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Neuromodulation for Enhancement of Emotion Regulation in Bipolar Mood Disorders

Primary Purpose

Bipolar Disorder

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Transcranial Magnetic Stimulation
Sponsored by
Massachusetts General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Bipolar Disorder focused on measuring Transcranial Magnetic Stimulation, Emotion Regulation

Eligibility Criteria

22 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria (Healthy Controls)

  1. Male or female age 18-55
  2. No history of psychiatric disorder, as assessed using the Mini-International Neuropsychiatric Interview (MINI).
  3. Non-Clinical Levels of Emotion Dysregulation, as assessed using the Difficulties in Emotion Regulation Scale (DERS) Non-clinical levels of emotion dysregulation will be defined as a score < 80 on the DERS.

Exclusion Criteria (Healthy Controls)

  1. Current or history of psychiatric disorders
  2. Endorsement of clinical levels of emotion dysregulation
  3. Current or history of: organic mental disorder; substance abuse within the past 12 months and/or history of substance abuse for > 1 year; past or current substance dependence (including alcohol); schizophrenia; delusional disorder; and psychotic disorders.
  4. Current pregnancy.
  5. Medical illness or non-psychiatric medical treatment that would likely interfere with study participation
  6. Neurologic disorder, prior neurosurgical procedure, prior electroconvulsive therapy (ECT) or TMS, history of seizures or head trauma.
  7. Presence of metallic implants that would interfere with safety during fMRI scanning.

Inclusion Criteria (Bipolar Disorder Group)

  1. Male or female age 18-55
  2. Diagnosis of Bipolar I Disorder (BD-I), as assessed through MINI.

  3. Current mood state euthymic.

    a. Hamilton-Depression Rating Scale (HAM-D-17) and Young Mania Rating Scale (YMRS) will be used to assess current depressive and manic symptoms. Euthymia will be defined as a HAM-D-17 score <10 and YMRS score <12.

  4. Clinical Levels of Emotion Dysregulation, as assessed using the DERS. Clinical levels of emotion dysregulation will be defined as a score > 80 on the DERS.

Exclusion Criteria (Bipolar Disorder Group)

  1. Current symptoms of mania or depression (YMRS score >12, HAM-D-17 score >10).
  2. Medication instability (<3 months).
  3. Current or history of: organic mental disorder; substance abuse within the past 12 months and/or history of substance abuse for > 1 year; past or current substance dependence (including alcohol), verified by urine toxicology screen; schizophrenia; delusional disorder; and psychotic disorders.
  4. Current pregnancy.
  5. Medical illness or non-psychiatric medical treatment that would likely interfere with study participation
  6. Neurologic disorder, prior neurosurgical procedure, prior ECT or TMS, history of seizures or head trauma.
  7. Presence of metallic implants that would interfere with safety during fMRI scanning.

Sites / Locations

  • Martinos Center for Biomedical ImagingRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Experimental

Arm Label

Healthy Control

Bipolar Group

Arm Description

This group consists of individuals with no psychiatric diagnosis.

This group consists of individuals with a diagnosis of bipolar disorder who have been randomized to receive high-dose TMS (i.e., 1800 pulses) and sham TMS.

Outcomes

Primary Outcome Measures

Multisource Interference Task with International Affective Pictures Set (MSIT-IAPS)
The MSIT-IAPS task is a well-validated fMRI task designed to assess the effects of emotional distractors on cognitive control. During each trial, a three-digit number is presented. Each set contains two identical distractor numbers and a target number that differed from the distractors. Participants report via a button press the identity of the target number that differs from the two distractor numbers. Noninterference (control) trials: distractor numbers are always zeros, and the identity of the target number always corresponds to its position on the button response pad (100, 020, 003). Interference trials: distractor numbers are always numbers other than 0, and the identity of the target number is always incongruent with its position on the button response pad (e.g. 211, 232, 331, etc.). Each trial of the MSIT is overlaid on a negative, positive, or neutral IAPS image. Reaction time (ms) and accuracy (% correct) is calculated for each trial.
Emotion Conflict Resolution Task
The ECR task is a well-validated task designed to assess the effects of emotional conflict that arises from the incompatibility between task-relevant and task-irrelevant emotional dimensions of a stimulus. Faces with fearful and happy expressions are presented with the words "happy" or "fear" written across them. Words are either congruent (e.g. "happy" written across an image with a happy expression) or incongruent (e.g. "happy" written across an image with a fearful expression). Subjects are asked to identify the emotional expression of the face while ignoring the word. Trials are analyzed with regard to immediately preceding trials: incongruent trials preceded by congruent trials (CI trials) measure emotion conflict, and incongruent trials preceded by incongruent trials (II trials) measure resolution of emotion conflict. Reaction time (ms) and accuracy (% correct) is calculated for each trial.

Secondary Outcome Measures

MSIT-IAPS Task-induced blood oxygen level dependent (BOLD) signal
Task-dependent linear time course (ß-value) of BOLD signal during performance of MSIT-IAPS task. Differences in ß-values during relevant task conditions (CI versus II) are compared.
MSIT-IAPS Task-induced blood oxygen level dependent (BOLD) signal functional connectivity
Task-dependent BOLD signal correlation strengths (z-transformed values) during performance of the task. Differences in z-transformed values during relevant task conditions (CI versus II) are compared.
ECR Task-induced blood oxygen level dependent (BOLD) signal
Task-dependent linear time course (ß-value) of BOLD signal during performance of the Cognitive Reappraisal task. Differences in ß-values during relevant task conditions (Reappraise versus Attend) are compared.
ECR Task-induced blood oxygen level dependent (BOLD) signal functional connectivity
Task-dependent BOLD signal correlation strengths (z-transformed values) during performance of the Cognitive Reappraisal task. Differences in ztransformed values during relevant task conditions (Reappraise versus Attend) are compared.
Skin Conductance Response
Skin conductance response is measured by recording electrodermal skin response using electrode sensors applied to fingertips. Correlation between changes in skin conductance response and changes in task performance (RT, distress ratings) are examined as a task manipulation check.

Full Information

First Posted
February 20, 2020
Last Updated
October 5, 2023
Sponsor
Massachusetts General Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT04284267
Brief Title
Neuromodulation for Enhancement of Emotion Regulation in Bipolar Mood Disorders
Official Title
Neuromodulation for Enhancement of Emotion Regulation in Bipolar Mood Disorders
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 1, 2021 (Actual)
Primary Completion Date
January 1, 2025 (Anticipated)
Study Completion Date
April 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The investigators are conducting this research study to better understand how individuals with bipolar disorder regulate their emotions, and if transcranial magnetic stimulation (TMS) can help improve emotion regulation for individuals with bipolar mood disorders.
Detailed Description
The objective of this study protocol is to test whether intermittent theta-burst transcranial magnetic stimulation (iTBS-TMS) to ventrolateral prefrontal cortex (VLPFC) or inferior parietal lobule (IPL) can improve performance on emotion regulation tasks in patients with bipolar disorder. Results from this study will help inform future treatment development to improve emotion regulation in patients with bipolar disorder. The study will proceed in two phases: During Phase 1, a cohort of 30 healthy control subjects will be recruited in order to establish a normative sample from which to compare patient data. Functional magnetic resonance imaging (fMRI) data will be collected from healthy control participants during performance on two emotion regulation tasks (probing implicit and explicit emotion regulation). Data from these subjects will provide a normative distribution of VLPFC and IPL function from which to compare individual patients. During Phase 2, a cohort of 30 patients diagnosed with bipolar disorder will be recruited. Patient participants will perform the same two emotion regulation tasks during fMRI scanning. Data from individual patients will be analyzed to detect specific VLPFC and IPL subregions showing activation deviations from healthy controls (Phase 1 data). Patient-specific VLPFC and IPL subregions showing patterns of activation greater than two standard deviations from healthy controls will be used as individualized target sites for TMS stimulation. Patients will then receive high-dose iTBS-TMS (1800 pulses) of the VLPFC and IPL, and sham iTBS-TMS to the dorsomedial prefrontal cortex (dmPFC) across three separate study visits. Order of target stimulation will be randomized across participants. TMS sessions will take approximately 10 minutes and will be immediately followed by an fMRI scanning session, during which participants will again complete the implicit and explicit emotion regulation tasks. TMS sessions will take place in the scanning bay to enable quick transition to the fMRI task. Baseline scanning sessions and either active TMS-fMRI or sham TMS-fMRI sessions will occur on separate days, no more than two weeks apart. Effects of iTBS-TMS on emotion regulation will be evaluated by comparing pre-TMS versus post-TMS behavior, neural activation, and functional connectivity patterns during performance on implicit and explicit emotion regulation tasks.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bipolar Disorder
Keywords
Transcranial Magnetic Stimulation, Emotion Regulation

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Factorial Assignment
Model Description
There will be a healthy control group and a bipolar disorder group. The bipolar disorder group will then be randomized to one of three conditions.
Masking
Participant
Masking Description
Masking will be implemented using a active-placebo TMS coil.
Allocation
Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Healthy Control
Arm Type
No Intervention
Arm Description
This group consists of individuals with no psychiatric diagnosis.
Arm Title
Bipolar Group
Arm Type
Experimental
Arm Description
This group consists of individuals with a diagnosis of bipolar disorder who have been randomized to receive high-dose TMS (i.e., 1800 pulses) and sham TMS.
Intervention Type
Device
Intervention Name(s)
Transcranial Magnetic Stimulation
Other Intervention Name(s)
TMS
Intervention Description
TMS is a non-invasive tool for modulating patterns of brain activation and circuit connectivity. It uses electromagnetic pulses to induce electric currents over the cortex that serve to depolarize or hyperpolarize neurons, thereby changing patterns of synaptic activity. This study will use intermittent theta burst stimulation (iTBS), an efficient TMS protocol that uses high frequency (50Hz) triplets of TMS given every 200 milliseconds (i.e. at 5 Hz).
Primary Outcome Measure Information:
Title
Multisource Interference Task with International Affective Pictures Set (MSIT-IAPS)
Description
The MSIT-IAPS task is a well-validated fMRI task designed to assess the effects of emotional distractors on cognitive control. During each trial, a three-digit number is presented. Each set contains two identical distractor numbers and a target number that differed from the distractors. Participants report via a button press the identity of the target number that differs from the two distractor numbers. Noninterference (control) trials: distractor numbers are always zeros, and the identity of the target number always corresponds to its position on the button response pad (100, 020, 003). Interference trials: distractor numbers are always numbers other than 0, and the identity of the target number is always incongruent with its position on the button response pad (e.g. 211, 232, 331, etc.). Each trial of the MSIT is overlaid on a negative, positive, or neutral IAPS image. Reaction time (ms) and accuracy (% correct) is calculated for each trial.
Time Frame
Change from Baseline to Post-TMS Stimulation (30 min-1 hour)
Title
Emotion Conflict Resolution Task
Description
The ECR task is a well-validated task designed to assess the effects of emotional conflict that arises from the incompatibility between task-relevant and task-irrelevant emotional dimensions of a stimulus. Faces with fearful and happy expressions are presented with the words "happy" or "fear" written across them. Words are either congruent (e.g. "happy" written across an image with a happy expression) or incongruent (e.g. "happy" written across an image with a fearful expression). Subjects are asked to identify the emotional expression of the face while ignoring the word. Trials are analyzed with regard to immediately preceding trials: incongruent trials preceded by congruent trials (CI trials) measure emotion conflict, and incongruent trials preceded by incongruent trials (II trials) measure resolution of emotion conflict. Reaction time (ms) and accuracy (% correct) is calculated for each trial.
Time Frame
Change from Baseline to Post-TMS Stimulation (30 min-1 hour)
Secondary Outcome Measure Information:
Title
MSIT-IAPS Task-induced blood oxygen level dependent (BOLD) signal
Description
Task-dependent linear time course (ß-value) of BOLD signal during performance of MSIT-IAPS task. Differences in ß-values during relevant task conditions (CI versus II) are compared.
Time Frame
Change from Baseline to Post-TMS Stimulation (30 min-1 hour)
Title
MSIT-IAPS Task-induced blood oxygen level dependent (BOLD) signal functional connectivity
Description
Task-dependent BOLD signal correlation strengths (z-transformed values) during performance of the task. Differences in z-transformed values during relevant task conditions (CI versus II) are compared.
Time Frame
Change from Baseline to Post-TMS Stimulation (30 min-1 hour)
Title
ECR Task-induced blood oxygen level dependent (BOLD) signal
Description
Task-dependent linear time course (ß-value) of BOLD signal during performance of the Cognitive Reappraisal task. Differences in ß-values during relevant task conditions (Reappraise versus Attend) are compared.
Time Frame
Change from Baseline to Post-TMS Stimulation (30 min-1 hour)
Title
ECR Task-induced blood oxygen level dependent (BOLD) signal functional connectivity
Description
Task-dependent BOLD signal correlation strengths (z-transformed values) during performance of the Cognitive Reappraisal task. Differences in ztransformed values during relevant task conditions (Reappraise versus Attend) are compared.
Time Frame
Change from Baseline to Post-TMS Stimulation (30 min-1 hour)
Title
Skin Conductance Response
Description
Skin conductance response is measured by recording electrodermal skin response using electrode sensors applied to fingertips. Correlation between changes in skin conductance response and changes in task performance (RT, distress ratings) are examined as a task manipulation check.
Time Frame
Change from Baseline to Post-TMS Stimulation (30 min-1 hour)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
22 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria (Healthy Controls) Male or female age 18-55 No history of psychiatric disorder, as assessed using the Mini-International Neuropsychiatric Interview (MINI). Non-Clinical Levels of Emotion Dysregulation, as assessed using the Difficulties in Emotion Regulation Scale (DERS) Non-clinical levels of emotion dysregulation will be defined as a score < 80 on the DERS. Exclusion Criteria (Healthy Controls) Current or history of psychiatric disorders Endorsement of clinical levels of emotion dysregulation Current or history of: organic mental disorder; substance abuse within the past 12 months and/or history of substance abuse for > 1 year; past or current substance dependence (including alcohol); schizophrenia; delusional disorder; and psychotic disorders. Current pregnancy. Medical illness or non-psychiatric medical treatment that would likely interfere with study participation Neurologic disorder, prior neurosurgical procedure, prior electroconvulsive therapy (ECT) or TMS, history of seizures or head trauma. Presence of metallic implants that would interfere with safety during fMRI scanning. Inclusion Criteria (Bipolar Disorder Group) Male or female age 18-55 Diagnosis of Bipolar I Disorder (BD-I), as assessed through MINI. Current mood state euthymic. a. Hamilton-Depression Rating Scale (HAM-D-17) and Young Mania Rating Scale (YMRS) will be used to assess current depressive and manic symptoms. Euthymia will be defined as a HAM-D-17 score <10 and YMRS score <12. Clinical Levels of Emotion Dysregulation, as assessed using the DERS. Clinical levels of emotion dysregulation will be defined as a score > 80 on the DERS. Exclusion Criteria (Bipolar Disorder Group) Current symptoms of mania or depression (YMRS score >12, HAM-D-17 score >10). Medication instability (<3 months). Current or history of: organic mental disorder; substance abuse within the past 12 months and/or history of substance abuse for > 1 year; past or current substance dependence (including alcohol), verified by urine toxicology screen; schizophrenia; delusional disorder; and psychotic disorders. Current pregnancy. Medical illness or non-psychiatric medical treatment that would likely interfere with study participation Neurologic disorder, prior neurosurgical procedure, prior ECT or TMS, history of seizures or head trauma. Presence of metallic implants that would interfere with safety during fMRI scanning.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Alexis Worthley, BA
Phone
6177248780
Email
er-studies@mgh.harvard.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Blake Andreou, BA
Phone
6177248780
Email
er-studies@mgh.harvard.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kristen Ellard, PhD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Martinos Center for Biomedical Imaging
City
Charlestown
State/Province
Massachusetts
ZIP/Postal Code
02129
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kristen K Ellard, PhD
Phone
617-724-3221
Email
kellard@mgh.harvard.edu
First Name & Middle Initial & Last Name & Degree
Kristen K Ellard, PhD

12. IPD Sharing Statement

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Neuromodulation for Enhancement of Emotion Regulation in Bipolar Mood Disorders

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