Clinical trial NCT05712057: Neurostimulation Versus Therapy for Problems With Emotions
Official title: Neurostimulation Enhanced Cognitive Restructuring for Transdiagnostic Emotional Dysregulation: A Component Analysis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Emotion Regulation
Mood Disorders
Stress Disorder
Anxiety Disorders
OCD
Impulse Control Disorder
Eating Disorders
Emotional Dysfunction
Emotional Instability
Emotional Distress
Emotional Maladjustment
Emotional Impulsivity
Obsessive-Compulsive Disorder
Emotion Dysregulation
Borderline Personality Disorder
Keywords: Emotion Dysregulation
Distress Intolerance
Neuromodulation
Neurostimulation
TMS
cognitive restructuring
regulation skills
neuroimaging
Emotion regulation
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2023-02-03
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Group 1 (G1) and 2 (G2) participants will receive training in cognitive restructuring, while Group 3 (G3) participants will receive training in emotional awareness. All participants will undergo negative emotion induction using autobiographical stressors. Depending on group participants could receive one of two types of neurostimulation . Randomization procedures will match subjects on: 1) severity of emotional dysregulation (high/very high), 2) sex at birth, and 3) treatment status (psychotropics/no psychotropics).
Primary purpose: TREATMENT

Brief summary: The primary goal of this clinical trial is to evaluate the unique neural and behavioral effects of a one-session training combining emotion regulation skills training, with excitatory repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (dlPFC). The secondary aim is to identify key changes in the emotion regulation neural network following the combined intervention versus each of the components alone. The third aim is to explore personalized biomarkers for response to emotion regulation training.

Participants will undergo brain imaging while engaging in an emotional regulation task. Participants will be randomly assigned to learn one of two emotion regulation skills. Participants will be reminded of recent stressors and will undergo different types of neurostimulation, targeted using fMRI (functional MRI) results. Participants who may practice their emotion regulation skills during neurostimulation in a one-time session. Following this training, participants will undergo another fMRI and an exit interview to assess for immediate neural and behavioral changes. Measures of emotion regulation will be assessed at a one week and a one month follow up visit.

Detailed description: Emotional dysregulation constitutes a serious public health problem and novel approaches are needed to effectively address it transdiagnostically. Despite rapid advancements in affective and cognitive neuroscience, there have been few attempts to translate basic findings into novel interventions. In addition, the relevance of different nodes in the emotion regulation network to psychopathology and to successful reduction of emotional arousal is not yet fully understood. Noninvasive neurostimulation, such as repetitive transcranial magnetic stimulation (rTMS), is a powerful tool with which dysfunction can be alleviated temporarily, by modulating neural activation. Therefore, the objective of the current study is to examine immediate neural and behavioral changes following neuromodulation enhanced emotion regulation training for transdiagnostic adults who report difficulties calming down when upset. The central hypothesis is that neurostimulation enhances the acquisition of emotion regulation skills and leads to remediated neural function in the emotion regulation network. The investigators' long-term goal is to develop novel interventions that harness neuroscientific findings to advance behavioral treatments.

The primary aim of this project is to evaluate the unique neural and behavioral effects of a one-session training combining emotion regulation skills with excitatory neurostimulation over the dorsolateral prefrontal cortex (dlPFC). The secondary aim is to identify key changes in the emotion regulation neural network following the combined intervention versus each of the components alone. The third aim is to explore personalized biomarkers for response to emotion regulation training. To achieve these aims, 240 rTMS naïve, community adults who meet criteria for a DSM-5 disorders (excluding if co-occurring anorexia, moderate to severe alcohol and substance use, bipolar I, or psychotic disorders) and who self-report high emotional dysregulation will participate in brain imaging while undergoing an emotional regulation task. Both structural and functional MRI (fMRI) images will be collected. Participants will be randomly assigned to one of three experimental groups that blend neurostimulation and behavioral skills training in different ways. Participants will be reminded of recent autobiographical stressors and will undergo different types of neurostimulation, targeted using fMRI results. Physiological arousal will be monitored throughout the experimental visit. Following this training, 1 week later, participants will undergo another functional scan to assess for immediate neural and behavioral changes. Bio-behavioral measures of emotion regulation will be assessed at this one week visit. The 1-month follow up will occur 1 month after the one week follow-up visit. At this final follow-up visit, participants will also complete an exit interview that assesses acceptability and expectancies as well as a battery of self reports. One final set of bio-behavioral measures of emotion regulation will be completed as well. If successful, the investigators' line of research will provide key mechanistic information to develop a novel transdiagnostic treatment for DSM-5 disorders.

Eligibility criteria: Inclusion Criteria:

* age 18 to 55
* elevated overall score on Difficulties with Emotion Regulation Scale (DERS total score \>=90)
* has been in the same type of psychotherapy (including none) for the last 4 weeks/1mo (\*except for current CBT) and is willing to stay on the same regimen throughout the study.
* low self-reported use of cognitive restructuring (ERQ restructuring subscale average score \< 4.7)
* meets criteria for at least one mood (including Bipolar II w/o current hypomania), anxiety, stressor, OCD, Impulse Control, ADHD, or eating DSM-5 disorder (except exclusionary diagnoses such as severe anorexia). Note: Both current or partial remission of the disorder will be ok for inclusion into the study.
* verbal agreement to maintain dose of prescribed psychotropic medication (if any) constant throughout the study, provided they are stable on it for the past 4 weeks (except exclusion medication and except if there is a medical emergency requiring changes in medication).
* Naïve to rTMS

Exclusion Criteria:

* current hypomania (Note: Bipolar II w/o current hypomanic episode is ok for inclusion)
* meets diagnostic criteria for current or history of psychotic disorder, or psychotic features,
* meets diagnostic criteria for Bipolar I disorder
* meets diagnostic criteria on SCID5 for current alcohol or substance use disorder (moderate and high severity) or meets past history of severe alcohol use disorder
* unable to read, blind, or deaf, or unwilling to give consent
* non-English speaker,
* verbal IQ \< 90 on the North American Adult Reading Test (NART).
* current uncontrolled anorexia or other condition requiring hospitalization
* high risk for suicide defined as either having attempted suicide in past 6 months or reporting current suicidal ideation that includes a method, plan, or intent to die
* current serious medical illness, including current severe migraine headaches
* started/changed psychotropic medications in the prior 4 weeks, or plans to change medication during the study
* history of seizure except those therapeutically induced by ECT (childhood febrile seizures are acceptable and these subjects may be included in the study), history of epilepsy in self or first degree relatives, stroke, brain surgery, head injury, cranial metal implants, known structural brain lesion, devices that may be affected by TMS (pacemaker, medication pump, cochlear implant, implanted brain stimulator), have left elbow/hand/wrist tendonitis
* conditions associated with increased intracranial pressure, space occupying brain lesion, transient ischemic attack, cerebral aneurysm, dementia, Parkinson's or Huntington's disease, multiple sclerosis
* Wellbutrin \>300mg per day or on daily stimulant/ADHD medications above the recommended FDA daily recommendations
* use of investigational drug or devices within 4 weeks of screening
* cochlear implants
* Pregnancy
* metal in body that would exclude them from the MRI scan; severe claustrophobia
* is a prisoner or in police custody at time of screening, or has pending court case jeopardizing the participation in the study
* has had TMS in their lifetime
* has had CBT in the past 4 weeks or plans to start therapy during the study
* weighs over 300 pounds (could not fit in MRI scanner)

Primary outcomes:
measure: High Frequency Heart Rate Variability (HF-HRV) during regulation blocks during the neurostimulation day
timeFrame: Within a month of the initial assessment
measure: Time to return to Heart Rate (HR) baseline measured during regulation period
timeFrame: Within a month of the initial assessment
measure: Change in the ventrolateral prefrontal cortex (vlPFC) for the [restructure-flow_negative] contrast
timeFrame: baseline Neuroimaging Scan vs post Neuroimaging scan (1 week follow-up post neurostimulation)
measure: Change in the dorsomedial prefrontal cortex (dmPFC) for the [restructure-flow_negative] contrast
timeFrame: baseline Neuroimaging Scan, post Neuroimaging Scan (1 week follow-up post neurostimulation)
measure: Change in the ventromedial prefrontal cortex (vmPFC) for the [restructure-flow_negative] contrast
timeFrame: baseline Neuroimaging Scan, post Neuroimaging Scan (1 week follow-up post neurostimulation)
measure: Change in the insular cortex for the [restructure-flow_negative] contrast
timeFrame: baseline Neuroimaging Scan, post Neuroimaging Scan (1 week follow-up post neurostimulation)
measure: Change in dorsolateral prefrontal cortex (dlPFC)-insula connectivity during [restructure - flow_negative]
timeFrame: baseline Neuroimaging Scan, post Neuroimaging Scan (1 week follow-up post neurostimulation)
measure: Change in dorsolateral prefrontal cortex (dlPFC)-amygdala connectivity during [restructure - flow_negative]
timeFrame: baseline Neuroimaging Scan, post Neuroimaging Scan (1 week follow-up post neurostimulation)
Secondary outcomes:
measure: Difficulties in Emotion Regulation Scale (DERS) self-report change
timeFrame: Baseline, 1 week follow-up after neurostimulation, 1 month follow-up
measure: Emotion Regulation Questionnaire (ERQ) self-report change
timeFrame: Baseline, 1 week follow-up after neurostimulation, 1 month follow-up
measure: Change in the dlPFC for the [restructure - flow_negative] contrast
timeFrame: baseline Neuroimaging scan, post Neuroimaging Scan (1 week follow-up neurostimulation)
measure: Change in the amygdala for the [restructure - flow_negative] contrast
timeFrame: baseline Neuroimaging scan, post Neuroimaging Scan (1 week follow-up neurostimulation)
measure: Outcome Questionnaire (OQ-45) self-report change
timeFrame: Baseline, 1 week follow-up after neurostimulation, 1 month follow-up
measure: Cognitive Skills Questionnaire (CSQ) self-report change
timeFrame: Baseline, 1 week follow-up after neurostimulation, 1 month follow-up
measure: Self Efficacy with Emotion Regulation (PROMIS-SEME)
timeFrame: Baseline, 1 week follow-up after neurostimulation, 1 month follow-up
measure: Change in subjective units of distress (SUDS)
timeFrame: Neurostimulation visit (which will occur within a month of the initial assessment)
measure: HF-HRV during regulation block at follow up
timeFrame: one week follow-up, 1 month follow-up
measure: Time to return to HR baseline measured during regulation period at follow up
timeFrame: one week follow-up, 1 month follow-up
Other outcomes:
measure: Change in vmPFC-insula connectivity during [restructure - flow_negative]
timeFrame: baseline Neuroimaging scan, post Neuroimaging Scan (1 week follow-up neurostimulation)
measure: Cognitive flexibility inventory (CFI) and cognitive control and flexibility inventory (CCFI)
timeFrame: Baseline
measure: Wisconsin Card Sorting Task
timeFrame: Baseline
measure: Affect Intensity Measure (AIM)
timeFrame: Baseline
Locations:
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
Study officials:
affiliation: Duke University
name: Andrada D Neacsiu, PhD
role: PRINCIPAL_INVESTIGATOR
References: