Clinical trial NCT05680727: Individualized Functional Connectivity Targeting in aiTBS for Depression
Official title: The Role of Individualized Functional Connectivity Targeting in Accelerated Intelligent Neuromodulation Therapy (AINT) for Depression
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Depressive Disorder, Major
Depression
Mood Disorders
Mental Disorder
Psychiatric Disorder
Keywords: transcranial magnetic stimulation
accelerated intermittent theta burst stimulation
theta burst stimulation
brain stimulation
neuromodulation
depression
transcranial
TMS
neuronavigation
functional connectivity
neuroimaging
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
First posted: 2023-01-11
Enrollment: 40
Sex: ALL
Minimum age (years): 22
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel-group double-blind randomized controlled trial
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to estimate the importance of neuroimaging in accelerated intermittent theta burst stimulation (aiTBS) for depression. Participants will receive aiTBS treatment, but they will not know if their treatment spot was found with neuroimaging or head measurements.

Detailed description: Techniques for modulating human brain networks are rapidly evolving. One of the most exciting new developments is accelerated intermittent theta burst stimulation (aiTBS), a transcranial magnetic stimulation (TMS) protocol that involves multiple daily treatments rather than gold standard once daily treatment. A specific accelerated iTBS protocol called Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) was cleared by the FDA in September 2022 based on two pilot studies in which patients with treatment-resistant depression rapidly and robustly improved with SAINT. Many of these patients had been depressed for decades and had not improved with conventional TMS or electroconvulsive therapy. Despite these promising results, two issues may limit SAINT scalability: 1) SAINT has only been tested at a single site in a small number of patients, 2) SAINT has never been tested without individualized resting state functional connectivity (rsfc) targeting, which is not widely available or covered by insurance. In this pilot trial, patients with treatment-resistant depression (n=40) will be randomized to one of two active treatment arms: 1) Real aiTBS with real individualized rsfc targeting, or 2) Real aiTBS with sham individualized rsfc targeting (i.e. conventional TMS targeting based on scalp landmarks). All patients will receive active stimulation, which will facilitate enrollment and reduce ethical concerns about placebo treatment in a vulnerable population when there is existing evidence of treatment efficacy. Patients and clinicians will be blind to group assignment, and blind integrity will be assessed. All patients will undergo MRI scans immediately before treatment and at one month follow up, which aligns with our clinical outcome measures.

Eligibility criteria: Inclusion Criteria:

* English proficiency sufficient for informed consent, questionnaires/tasks, and treatment
* Primary diagnosis of major depressive disorder per Diagnostic and Statistical Manual (DSM)-V criteria (MINI International Neuropsychiatric Interview)
* \>20 on BDI
* \>20 on the MADRS 10, 11
* Moderate to severe level of treatment resistance (Maudsley Staging Method)
* Stable antidepressant medication regimen, or remain medication free, for 4 weeks prior to treatment and to remain on this regimen throughout the study (including all follow-up assessments after the 5-day treatment protocol).
* Primary clinician responsible for psychiatric care before, during, and after the trial
* Agreement to lifestyle considerations
* Abstain from becoming pregnant from screening through end of treatment
* Continue usual intake patterns of caffeine- or xanthine-containing products (e.g., coffee, tea, soft drinks, chocolate) throughout treatment
* Abstain from alcohol for at least 24 hours before the start of each MRI and TMS session
* Abstain from tobacco products during treatment day

Exclusion Criteria:

* Active pregnancy as determined by a urine pregnancy test
* Primary psychiatric diagnosis other than major depressive disorder requiring treatment other than comorbid anxiety disorder
* Those who did not respond to electroconvulsive therapy (ECT) after 8 sessions
* Recent (within 4 weeks) or concurrent use of rapid acting antidepressant agent (ketamine/esketamine/ECT)
* History of:
* Prior exposure to TMS
* Neurosurgical intervention for depression
* Autism spectrum disorder
* Intellectual disability
* Severe cognitive impairment
* Significant neurological illness (e.g., dementia, Parkinson's, Huntington's, brain tumor, seizure disorder, subdural hematoma, multiple sclerosis, brain lesion)
* Untreated or insufficiently treated endocrine disorder
* Treatment with investigational drug or intervention during the study period
* Depth-adjusted TMS treatment dose \> 65% maximum stimulator output
* ≥ 30% change in MADRS score between screening and baseline
* Anyone presenting with:
* Mania or hypomania
* Psychosis
* Active suicidal ideation or a suicide attempt (defined by C-SSRS) within the past year
* Neurological lesion
* 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 or demonstrating signs of acute substance withdrawal
* Positive urine drug screen for illicit substances
* Severe borderline personality disorder
* Any other condition deemed by the PI to interfere with the study or increase risk to the participant

Primary outcomes:
measure: Montgomery-Åsberg Depression Rating Scale (MADRS)
timeFrame: one month after treatment
Secondary outcomes:
measure: Montgomery-Åsberg Depression Rating Scale (MADRS)
timeFrame: immediately after treatment ends
measure: Beck Depression Inventory (BDI)
timeFrame: immediately after treatment ends and at all subsequent timepoints (1 week, 1 month, 3 months, 6 months, 9 months, 12 months)
measure: Quick Inventory of Depressive Symptomatology (QIDS)
timeFrame: immediately after treatment ends and at all subsequent timepoints (1 week, 1 month, 3 months, 6 months, 9 months, 12 months)
measure: Change in resting state functional connectivity in the depression network
timeFrame: one month after treatment
measure: Percentage of screened patients from TMS clinical programs who select the accelerated iTBS trial over routine clinical TMS
timeFrame: through study completion, an average of 2 years
measure: Temperament and Character Inventory, Revised 140-item
timeFrame: one month after treatment
measure: Emotional Conflict Resolution Task
timeFrame: one month after treatment
measure: Learning, Multi-Source Interference Task (MSIT)
timeFrame: one month after treatment
measure: Penn Emotion Recognition Task (ER-40)
timeFrame: one month after treatment
measure: Death Suicide IAT (DSIAT)
timeFrame: one month after treatment
measure: Beck Anxiety Inventory (BAI)
timeFrame: immediately after treatment ends and at all subsequent timepoints (1 week, 1 month, 3 months, 6 months, 9 months, 12 months)
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Joseph J Taylor, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: