Anxiety DisordersPhase 2ConTRANCT06376877
Connectomic Targeted TMS Target for Refractory Anxiety
A Phase 2 study testing Transcranial magnetic stimulation in people with Anxiety Disorders and Mental Disorder, run by Brigham and Women's Hospital at 1 site in United States.
Trial summary
We will perform a randomized sham-controlled trial of aiTBS to an anxiosomatic circuit in patients with anxiety-related disorders (i.e., panic disorder, generalized anxiety disorder, social anxiety disorder, obsessive-compulsive disorder, and post-traumatic stress disorder). Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Anxiety Disorders, Mental Disorder, Psychiatric Disorder
- What is being tested?
- Transcranial magnetic stimulation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Aug 2024to 1 Feb 2029
- Phase
- Phase 2
- 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 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- English proficiency sufficient for informed consent, questionnaires/tasks, and treatment
- Diagnosis of one of the following anxiety-related disorders per Quick-SCID:
- Generalized Anxiety Disorder
- Social Anxiety Disorder
- Panic Disorder
- Posttraumatic Stress Disorder
Show all 12Show fewer
- Obsessive Compulsive Disorder
- Moderate level of anxiety (BAI >16)
- One failed psychological or pharmacological treatment
- Stable psychiatric medication regimen for 4 weeks prior to treatment and throughout treatment
- Primary clinician (e.g. psychiatrist, psychologist, therapist, APRN, PA, etc.) responsible for psychiatric care before, during, and after the trial
- Agreement to abstaining from becoming pregnant from screening to two weeks after treatment (the MRI visit)
Who cannot join
- • Active pregnancy as determined by a urine pregnancy test
- Recent (within 4 weeks) or concurrent use of rapid acting antidepressant agent (ketamine/esketamine/ECT)
- History of:
- Exposure to TMS within the last 3 months
- Neurosurgical intervention for psychiatric disorders
- Autism spectrum disorder, intellectual disability, or cognitive impairment that impairs capacity to consent
Show all 20Show fewer
- Significant neurological illness deemed to increase risk from treatment
- Moderate to severe neurodegenerative disease
- Untreated or insufficiently treated endocrine disorder
- Treatment with investigational drug or intervention during the study period
- Bipolar I disorder or schizophrenia
- Anyone presenting with:
- Mania or hypomania
- Psychosis
- Active suicidal ideation with intent and a plan (defined by Columbia Suicide Severity Rating Scale)
- Contraindications to either TMS or MRI (e.g., metallic implants, severe insomnia > 4 hours per night with hypnotic, etc.).
- Current moderate or severe substance use disorder (excluding cannabis or nicotine) or demonstrating signs of acute substance withdrawal
- Positive urine drug screen for illicit substances for cocaine, amphetamines, phencyclidine, and opioids, except for prescribed medications or known medications with history of resulting in a false positive
- Existing tinnitus (ringing in the ears)
- Any other condition deemed by the PI to interfere with the study or increase risk to the participant
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
Emma Jones
Boston, Massachusetts, 02115
Emma Jones, bwhtmsanxiety@mgb.org
About this study
Official title: A Novel TMS Target for Anxiety: a Confirmatory Randomized Clinical Trial
We will perform a randomized sham-controlled trial of aiTBS to an anxiosomatic circuit in patients with anxiety-related disorders (i.e., panic disorder, generalized anxiety disorder, social anxiety disorder, obsessive-compulsive disorder, and post-traumatic stress disorder). 80 participants with an anxiety-related disorder (defined below) will receive 50 active or sham TMS treatments over 5 days (following the SAINT protocol, which is FDA-cleared for MDD. The primary outcome will be the BAI, with a modified recall window to reflect the short treatment interval. Participants randomized to sham will be offered an open-label crossover extension.
Read the detailed description
We recently derived a novel TMS target for anxiety via lesion and brain stimulation mapping methods. We prospectively tested this target in a sample of participants with major depressive disorder (MDD) with comorbid anxiety symptoms and found that it was more effective for anxiety (median change 60.0% vs 39.8%, p=0.01) than the conventional TMS target for MDD with comorbid anxiety. While these results are promising, it remains unclear how our target works for anxiety-related disorders as opposed to MDD comorbid anxiety symptoms. Furthermore, we used conventional 10 Hz TMS, but accelerated intermittent theta burst stimulation (aiTBS) has now been shown to improve outcomes and is now an FDA approved treatment protocol. Finally, we tested the translational hypothesis that stimulating different circuits can modify different behaviors; clinical efficacy was a secondary outcome.
This double-blinded, randomized, sham-controlled aiTBS trial will test the efficacy of our novel anxiety target. 80 participants with anxiety-related disorders (i.e., panic disorder, generalized anxiety disorder, social anxiety disorder, obsessive-compulsive disorder, and post-traumatic stress disorder) will receive 50 active or sham TMS treatments over 5 days. Changes in anxiety symptoms/processes will be assessed via validated measures (primary outcome measure: Beck Anxiety Inventory) during treatment and follow-up visits up to one-year post-treatment. Participants randomized to sham who do not respond will be offered an open-label crossover extension.
- Conditions
- Anxiety Disorders, Mental Disorder, Psychiatric Disorder
- Being tested
- Transcranial magnetic stimulation, Sham transcranial magnetic stimulation
- Keywords
- Transcranial Magnetic Stimulation, accelerated intermittent theta burst stimulation, theta burst stimulation, brain stimulation, neuromodulation, anxiety, transcranial, TMS, neuronavigation, neuroimaging
- Medical subject headings
- Anxiety Disorders, Mental Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcranial magnetic stimulationProcedure or surgery
Transcranial magnetic stimulation (TMS) is a focal, non-invasive form of brain stimulation that has FDA clearance for depression. In this study, a form of TMS called accelerated intermittent theta burst stimulation will be administered under the supervision of a physician with TMS expertise.
Sham transcranial magnetic stimulationProcedure or surgery
The sham TMS coil mimics the scalp sensation of real TMS by delivering a small amount of electrical current with a pair of surface electrodes.
| Study group | Role | What they receive |
|---|---|---|
| Real aiTBS | Active comparator | Participants in this group will receive aiTBS with neuronavigation to the anxiosomatic treatment target. Receives: Procedure: Transcranial magnetic stimulation |
| Sham aiTBS | Sham comparator | Participants in this group will receive sham aiTBS with neuronavigation to the anxiosomatic treatment target. Receives: Procedure: Sham transcranial magnetic stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Beck Anxiety Inventory (BAI)
21 item self-report scale that assesses anxiety symptoms, with a particular emphasis on physiological anxiety symptoms
Measured: One week and one month after treatment
Secondary outcomes (11)
Inventory of Depression and Anxiety Symptoms-II
99 item self-report scale of mood (e.g. dysphoria, suicidality, mania) and anxiety (e.g. social anxiety, panic, checking/ordering, traumatic avoidance/intrusion)
Measured: One week and one month after treatment
Hierarchical Taxonomy of Psychopathology (HiTOP)-Self Report, Distress, Fear, and Mania subfactors
HiTOP is a psychiatric nosology that organizes dimensional constructs across multiple levels of abstraction (from broad spectra to specific symptoms). The HiTOP-self report Distress, Fear, and Mania subfactors contain 117 items that capture a broad range of specific mood and anxiety-relevant symptoms
Measured: One week and one month after treatment
State-Trait Anxiety Inventory
40 item self-report scale of present anxiety (i.e., state anxiety) and the general tendency toward anxiety
Measured: One week and one month after treatment
Penn State Worry Questionnaire (PSWQ)
16 item self-report scale of trait worry and anxious apprehension, a transdiagnostic construct characterized by a persistent pattern of negative future thinking
Measured: One week and one month after treatment
Mood/Anxiety Symptoms Questionnaire: Anxious Arousal (MASQ:AA)
90 item self-report with a 17 item scale that measures anxious arousal, a transdiagnostic construct characterized by a persistent pattern of hyperarousal/hypervigilance
Measured: One week and one month after treatment
Anxiety Sensitivity Index (ASI)
16 item self-report scale of concern about anxious cognitions/physiological sensations
Measured: One week and one month after treatment
Intolerance of Uncertainty Scale (IUS)
27 item self-report scale that measures cognitive, emotional, and behavioral reactions to the potential occurrence and unpredictability of negative future events
Measured: One week and one month after treatment
Beck Depression Inventory (BDI)
21 item self-report scale that assesses depression symptoms
Measured: One week and one month after treatment
TCI-R140 (Temperament and character inventory, revised 140-question format)
Psychobiologically-based personality inventory which measures seven personality dimensions (harm avoidance, novelty seeking, reward dependence, persistence, self-directedness, cooperativeness, and persistence). For each dimension, this yields a scaled T-score (mean score of 50 with standard deviation of 10). This is an overall estimate of personality traits, and there are no "better" or "worse" traits.
