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Accelerated Theta Burst Stimulation for Inpatients With Bipolar Disorder

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ClinicalTrials.gov Identifier: NCT04058249
Recruitment Status : Not yet recruiting
First Posted : August 15, 2019
Last Update Posted : August 15, 2019
Sponsor:
Information provided by (Responsible Party):
Nolan R, Stanford University

Brief Summary:
This study evaluates the efficacy of an accelerated schedule of theta-burst stimulation for bipolar disorder. In this open-label study, all participants will receive accelerated theta-burst stimulation.

Condition or disease Intervention/treatment Phase
Bipolar Disorder, Manic Bipolar Disorder I Bipolar II Disorder Device: Accelerated intermittent theta-burst stimulation over right DLPFC Not Applicable

Detailed Description:
Repetitive transcranial magnetic stimulation (rTMS) is an established technology as therapy for treatment-resistant depression. The approved method for treatment is 10Hz stimulation for 40 minutes over the left dorsolateral prefrontal cortex (L-DLPFC). This methodology has been very successful in real-world situations. The limitations of this approach include the duration of the treatment (approximately 40 minutes per treatment session over 4-6 weeks). Recently, researchers have modified the treatment parameters to reduce treatment times with some preliminary success. In a recent study, an accelerated paradigm showed a significant antidepressant effect (90% remission rate) in individuals with treatment-resistant depression (TRD), in only 5 days . Additionally, 5 participants from this study carried a bipolar diagnosis and responded equally as well, with no adverse events experienced or manic/hypomanic conversion observed during the treatment series. This study intends to further modify the parameters to create a more rapid form of this treatment for bipolar disorder and look at the change in clinical measures and neuroimaging biomarkers.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Accelerated Theta Burst Stimulation for Inpatients With Bipolar Disorder
Estimated Study Start Date : November 1, 2019
Estimated Primary Completion Date : December 1, 2022
Estimated Study Completion Date : December 1, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bipolar Disorder

Arm Intervention/treatment
Experimental: Right DLPFC aiTBS stimulation Device: Accelerated intermittent theta-burst stimulation over right DLPFC

All participants will receive accelerated intermittent theta-burst stimulation to the right DLPFC. Stimulation intensity will be standardized at 90% of resting motor threshold adjust to the skull to cortical surface distance.

Stimulation will be delivered to right-DLPFC using the Brainsway stimulator.





Primary Outcome Measures :
  1. Change from baseline Young Mania Rating Scale (YMRS) [ Time Frame: Baseline and immediate post-treatment ]

    The Young Mania Rating Scale (YMRS) is one of the most frequently utilized rating scales to assess manic symptoms. The scale has 11 items and is based on the patient's subjective report of his or her clinical condition.

    There are four items that are graded on a 0 to 8 scale (irritability, speech, thought content, and disruptive/aggressive behavior), while the remaining seven items are graded on a 0 to 4 scale. These four items are given twice the weight of the others to compensate for poor cooperation from severely ill patients.

    Typical YMRS baseline scores can vary a lot. They depend on the patients' clinical features such as mania (YMRS = 12), depression (YMRS = 3), or euthymia (YMRS = 2).



Secondary Outcome Measures :
  1. Change from baseline Montgomery Asberg Depression Rating Scale (MADRS) [ Time Frame: Baseline and immediate post-treatment ]

    A ten item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders.

    The MADRS uses a 0 to 6 severity scale, scored following the interview. Scoring/Interpretation: Higher scores indicate increasing depressive symptoms. ... Cut-off points include: 0 to 6 - symptom absent, 7 to 19 - mild depression, 30 to 34 - moderate, 35 to 60 - severe depression.


  2. Change from baseline functional connectivity as measured by MR imaging [ Time Frame: Baseline and immediate post-treatment ]
    Pre- and post resting state functional connectivity and structural T1-weighted MRI scans to determine the anti-correlated LDLPFC and SCC treatment location. The identified cluster with the greatest anti-correlation between the LDLPFC and SCC will have been utilized for the targeted aiTBS treatment. This algorithm will have also been applied to the post-imaging sessions to give measurements of voxel-wise blood flow in this anti-correlation targeted brain ROI.

  3. Change from baseline Hamilton Rating Scale for Depression (HAM-6) [ Time Frame: Baseline and immediate post-treatment ]
    A 6-item clinical assessment measuring depressive symptoms. Scores range from 0-24 with scores >5 indicating clinical levels of depressive symptoms.

  4. Change from baseline Beck Depression Inventory (BDI-II) [ Time Frame: Baseline and immediate post-treatment ]

    The Beck Depression Inventory (BDI-II) is a 21-item, self-report rating inventory that measures characteristic attitudes and symptoms of depression. BDI-II items are rated on a 4-point scale ranging from 0 to 3 based on severity of each item. The maximum total score is 63.

    Scores: 0-13= minimal depression, 14-19=mild depression, 20-28=moderate depression, 29-63=severe depression


  5. Change in Scale of Suicidal Ideation (SSI) score [ Time Frame: Baseline and immediate post-treatment ]

    19-item clinician administered assessment to measure the intensity, pervasiveness, and characteristics of suicidal ideation in adults.

    Scores range from 0-38, with a score higher than 6, indicating active suicidal ideation.


  6. Change in baseline Altman Self-Rating Mania Scale (ASRM) [ Time Frame: Baseline and immediate post-treatment ]

    The ASRM is a 5-item self rating mania scale, designed to assess the presence and/or severity of manic symptoms.

    Interpretation:

    A score of 6 or higher indicates a high probability of a manic or hypomanic condition A score of 6 or higher may indicate a need for treatment and/or further diagnostic workup A score of 5 or lower is less likely to be associated with significant symptoms of mania


  7. Change from baseline Internal State Scale (ISS) [ Time Frame: Baseline and immediate post-treatment ]

    Independent assessment of manic and depressive symptoms by self- rating scale characteristics and implications for the study of mania.

    The ISS contains a series of visual analogue scale (VAS) items consisting of statement followed by a by eleven "bins" (equivalent to 0-10, 11-20, …91-100). In Likert-based scoring, the first bin is scored as zero, the second as 10, and so on to theeleventh bin which is scored as 100.

    Scoring:

    >155: (Hypo)Mania >155: Mixed State <155: Euthymia <155: Depression


  8. Change in NIH Cognitive Toolbox performance [ Time Frame: Baseline and immediate post-treatment ]
    Neurocognitive assessments delivered through an iPad app

  9. Change in heart rate variability [ Time Frame: Baseline and immediate post-treatment ]
    Polar H10 heart rate monitor will be used to measure heart rate variability

  10. Change in Temporal Experience of Pleasure Scale (TEPS) [ Time Frame: Baseline and immediate post-treatment ]

    The Temporal Experience of Pleasure Scale (TEPS) is a measure specifically designed to capture the anticipatory and consummatory facets of pleasure.

    TEPS is an 18-item questionnaire. Each item is scored from 0 "very false for me" to 6 "very true for me". Total score ranges from 0 to 108.


  11. Change in the Quality of Life Enjoyment and Satisfaction Questionnaire-short form score (Q-LES-Q-SF) [ Time Frame: Baseline and immediate post-treatment ]

    15-item self-report questionnaire where each item is scored from very poor=1 to very good=5.

    The scoring of the Q-LES-Q-SF involves summing only the first 14 items to yield a raw total score.

    The last two items are not included in the total score but are stand-alone items.

    The raw total score ranges from 14 (min) to 70 (max).


  12. Biomarker analysis in patient blood samples [ Time Frame: Baseline and immediate post-treatment ]
    Blood (plasma, DNA, RNA) samples will be collected before and immediately after treatment to identify changes in potential biomarkers of mania/hypomania and treatment response such as inflammatory cytokines. This analysis is exploratory.

  13. Saliva cortisol levels [ Time Frame: Baseline and immediate post-treatment ]

    Saliva samples will be collected before and immediately after after stimulation. Saliva collection is performed by registered study personnel.

    Saliva samples will be analyzed by our collaborators at the Open Medicine Institute. Specifically, saliva samples will be analyzed for cortisol levels.


  14. Biomarker analysis in patient stool samples [ Time Frame: Baseline and immediate post-treatment ]

    Stool samples will be collected before and immediately after stimulation. Stool collection is performed by registered hospital nurses.

    Stool samples will be analyzed by our collaborators at the Open Medicine Institute. Microbiota composition e.g. Clostridium, Bacteroides, and Prevotella levels will be analyzed as microbiota influences individual differences in health and disease including psychiatric disorders.

    All analyses of stool samples will be conducted in the Open Medicine Institute.


  15. Change in resting-state recordings and TMS-evoked potentials in EEG data. [ Time Frame: Baseline and immediate post-treatment ]
    EEG recordings will be made before and after the treatment course to differences in EEG data associated with hypomania/mania and treatment response (e.g. amplitude & latency of tms-evoked potentials (TEPs), spatio-temporal distribution of TEPs and resting-state connectivity)

  16. Change in Columbia Suicide Severity Rating Scale (C-CSSRS), self-report version [ Time Frame: Baseline and immediate post-treatment ]

    A self-report measure of the Columbia Suicide Severity Rating Scale (C-CSSRS). This questionnaire was developed to rate suicidal ideation and behavior.

    It rates a person's degree of suicidal ideation on a scale, ranging from "wish to be dead" to "active suicidal ideation with specific plan and intent and behaviors.

    The scale identifies specific behaviors which may be indicative of a person's intent to complete suicide. An person exhibiting even a single behavior identified by the scale was 8 to 10 times more likely to complete suicide.




Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Participants aged 18yo-80yo with a primary diagnosis of bipolar I or II disorder in a current hypomanic/manic episode or bipolar affective disorder II in a current hypomanic/manic episode.
  2. Able to read, understand, and provide written, dated informed consent prior to screening. Participants will be deemed likely to comply with study protocol and communicate with study personnel about adverse events and other clinically important information.
  3. Currently experiencing a hypomanic/manic episode according to the criteria defined in the Diagnosis and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR)
  4. Meet the threshold on the total HAMD17 score of >/=20 prior to aiTBS.
  5. Meet the threshold on the BDI-II score of >/=17 prior to aiTBS.
  6. Not currently experiencing psychosis (MINI)

8. Must have a stable psychiatrist during study enrollment

9. Must be on a mood stabilizer regimen

12. Meet the threshold on the MADRS, with a total score of >/=20 prior to aiTBS.

13. History of ECT intolerance or exposure is permitted.

Exclusion Criteria:

  1. Any structural lesion e.g. structural neurological condition, more subcortical lesions than would be expected for age, stroke effecting stimulated area or connected areas or any other clinically significant abnormality that might affect safety, study participation, or confound interpretation of study results.
  2. Metal implant in brain (e.g. deep brain stimulation), cardiac pacemaker, or cochlear implants
  3. History of epilepsy/ seizures (including history of withdrawal/ provoked seizures)
  4. Shrapnel or any ferromagnetic item in the head
  5. Pregnancy
  6. Autism Spectrum disorder
  7. Any current or past history of any physical condition which in the investigator's opinion might put the subject at risk or interfere with study results interpretation
  8. Active substance abuse (<1 week) or intoxication verified by toxicology screen--of cocaine, amphetamines, benzodiazepines
  9. Cognitive impairment (including dementia)
  10. Current severe insomnia (must sleep a minimum of 5 hours the night before stimulation)
  11. Current psychosis
  12. Showing symptoms of withdrawal from alcohol or benzodiazepines
  13. IQ<70
  14. Parkinsonism or other movement d/o determined by PI to interfere with treatment
  15. Any other indication the PI feels would comprise data.
  16. A diagnosis of obsessive-compulsive disorder (OCD)
  17. Any history of psycho surgery for depression
  18. Any history of myocardial infarction, CABG, CHF, or other cardiac history
  19. The presence or diagnosis of prominent anxiety disorder, personality disorder or dysthymia
  20. History of intractable migraine

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): NCT04058249


Contacts
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Contact: Romina Nejad, MSc 650-497-3933 rnejad@stanford.edu

Locations
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United States, California
Stanford Hospital Not yet recruiting
Palo Alto, California, United States, 94304
Contact: Nolan R Williams, MD       nolanw@stanford.edu   
Sponsors and Collaborators
Stanford University

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Responsible Party: Nolan R, Dr Nolan Williams, Assistant Professor, Stanford University
ClinicalTrials.gov Identifier: NCT04058249     History of Changes
Other Study ID Numbers: 52635
First Posted: August 15, 2019    Key Record Dates
Last Update Posted: August 15, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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: No
Pediatric Postmarket Surveillance of a Device Product: No
Additional relevant MeSH terms:
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Disease
Bipolar Disorder
Pathologic Processes
Bipolar and Related Disorders
Mental Disorders