NCT05712057

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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
240

participants targeted

Target at P75+ for not_applicable

Timeline
19mo left

Started May 2023

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress66%
May 2023Dec 2027

First Submitted

Initial submission to the registry

January 12, 2023

Completed
22 days until next milestone

First Posted

Study publicly available on registry

February 3, 2023

Completed
3 months until next milestone

Study Start

First participant enrolled

May 15, 2023

Completed
4.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 31, 2027

Expected
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2027

Last Updated

March 4, 2026

Status Verified

March 1, 2026

Enrollment Period

4.5 years

First QC Date

January 12, 2023

Last Update Submit

March 2, 2026

Conditions

Keywords

Emotion DysregulationDistress IntoleranceNeuromodulationNeurostimulationTMScognitive restructuringregulation skillsneuroimagingEmotion regulation

Outcome Measures

Primary Outcomes (8)

  • High Frequency Heart Rate Variability (HF-HRV) during regulation blocks during the neurostimulation day

    Calculation of physiological data High frequency HRV (HF-HRV) during regulation blocks during the neurostimulation day accounting for baseline controlling for baseline HF-HRV

    Within a month of the initial assessment

  • Time to return to Heart Rate (HR) baseline measured during regulation period

    Following each negative mood induction during the neurostimulation experiment, the time it takes to return baseline HR will be calculated for each of the three regulation periods.

    Within a month of the initial assessment

  • Change in the ventrolateral prefrontal cortex (vlPFC) for the [restructure-flow_negative] contrast

    Change in the maximum activation in the vlPFC from pre-post neuroimaging in the contrast of interest

    baseline Neuroimaging Scan vs post Neuroimaging scan (1 week follow-up post neurostimulation)

  • Change in the dorsomedial prefrontal cortex (dmPFC) for the [restructure-flow_negative] contrast

    Change in the maximum activation in the dmPFC from pre-post neuroimaging in the contrast of interest

    baseline Neuroimaging Scan, post Neuroimaging Scan (1 week follow-up post neurostimulation)

  • Change in the ventromedial prefrontal cortex (vmPFC) for the [restructure-flow_negative] contrast

    Change in the maximum activation in the vmPFC from pre-post neuroimaging in the contrast of interest

    baseline Neuroimaging Scan, post Neuroimaging Scan (1 week follow-up post neurostimulation)

  • Change in the insular cortex for the [restructure-flow_negative] contrast

    Change in the maximum activation in the insula from pre-post neuroimaging in the contrast of interest

    baseline Neuroimaging Scan, post Neuroimaging Scan (1 week follow-up post neurostimulation)

  • Change in dorsolateral prefrontal cortex (dlPFC)-insula connectivity during [restructure - flow_negative]

    Using Generalized Psychophysiological Interaction (gPPI) analysis the difference in dlPFC-insula connectivity pre-post neuromaging

    baseline Neuroimaging Scan, post Neuroimaging Scan (1 week follow-up post neurostimulation)

  • Change in dorsolateral prefrontal cortex (dlPFC)-amygdala connectivity during [restructure - flow_negative]

    Using Generalized Psychophysiological Interaction (gPPI) analysis the difference in dlPFC-amygdala connectivity pre-post neuromaging

    baseline Neuroimaging Scan, post Neuroimaging Scan (1 week follow-up post neurostimulation)

Secondary Outcomes (10)

  • Difficulties in Emotion Regulation Scale (DERS) self-report change

    Baseline, 1 week follow-up after neurostimulation, 1 month follow-up

  • Emotion Regulation Questionnaire (ERQ) self-report change

    Baseline, 1 week follow-up after neurostimulation, 1 month follow-up

  • Change in the dlPFC for the [restructure - flow_negative] contrast

    baseline Neuroimaging scan, post Neuroimaging Scan (1 week follow-up neurostimulation)

  • Change in the amygdala for the [restructure - flow_negative] contrast

    baseline Neuroimaging scan, post Neuroimaging Scan (1 week follow-up neurostimulation)

  • Outcome Questionnaire (OQ-45) self-report change

    Baseline, 1 week follow-up after neurostimulation, 1 month follow-up

  • +5 more secondary outcomes

Other Outcomes (4)

  • Change in vmPFC-insula connectivity during [restructure - flow_negative]

    baseline Neuroimaging scan, post Neuroimaging Scan (1 week follow-up neurostimulation)

  • Cognitive flexibility inventory (CFI) and cognitive control and flexibility inventory (CCFI)

    Baseline

  • Wisconsin Card Sorting Task

    Baseline

  • +1 more other outcomes

Study Arms (3)

Cognitive Restructuring + Repetitive Transcranial Magnetic Stimulation (rTMS)

EXPERIMENTAL

Group 1 (G1)- 80 eligible participants will receive training in Cognitive Restructuring (CR). These participants will use CR while receiving rTMS over their individual dlPFC target and will partake in short term and long term follow up testing.

Device: Repetitive Transcranial Magnetic Stimulation (rTMS)Behavioral: Cognitive Restructuring

Cognitive Restructuring + scalp electrical stimulation

ACTIVE COMPARATOR

Group 2 (G2) - 80 eligible participants will receive training in CR. These participants will use CR while receiving scalp electrical stimulation over their individual dlPFC target and will partake in short term and long term follow up testing.

Device: electrical scalp stimulationBehavioral: Cognitive Restructuring

Emotional Awareness Training + Repetitive Transcranial Magnetic Stimulation (rTMS)

ACTIVE COMPARATOR

Group 3 (G3) - 80 eligible participants will receive emotional awareness training. These participants will receive rTMS over their individual dlPFC target and will partake in short term and long term follow up testing.

Device: Repetitive Transcranial Magnetic Stimulation (rTMS)Behavioral: Emotional Awareness Training

Interventions

Cognitive restructuring is a cognitive behavioral intervention through which participants learn how to think differently about stressful events in order to feel less emotional arousal.

Also known as: CR
Cognitive Restructuring + Repetitive Transcranial Magnetic Stimulation (rTMS)Cognitive Restructuring + scalp electrical stimulation

Emotional awareness training is a behavioral intervention through which participants learn how to identify and evaluate their emotions and the components that make up each emotion.

Also known as: EAT
Emotional Awareness Training + Repetitive Transcranial Magnetic Stimulation (rTMS)

high frequency rTMS over the right dlPFC

Also known as: rTMS
Cognitive Restructuring + Repetitive Transcranial Magnetic Stimulation (rTMS)Emotional Awareness Training + Repetitive Transcranial Magnetic Stimulation (rTMS)

electrical scalp stimulation over the right dlPFC

Cognitive Restructuring + scalp electrical stimulation

Eligibility Criteria

Age18 Years - 55 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • 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)
  • Naïve to rTMS

You may not qualify if:

  • 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 lesions that are contraindications for TMS, 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 (considered significant and unsafe for TMS by the study MD), 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
  • +6 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

RECRUITING

MeSH Terms

Conditions

Emotional RegulationMood DisordersStress Disorders, TraumaticAnxiety DisordersDisruptive, Impulse Control, and Conduct DisordersFeeding and Eating DisordersObsessive-Compulsive DisorderBorderline Personality Disorder

Interventions

Transcranial Magnetic StimulationCognitive Restructuring

Condition Hierarchy (Ancestors)

Self-ControlSocial BehaviorBehaviorMental DisordersTrauma and Stressor Related DisordersSigns and Symptoms, DigestiveSigns and SymptomsPathological Conditions, Signs and SymptomsPersonality Disorders

Intervention Hierarchy (Ancestors)

Magnetic Field TherapyTherapeuticsCognitive Behavioral TherapyBehavior TherapyPsychotherapyBehavioral Disciplines and Activities

Study Officials

  • Andrada D Neacsiu, PhD

    Duke University

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Lisalynn D Kelley, CCRP

CONTACT

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, OUTCOMES ASSESSOR
Masking Details
All participants will engage in a behavioral training session (either cognitive restructuring or emotional awareness training). The clinician who will conduct this behavioral session will be kept blind to thetype of neurostimulation the participant will receive. The neurostimulation technician will be kept blind to the behavioral training that the participant receives. Participants will only be told about the specific type of neurostimulation they receive at the end of the study to protect against different expectations.
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: 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).
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 12, 2023

First Posted

February 3, 2023

Study Start

May 15, 2023

Primary Completion (Estimated)

October 31, 2027

Study Completion (Estimated)

December 1, 2027

Last Updated

March 4, 2026

Record last verified: 2026-03

Data Sharing

IPD Sharing
Will share

Data from this study will be submitted to the National Institute of Mental Health Data Archive (NDA) at the National Institutes of Health (NIH). NDA is a large database where deidentified study data from many NIH studies are stored and managed. NDA is run by the National Institute of Mental Health (NIMH) that allows researchers studying mental illness and brain science to collect and share deidentified information with each other. When the study team sends the data to the NIMH, they will do this through a password secure system where participants are identified by a specific GUID which is a unique # representing 1 specific person in the nation. NIMH will also report to Congress and on its website about the different studies using NDA data. Participants can decide that they do not want to share their information to NDA.

Shared Documents
STUDY PROTOCOL, SAP, ICF
Time Frame
Either on a rolling basis over the life of the grant/project per NDA's sharing calendar. Otherwise, within 6 months of completing participant data collection or very soon after publication of primary aims.
Access Criteria
Users with NDA credentials must submit Data Access Requests for one NDA Permission Group at a time. Each DAR requires an NDA Data Use Certification (DUC) signed by the lead recipient and an authorized Signing Official from the recipient's research institution. All recipients on a Data Access Request/Data Use Certification must be affiliated with the lead recipient's research institution. If the Lead Recipient on a DUC changes institutions, they may identify another Recipient on the DUC as a replacement. Data Access Requests for a given NDA Permission Group are reviewed by one NIH-staffed Data Access Committee (DAC). Detailed information about NDA permission groups is maintained at https://nda.nih.gov/nda/about-us.html. When approved to access, teams have access to query and download all data available using the NDA Query Tool and NDA download tools.

Locations