Measured: One week and one month after treatment
Emotional Conflict Resolution Task
Computer task measuring accuracy and reaction time
Measured: One week after treatment
Laboratory Fear Extinction Paradigm
We will use a validated fear extinction task (24) to assess the effects of anxiosomatic circuit TMS on fear discrimination and fear extinction. This task will consist of two learning phases: fear conditioning and fear extinction. We will measure fear via the skin conductance response.
Measured: One week after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2024
- Study start1 Aug 2024 (estimated)
- Primary completion1 Aug 2028 (estimated)
- Study completion1 Feb 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Anxiety DisordersStudies of the same condition, open and under way.
- More trials run by Brigham and Women's 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Nonresponders may have the option for open label active treatment.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Shan Siddiqi, MD, Brigham and Women's Hospital
- Investigators
- Shan Siddiqi, MD, Principal investigator, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06376877
- Sponsor's protocol ID
- 2024P000900
- Acronym
- ConTRA
- Status last verified
- Apr 2024
- First submitted
- 17 Apr 2024
- Last updated
- 19 Apr 2024
- 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 19 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Novel TMS Target for Anxiety: a Confirmatory Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT06376877
- Acronym / sponsor ID
- ConTRA / 2024P000900
- Conditions
- Anxiety Disorders, Mental Disorder, Psychiatric Disorder
- Keywords
- Transcranial Magnetic Stimulation, accelerated intermittent theta burst stimulation, theta burst stimulation, brain stimulation, neuromodulation, anxiety, transcranial, TMS
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Study start
- 1 Aug 2024 (estimated)
- Primary completion
- 1 Aug 2028 (estimated)
- Study completion
- 1 Feb 2029 (estimated)
- First posted
- 19 Apr 2024 (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.
We will perform a randomized sham-controlled trial of aiTBS to an anxiosomatic circuit in patients with anxiety-related disorders (i.e., panic disorder, generalized anxiety disorder, social anxiety disorder, obsessive-compulsive disorder, and post-traumatic stress disorder). 80 participants with an anxiety-related disorder (defined below) will receive 50 active or sham TMS treatments over 5 days (following the SAINT protocol, which is FDA-cleared for MDD. The primary outcome will be the BAI, with a modified recall window to reflect the short treatment interval. Participants randomized to sham will be offered an open-label crossover extension.
Detailed description
We recently derived a novel TMS target for anxiety via lesion and brain stimulation mapping methods. We prospectively tested this target in a sample of participants with major depressive disorder (MDD) with comorbid anxiety symptoms and found that it was more effective for anxiety (median change 60.0% vs 39.8%, p=0.01) than the conventional TMS target for MDD with comorbid anxiety. While these results are promising, it remains unclear how our target works for anxiety-related disorders as opposed to MDD comorbid anxiety symptoms. Furthermore, we used conventional 10 Hz TMS, but accelerated intermittent theta burst stimulation (aiTBS) has now been shown to improve outcomes and is now an FDA approved treatment protocol. Finally, we tested the translational hypothesis that stimulating different circuits can modify different behaviors; clinical efficacy was a secondary outcome.
This double-blinded, randomized, sham-controlled aiTBS trial will test the efficacy of our novel anxiety target. 80 participants with anxiety-related disorders (i.e., panic disorder, generalized anxiety disorder, social anxiety disorder, obsessive-compulsive disorder, and post-traumatic stress disorder) will receive 50 active or sham TMS treatments over 5 days. Changes in anxiety symptoms/processes will be assessed via validated measures (primary outcome measure: Beck Anxiety Inventory) during treatment and follow-up visits up to one-year post-treatment. Participants randomized to sham who do not respond will be offered an open-label crossover extension.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Nonresponders may have the option for open label active treatment.
| Arm | Type | Receives |
|---|---|---|
| Real aiTBS | Active comparator | Procedure: Transcranial magnetic stimulationParticipants in this group will receive aiTBS with neuronavigation to the anxiosomatic treatment target. |
| Sham aiTBS | Sham comparator | Procedure: Sham transcranial magnetic stimulationParticipants in this group will receive sham aiTBS with neuronavigation to the anxiosomatic treatment target. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- English proficiency sufficient for informed consent, questionnaires/tasks, and treatment
- Diagnosis of one of the following anxiety-related disorders per Quick-SCID:
- Moderate level of anxiety (BAI >16)
- One failed psychological or pharmacological treatment
- Stable psychiatric medication regimen for 4 weeks prior to treatment and throughout treatment
Key exclusion criteria (20 listed)
- • Active pregnancy as determined by a urine pregnancy test
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 stimulationTranscranial magnetic stimulation (TMS) is a focal, non-invasive form of brain stimulation that has FDA clearance for depression. In this study, a form of TMS called accelerated intermittent theta burst stimulation will be administered under the supervision of a physician with TMS expertise. | Procedure or surgery | Real aiTBS |
| Sham transcranial magnetic stimulationThe sham TMS coil mimics the scalp sensation of real TMS by delivering a small amount of electrical current with a pair of surface electrodes. | Procedure or surgery | Sham aiTBS |
Primary outcome
Beck Anxiety Inventory (BAI)
Time frame: One week and one month after treatment
21 item self-report scale that assesses anxiety symptoms, with a particular emphasis on physiological anxiety symptoms
11 secondary outcomes
Inventory of Depression and Anxiety Symptoms-II
Time frame: One week and one month after treatment
Hierarchical Taxonomy of Psychopathology (HiTOP)-Self Report, Distress, Fear, and Mania subfactors
Time frame: One week and one month after treatment
State-Trait Anxiety Inventory
Time frame: One week and one month after treatment
Penn State Worry Questionnaire (PSWQ)
Time frame: One week and one month after treatment
Mood/Anxiety Symptoms Questionnaire: Anxious Arousal (MASQ:AA)
Time frame: One week and one month after treatment
Anxiety Sensitivity Index (ASI)
Time frame: One week and one month after treatment
Intolerance of Uncertainty Scale (IUS)
Time frame: One week and one month after treatment
Beck Depression Inventory (BDI)
Time frame: One week and one month after treatment
TCI-R140 (Temperament and character inventory, revised 140-question format)
Time frame: One week and one month after treatment
Emotional Conflict Resolution Task
Time frame: One week after treatment
Laboratory Fear Extinction Paradigm
Time frame: One week after treatment
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 19 Apr 2024.
Related trials for Anxiety Disorders
Active, not recruiting
Supporting Health in Veterans With Heart Failure
Heart Failure
Active, not recruiting
Targeting Social Function in Anxiety and Eating Disorders
Eating Disorders, Anorexia Nervosa
Recruiting
Modulating Escape Using Focused Ultrasound
Anxiety Disorders
RecruitingPhase 1
Open-Label Psilocybin Study in Transdiagnostic Population
Transdiagnostic, Depression - Major Depressive Disorder
RecruitingObservational study
Sensory Profile of People With High Intellectual Potential (HIP)
High Intellectual Potential
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.
Shan Siddiqi, MD principal investigator
Brigham and Women's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Transcranial magnetic stimulation in people with Anxiety Disorders and Mental Disorder, run by Brigham and Women's 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 12 inclusion and 20 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: opening soon, as of the sponsor's last update on 19 Apr 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Contact Emma Jones (617-525-3536, bwhtmsanxiety@mgb.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Beck Anxiety Inventory (BAI) (time frame: One week and one month after treatment). 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 19 Apr 2024; AzTrials last refreshed its copy on 31 Oct 2026.