS (1800 pulses) of the VLPFC and IPL, and sham iTBS-TMS to the dorsomedial prefrontal cortex (dmPFC) across three separate study visits. Order of target stimulation will be randomized across participants. TMS sessions will take approximately 10 minutes and will be immediately followed by an fMRI scanning session, during which participants will again complete the implicit and explicit emotion regulation tasks. TMS sessions will take place in the scanning bay to enable quick transition to the fMRI task. Baseline scanning sessions and either active TMS-fMRI or sham TMS-fMRI sessions will occur on separate days, no more than two weeks apart. Effects of iTBS-TMS on emotion regulation will be evaluated by comparing pre-TMS versus post-TMS behavior, neural activation, and functional connectivity patterns during performance on implicit and explicit emotion regulation tasks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- There will be a healthy control group and a bipolar disorder group. The bipolar disorder group will then be randomized to one of three conditions.
| Arm | Type | Receives |
|---|---|---|
| Healthy Control | No intervention | –This group consists of individuals with no psychiatric diagnosis. |
| Bipolar Group | Experimental | Device: Transcranial Magnetic StimulationThis group consists of individuals with a diagnosis of bipolar disorder who have been randomized to receive high-dose TMS (i.e., 1800 pulses) and sham TMS. |
Who may qualify
- Ages
- 22 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Male or female age 18-55
- No history of psychiatric disorder, as assessed using the Mini-International Neuropsychiatric Interview (MINI).
- Non-Clinical Levels of Emotion Dysregulation, as assessed using the Difficulties in Emotion Regulation Scale (DERS) Non-clinical levels of emotion dysregulation will be defined as a score < 80 on the DERS.
- Male or female age 18-55
- Diagnosis of Bipolar I Disorder (BD-I), as assessed through MINI.
Key exclusion criteria (14 listed)
- Current or history of psychiatric disorders
- Endorsement of clinical levels of emotion dysregulation
- Current or history of: organic mental disorder; substance abuse within the past 12 months and/or history of substance abuse for > 1 year; past or current substance dependence (including alcohol); schizophrenia; delusional disorder; and psychotic disorders.
- Current pregnancy.
- Medical illness or non-psychiatric medical treatment that would likely interfere with study participation
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 |
|---|---|---|
| Transcranial Magnetic StimulationAlso: TMSTMS is a non-invasive tool for modulating patterns of brain activation and circuit connectivity. It uses electromagnetic pulses to induce electric currents over the cortex that serve to depolarize or hyperpolarize neurons, thereby changing patterns of synaptic activity. This study will use intermittent theta burst stimulation (iTBS), an efficient TMS protocol that uses high frequency (50Hz) triplets of TMS given every 200 milliseconds (i.e. at 5 Hz). | Device | Bipolar Group |
Primary outcome
Multisource Interference Task with International Affective Pictures Set (MSIT-IAPS)
Time frame: Change from Baseline to Post-TMS Stimulation (30 min-1 hour)
The MSIT-IAPS task is a well-validated fMRI task designed to assess the effects of emotional distractors on cognitive control. During each trial, a three-digit number is presented. Each set contains two identical distractor numbers and a target number that differed from the distractors. Participants report via a button press the identity of the target number that differs from the two distractor numbers. Noninterference (control) trials: distractor numbers are always zeros, and the identity of the target number always corresponds to its position on the button response pad (100, 020, 003). Interference trials: distractor numbers are always numbers other than 0, and the identity of the target number is always incongruent with its position on the button response pad (e.g. 211, 232, 331, etc.). Each trial of the MSIT is overlaid on a negative, positive, or neutral IAPS image. Reaction time (ms) and accuracy (% correct) is calculated for each trial.
Emotion Conflict Resolution Task
Time frame: Change from Baseline to Post-TMS Stimulation (30 min-1 hour)
The ECR task is a well-validated task designed to assess the effects of emotional conflict that arises from the incompatibility between task-relevant and task-irrelevant emotional dimensions of a stimulus. Faces with fearful and happy expressions are presented with the words "happy" or "fear" written across them. Words are either congruent (e.g. "happy" written across an image with a happy expression) or incongruent (e.g. "happy" written across an image with a fearful expression). Subjects are asked to identify the emotional expression of the face while ignoring the word. Trials are analyzed with regard to immediately preceding trials: incongruent trials preceded by congruent trials (CI trials) measure emotion conflict, and incongruent trials preceded by incongruent trials (II trials) measure resolution of emotion conflict. Reaction time (ms) and accuracy (% correct) is calculated for each trial.
4 secondary outcomes
MSIT-IAPS Task-induced blood oxygen level dependent (BOLD) signal
Time frame: Change from Baseline to Post-TMS Stimulation (30 min-1 hour)
MSIT-IAPS Task-induced blood oxygen level dependent (BOLD) signal functional connectivity
Time frame: Change from Baseline to Post-TMS Stimulation (30 min-1 hour)
ECR Task-induced blood oxygen level dependent (BOLD) signal
Time frame: Change from Baseline to Post-TMS Stimulation (30 min-1 hour)
ECR Task-induced blood oxygen level dependent (BOLD) signal functional connectivity
Time frame: Change from Baseline to Post-TMS Stimulation (30 min-1 hour)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2026.
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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.
Kristen Ellard, PhD principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transcranial Magnetic Stimulation in people with Bipolar Disorder, run by Massachusetts General Hospital 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 14 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 26 Oct 2026. 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. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Multisource Interference Task with International Affective Pictures Set (MSIT-IAPS) (time frame: Change from Baseline to Post-TMS Stimulation (30 min-1 hour)). The study lists 2 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 26 Oct 2026.