Clinical trial NCT05445466: Causal Lesion Network Guided Treatment of Bipolar Mania With Transcranial Electrical Stimulation
Official title: Causal Lesion Network Guided Treatment of Bipolar Mania With Transcranial Electrical Stimulation
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Bipolar Disorder
Schizo Affective Disorder
Keywords: Brain Stimulation
Mania
Lead sponsor: Beth Israel Deaconess Medical Center
Sponsor class: OTHER
First posted: 2022-07-06
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Mania is a core symptom of bipolar disorder involving periods of euphoria. Decreased inhibitory control, increased risk-taking behaviors, and aberrant reward processing are some of the more recognized symptoms of bipolar disorder and are included in the diagnostic criteria for mania. Current drug therapies for mania are frequently intolerable, ineffective, and carry significant risk for side effects. Presently there are no neurobiologically informed therapies that treat or prevent mania. However, using a newly validated technique termed lesion network mapping, researchers demonstrated that focal brain lesions having a causal role in the development of mania in people without a psychiatric history can occur in different brain locations, such as the right orbitofrontal cortex (OFC), right dorsolateral prefrontal cortex (DLPFC), and right inferior temporal gyrus (ITG). This lesion network evidence converges with existing cross-sectional and longitudinal observations in bipolar mania that have identified specific disruptions in network communication between the amygdala and ventro-lateral prefrontal cortex. The OFC is associated with inhibitory control, risk-taking behavior, and reward learning which are major components of bipolar mania. Thus, the association between OFC with mania symptoms, inhibitory control, risk-taking behavior, and reward processing suggests that this region could be targeted using non-invasive brain stimulation.

Detailed description: Mania is a core symptom of bipolar disorder involving periods of euphoria, delusions, and overactivity. Mania occurs in multiple medical and psychiatric illnesses and can be refractory to existing treatments. Two recent studies using brain lesion mapping of psychiatrically healthy individuals presenting with mania identified causal locations in the brain, including the orbitofrontal cortex (OFC), dorsolateral prefrontal cortex (DLPFC), and inferior temporal gyrus (ITG), that were associated with new onset mania symptoms. Moreover, these identified brain regions have also been implicated in bipolar mania with specific disruption in network communication between the amygdala and ventro-lateral prefrontal cortex. The OFC is of particular interest because it is a brain structure that is associated with inhibitory control, risk-taking behavior and reward, which are major behavioral components of mania. Thus, the association between OFC with mania symptoms, inhibitory control, risk-taking behavior and reward suggests that this region could be targeted using noninvasive brain stimulation. While several studies have non-invasively targeted the DLPFC for mania, no study to date has non-invasively stimulated the OFC with either transcranial direct current stimulation (tDCS) or alternating current (tACS) in bipolar disorder and examined its effects on mania, inhibitory control, or risk-taking behavior. However, a study in healthy volunteers showed that cathodal stimulation to the OFC enhanced inhibitory control and decreased risk-taking behavior. Recently, researches have showed that targeting the OFC with tACS, personalized to the individual's intrinsic beta-gamma frequency of the reward network, that individuals showed rapid, reversible, frequency-specific modulation of reward-guided choice behavior and learning. Here we aim to answer the question of whether noninvasive brain stimulation when optimally targeted and personalized to an individual's beta-gamma frequency to the OFC can improve emotional cognitive processing and mania symptoms compared to tDCS or sham targeting. The knowledge gained from this study will provide a marker for clinical response and allow personalized treatment for patients with bipolar disorder.

Eligibility criteria: Inclusion Criteria:

1. Aged 18-65 years of age
2. Proficient in English
3. Able to give informed consent
4. Meet diagnostic criteria for bipolar disorder or schizoaffective disorder, bipolar type as verified by the SCID
5. History of mania ( \>1 lifetime episode)
6. Experiencing mild to moderate symptoms of mania
7. No changes to mood stabilizing medications for a period of 2 weeks prior to participation
8. Has not recently participated in tES/TMS treatments

Exclusion Criteria:

1. Substance abuse or dependence (w/in past 6 months)
2. Those who are pregnant/breastfeeding
3. History of head injury with \> 15 minutes of loss of consciousness/mal sequelae
4. DSM-V intellectual disability
5. Having a non-removable ferromagnetic metal within the body (particularly in the head)
6. History of seizures

Primary outcomes:
measure: Young Mania Rating Scale (YMRS)
timeFrame: Change from baseline to 5 Day follow-up
measure: Young Mania Rating Scale (YMRS)
timeFrame: Change from baseline to 1-month follow-up
measure: Young Mania Rating Scale (YMRS)
timeFrame: Change from baseline to 3-month follow-up
measure: Altman Self-Rating Mania Scale (ASRM)
timeFrame: Change from baseline to 5 Day follow-up
measure: Altman Self-Rating Mania Scale (ASRM)
timeFrame: Change from baseline to 1-month follow-up
measure: Altman Self-Rating Mania Scale (ASRM)
timeFrame: Change from baseline to 3-month follow-up
measure: Psychiatric Hospitalization for Mania
timeFrame: Average per year prior to study entry compared to 1 year post study completion
Secondary outcomes:
measure: Balloon Analogue Risk Task (BART)
timeFrame: Change from baseline to 5 Day follow-up
measure: Balloon Analogue Risk Task (BART)
timeFrame: Change from baseline to 1-month follow-up
measure: Balloon Analogue Risk Task (BART)
timeFrame: Change from baseline to 3-month follow-up
measure: The Go/No Go Task
timeFrame: Change from baseline to 5 Day follow-up
measure: The Go/No Go Task
timeFrame: Change from baseline to 1-month follow-up
measure: The Go/No Go Task
timeFrame: Change from baseline to 3-month follow-up
measure: Electroencephalography (EEG) Resting State
timeFrame: Change from baseline to 5 Day follow-up
measure: Electroencephalography (EEG) Resting State
timeFrame: Change from baseline to 1-month follow-up
measure: Electroencephalography (EEG) Resting State
timeFrame: Change from baseline to 3-month follow-up
measure: Reinforcement Learning Task
timeFrame: Change from baseline to 5 Day follow-up
measure: Reinforcement Learning Task
timeFrame: Change from baseline to 1-month follow-up
measure: Reinforcement Learning Task
timeFrame: Change from baseline to 3-month follow-up
measure: Social Functioning Scale (SFS)
timeFrame: Change from baseline to 5 Day follow-up
measure: Social Functioning Scale (SFS)
timeFrame: Change from baseline to 1-month follow-up
measure: Social Functioning Scale (SFS)
timeFrame: Change from baseline to 3-month follow-up
measure: Global Assessment of Functioning (GAF)
timeFrame: Change from baseline to 5 Day follow-up
measure: Global Assessment of Functioning (GAF)
timeFrame: Change from baseline to 1-month follow-up
measure: Global Assessment of Functioning (GAF)
timeFrame: Change from baseline to 3-month follow-up
measure: Positive and Negative Syndrome Scale (PANSS)
timeFrame: Change from baseline to 5 Day follow-up
measure: Positive and Negative Syndrome Scale (PANSS)
timeFrame: Change from baseline to 1-month follow-up
measure: Positive and Negative Syndrome Scale (PANSS)
timeFrame: Change from baseline to 3-month follow-up
measure: Montgomery-Åsberg Depression Rating Scale (MADRS)
timeFrame: Change from baseline to 5 Day follow-up
measure: Montgomery-Åsberg Depression Rating Scale (MADRS)
timeFrame: Change from baseline to 1-month follow-up
measure: Montgomery-Åsberg Depression Rating Scale (MADRS)
timeFrame: Change from baseline to 3-month follow-up
measure: Barratt Impulsiveness Scale-11 (BIS-11)
timeFrame: Change from baseline to 5 Day follow-up
measure: Barratt Impulsiveness Scale-11 (BIS-11)
timeFrame: Change from baseline to 1-month follow-up
measure: Barratt Impulsiveness Scale-11 (BIS-11)
timeFrame: Change from baseline to 3-month follow-up
measure: Brief Assessment of Cognition (BACS)
timeFrame: Change from baseline to 5 Day follow-up
measure: Brief Assessment of Cognition (BACS)
timeFrame: Change from baseline to 1-month follow-up
measure: Brief Assessment of Cognition (BACS)
timeFrame: Change from baseline to 3-month follow-up
Other outcomes:
Locations:
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
Study officials:
References: