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Causal Lesion Network Guided Treatment of Bipolar Mania With Transcranial Electrical Stimulation

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ClinicalTrials.gov Identifier: NCT05445466
Recruitment Status : Not yet recruiting
First Posted : July 6, 2022
Last Update Posted : July 6, 2022
Sponsor:
Information provided by (Responsible Party):
Paulo Lizano, Beth Israel Deaconess Medical Center

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.

Condition or disease Intervention/treatment Phase
Bipolar Disorder Schizo Affective Disorder Device: High-Definition Transcranial Electrical-Current Stimulation Device: High-Definition Transcranial Alternate-Current Stimulation Device: High-Definition Personalized Beta-Gamma Electrical Stimulation Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Causal Lesion Network Guided Treatment of Bipolar Mania With Transcranial Electrical Stimulation
Estimated Study Start Date : July 1, 2022
Estimated Primary Completion Date : July 1, 2024
Estimated Study Completion Date : July 1, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Active HD-tDCS
10 tDCS; Two, twenty-minute sessions of tDCS to the OFC for 5 days (10 total sessions).
Device: High-Definition Transcranial Electrical-Current Stimulation
Non-frequency dependent transcranial electrical stimulation condition for 5 days of twice a day treatment
Other Names:
  • Soterix Medical
  • GTEN 200

Sham Comparator: Active Control (alpha, 10 Hz)
10 passive sham control; Two, twenty-minute sessions of passive sham control to the OFC for a 30 second ramped up and down at the beginning and end of the 20 min period for 5 days (10 total sessions).
Device: High-Definition Transcranial Alternate-Current Stimulation
Active-control stimulation condition will target alpha (10 Hz) for 5 days of twice a day treatment
Other Names:
  • Soterix Medical
  • GTEN 200

Experimental: Personalized Beta-Gamma tACS
10 tACS; Two, twenty-minute sessions of tACS to the OFC for 5 days (10 total sessions).
Device: High-Definition Personalized Beta-Gamma Electrical Stimulation
Personalized beta-gamma electrical stimulation for 5 days of twice a day treatment
Other Names:
  • Soterix Medical
  • GTEN 200




Primary Outcome Measures :
  1. Young Mania Rating Scale (YMRS) [ Time Frame: Change from baseline to 5 Day follow-up ]
    Measuring total Mania scores; 11 items used to access severity of mania (total score 0-60); higher scores represent higher severity of symptoms

  2. Young Mania Rating Scale (YMRS) [ Time Frame: Change from baseline to 1-month follow-up ]
    Measuring total Mania scores; 11 items used to access severity of mania (total score 0-60); higher scores represent higher severity of symptoms

  3. Young Mania Rating Scale (YMRS) [ Time Frame: Change from baseline to 3-month follow-up ]
    Measuring total Mania scores; 11 items used to access severity of mania (total score 0-60); higher scores represent higher severity of symptoms

  4. Altman Self-Rating Mania Scale (ASRM) [ Time Frame: Change from baseline to 5 Day follow-up ]
    The ASRM is a 5-item self rating mania scale, assessing the presence and severity of manic symptoms. 6 or higher indicates a high probability of a manic or hypomanic condition.

  5. Altman Self-Rating Mania Scale (ASRM) [ Time Frame: Change from baseline to 1-month follow-up ]
    The ASRM is a 5-item self rating mania scale, assessing the presence and severity of manic symptoms. 6 or higher indicates a high probability of a manic or hypomanic condition.

  6. Altman Self-Rating Mania Scale (ASRM) [ Time Frame: Change from baseline to 3-month follow-up ]
    The ASRM is a 5-item self rating mania scale, assessing the presence and severity of manic symptoms. 6 or higher indicates a high probability of a manic or hypomanic condition.

  7. Psychiatric Hospitalization for Mania [ Time Frame: Average per year prior to study entry compared to 1 year post study completion ]
    Psychiatric hospitalization for mania


Secondary Outcome Measures :
  1. Balloon Analogue Risk Task (BART) [ Time Frame: Change from baseline to 5 Day follow-up ]
    The BART is a computerized task the measures risk-taking behavior.

  2. Balloon Analogue Risk Task (BART) [ Time Frame: Change from baseline to 1-month follow-up ]
    The BART is a computerized task the measures risk-taking behavior.

  3. Balloon Analogue Risk Task (BART) [ Time Frame: Change from baseline to 3-month follow-up ]
    The BART is a computerized task the measures risk-taking behavior.

  4. The Go/No Go Task [ Time Frame: Change from baseline to 5 Day follow-up ]
    The Go/No Go Task is a computerized task that measures impulsiveness.

  5. The Go/No Go Task [ Time Frame: Change from baseline to 1-month follow-up ]
    The Go/No Go Task is a computerized task that measures impulsiveness.

  6. The Go/No Go Task [ Time Frame: Change from baseline to 3-month follow-up ]
    The Go/No Go Task is a computerized task that measures impulsiveness.

  7. Electroencephalography (EEG) Resting State [ Time Frame: Change from baseline to 5 Day follow-up ]
    EEG measures neural activity recorded from electrodes placed on the scalp. Resting state measures include connectivity as well as oscillatory characteristics within delta, theta, alpha, beta, gamma bands.

  8. Electroencephalography (EEG) Resting State [ Time Frame: Change from baseline to 1-month follow-up ]
    EEG measures neural activity recorded from electrodes placed on the scalp. Resting state measures include connectivity as well as oscillatory characteristics within delta, theta, alpha, beta, gamma bands.

  9. Electroencephalography (EEG) Resting State [ Time Frame: Change from baseline to 3-month follow-up ]
    EEG measures neural activity recorded from electrodes placed on the scalp. Resting state measures include connectivity as well as oscillatory characteristics within delta, theta, alpha, beta, gamma bands.

  10. Reinforcement Learning Task [ Time Frame: Change from baseline to 5 Day follow-up ]
    The reinforcement learning task is a monetary based learning tasks that included reward and punishment trails.

  11. Reinforcement Learning Task [ Time Frame: Change from baseline to 1-month follow-up ]
    The reinforcement learning task is a monetary based learning tasks that included reward and punishment trails.

  12. Reinforcement Learning Task [ Time Frame: Change from baseline to 3-month follow-up ]
    The reinforcement learning task is a monetary based learning tasks that included reward and punishment trails.

  13. Social Functioning Scale (SFS) [ Time Frame: Change from baseline to 5 Day follow-up ]
    The SFS a self-report questionnaire initially designed for people diagnosed with Schizophrenia; consists of 79 items designed to reflect the social skills and performances in different areas of life. Total score of SFS ranges between 55 - 145 points. Higher scores mean better social functioning.

  14. Social Functioning Scale (SFS) [ Time Frame: Change from baseline to 1-month follow-up ]
    The SFS a self-report questionnaire initially designed for people diagnosed with Schizophrenia; consists of 79 items designed to reflect the social skills and performances in different areas of life. Total score of SFS ranges between 55 - 145 points. Higher scores mean better social functioning.

  15. Social Functioning Scale (SFS) [ Time Frame: Change from baseline to 3-month follow-up ]
    The SFS a self-report questionnaire initially designed for people diagnosed with Schizophrenia; consists of 79 items designed to reflect the social skills and performances in different areas of life. Total score of SFS ranges between 55 - 145 points. Higher scores mean better social functioning.

  16. Global Assessment of Functioning (GAF) [ Time Frame: Change from baseline to 5 Day follow-up ]
    The GAF measures how symptoms affect individuals day-to-day life; scored from 0 to 100

  17. Global Assessment of Functioning (GAF) [ Time Frame: Change from baseline to 1-month follow-up ]
    The GAF measures how symptoms affect individuals day-to-day life; scored from 0 to 100

  18. Global Assessment of Functioning (GAF) [ Time Frame: Change from baseline to 3-month follow-up ]
    The GAF measures how symptoms affect individuals day-to-day life; scored from 0 to 100

  19. Positive and Negative Syndrome Scale (PANSS) [ Time Frame: Change from baseline to 5 Day follow-up ]
    30 items included in the PANSS measuring positive, negative and general symptoms; 7 related to positive symptoms, 7 for negative symptoms, and 16 for general psychopathology Scale. Ranges are 7 to 49 for the Positive and Negative Scales, and 16 to 112 for the General Psychopathology Scale.

  20. Positive and Negative Syndrome Scale (PANSS) [ Time Frame: Change from baseline to 1-month follow-up ]
    30 items included in the PANSS measuring positive, negative and general symptoms; 7 related to positive symptoms, 7 for negative symptoms, and 16 for general psychopathology Scale. Ranges are 7 to 49 for the Positive and Negative Scales, and 16 to 112 for the General Psychopathology Scale.

  21. Positive and Negative Syndrome Scale (PANSS) [ Time Frame: Change from baseline to 3-month follow-up ]
    30 items included in the PANSS measuring positive, negative and general symptoms; 7 related to positive symptoms, 7 for negative symptoms, and 16 for general psychopathology Scale. Ranges are 7 to 49 for the Positive and Negative Scales, and 16 to 112 for the General Psychopathology Scale.

  22. Montgomery-Åsberg Depression Rating Scale (MADRS) [ Time Frame: Change from baseline to 5 Day follow-up ]
    The MADRS is designed to measure depression and severity of symptoms; 0 to 6 indicates no depression, 7 to 19 indicates mild depression, 20 to 34 indicates moderate depression, 35 and greater indicates severe depression.

  23. Montgomery-Åsberg Depression Rating Scale (MADRS) [ Time Frame: Change from baseline to 1-month follow-up ]
    The MADRS is designed to measure depression and severity of symptoms; 0 to 6 indicates no depression, 7 to 19 indicates mild depression, 20 to 34 indicates moderate depression, 35 and greater indicates severe depression.

  24. Montgomery-Åsberg Depression Rating Scale (MADRS) [ Time Frame: Change from baseline to 3-month follow-up ]
    The MADRS is designed to measure depression and severity of symptoms; 0 to 6 indicates no depression, 7 to 19 indicates mild depression, 20 to 34 indicates moderate depression, 35 and greater indicates severe depression.

  25. Barratt Impulsiveness Scale-11 (BIS-11) [ Time Frame: Change from baseline to 5 Day follow-up ]
    The BIS-11 is designed to assess the personality/behavioral impulsiveness. The BIS-11 has 30 items and is scored appropriately. Scored to yield a total score, three second-order factors, and six first-order factors. Each question has a 4-point scale ranging from 1 (rarely/never) to 4 (almost always/always). Higher scores mean more impulsive behavior.

  26. Barratt Impulsiveness Scale-11 (BIS-11) [ Time Frame: Change from baseline to 1-month follow-up ]
    The BIS-11 is designed to assess the personality/behavioral impulsiveness. The BIS-11 has 30 items and is scored appropriately. Scored to yield a total score, three second-order factors, and six first-order factors. Each question has a 4-point scale ranging from 1 (rarely/never) to 4 (almost always/always). Higher scores mean more impulsive behavior.

  27. Barratt Impulsiveness Scale-11 (BIS-11) [ Time Frame: Change from baseline to 3-month follow-up ]
    The BIS-11 is designed to assess the personality/behavioral impulsiveness. The BIS-11 has 30 items and is scored appropriately. Scored to yield a total score, three second-order factors, and six first-order factors. Each question has a 4-point scale ranging from 1 (rarely/never) to 4 (almost always/always). Higher scores mean more impulsive behavior.

  28. Brief Assessment of Cognition (BACS) [ Time Frame: Change from baseline to 5 Day follow-up ]
    The BACS is designed to assess several domains of cognition; Verbal Memory; Processing Speed; Working Memory; Verbal Fluency; Motor Function; Executive Functioning. Higher scores indicate better cognitive functioning.

  29. Brief Assessment of Cognition (BACS) [ Time Frame: Change from baseline to 1-month follow-up ]
    The BACS is designed to assess several domains of cognition; Verbal Memory; Processing Speed; Working Memory; Verbal Fluency; Motor Function; Executive Functioning. Higher scores indicate better cognitive functioning.

  30. Brief Assessment of Cognition (BACS) [ Time Frame: Change from baseline to 3-month follow-up ]
    The BACS is designed to assess several domains of cognition; Verbal Memory; Processing Speed; Working Memory; Verbal Fluency; Motor Function; Executive Functioning. Higher scores indicate better cognitive functioning.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05445466


Contacts
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Contact: Paulo Lizano, MD, PhD (617) 754-1227 plizano@bidmc.harvard.edu

Locations
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United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Beth Israel Deaconess Medical Center
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Responsible Party: Paulo Lizano, Assistant Professor, Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier: NCT05445466    
Other Study ID Numbers: 2022P000295
First Posted: July 6, 2022    Key Record Dates
Last Update Posted: July 6, 2022
Last Verified: June 2022

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: Yes
Keywords provided by Paulo Lizano, Beth Israel Deaconess Medical Center:
Brain Stimulation
Mania
Additional relevant MeSH terms:
Layout table for MeSH terms
Disease
Bipolar Disorder
Mood Disorders
Psychotic Disorders
Pathologic Processes
Bipolar and Related Disorders
Mental Disorders
Schizophrenia Spectrum and Other Psychotic Disorders