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Transcranial Direct Current Stimulation and Fear Extinction

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ClinicalTrials.gov Identifier: NCT03907917
Recruitment Status : Recruiting
First Posted : April 9, 2019
Last Update Posted : July 12, 2019
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Yale University

Brief Summary:

Psychiatric disorders characterized by pathological fear and anxiety are common and often disabling. Despite their limitations, exposure therapies are among the most efficacious treatments for these disorders. Extinction learning is thought to be a core mechanism of therapeutic exposure. Extinction learning is mediated by a well-defined circuit encompassing the medial prefrontal cortex (mPFC), amygdala, and hippocampus. This raises the exciting possibility that direct engagement of this circuitry might enhance the response to therapeutic exposure. Transcranial direct current stimulation (tDCS) is a neuromodulation technology that can augment brain plasticity, learning, and memory. The proposed study will evaluate whether tDCS can engage extinction circuitry, and improve extinction learning and memory.

This study will enroll psychiatrically healthy volunteers to test whether tDCS applied to the mPFC can augment spontaneous mPFC activity, engagement of extinction circuitry during extinction learning and recall, and classically-conditioned extinction learning and memory. Healthy volunteers will complete a standardized, three-day fear conditioning and extinction learning and memory task. On day 1, participants will complete a fear conditioning task. On day 2, participants will receive sham (placebo) or active tDCS prior to completing a fear extinction learning task. On day 3, participants will complete an extinction recall task. Electrodermal activity and heart rate will be continuously monitored during the conditioning and extinction procedures to assess autonomic arousal. All procedures will be completed in a magnetic resonance imaging (MRI) scanner; imaging data will be collected before and after tDCS and during all conditioning and extinction procedures.


Condition or disease Intervention/treatment Phase
Anxiety Disorders Device: tDCS Not Applicable

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 64 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Subjects will be randomly assigned to receive Active (real) or Sham (placebo) transcranial direct current stimulation.
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description: Randomization will be administrated by independent research staff. Double-blind software will be used to ensure that the experimenter and subject remain blind during task administration.
Primary Purpose: Basic Science
Official Title: The Effects of Transcranial Direct Current Stimulation on Fear Extinction Learning and Memory Processes
Actual Study Start Date : April 9, 2019
Estimated Primary Completion Date : April 30, 2022
Estimated Study Completion Date : December 31, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Anxiety

Arm Intervention/treatment
Active Comparator: Active tDCS
Current will be ramped in/out for 30 seconds at the begging and end of a 20-minute period and a constant current will be delivered for the 20-minutes between ramping.
Device: tDCS
Subjects will receive 20 minutes of multifocal transcranial direct current stimulation. The anode will be placed over the frontal pole (Fpz, 10-20 EEG) and will be surrounded by 5 return electrodes (cathodes). Current will be set at 1.5mA and will be ramped in/out at the begging and end of the 20-minutes of stimulation over the course of 30 seconds.
Other Names:
  • transcranial direct current stimulation
  • transcranial electrical stimulation
  • Starstim®

Sham Comparator: Sham tDCS
Current will be ramped in/out for 30 seconds at the begging and end of a 20-minute period during which no stimulation will be delivered.
Device: tDCS
Subjects will receive 20 minutes of multifocal transcranial direct current stimulation. The anode will be placed over the frontal pole (Fpz, 10-20 EEG) and will be surrounded by 5 return electrodes (cathodes). Current will be set at 1.5mA and will be ramped in/out at the begging and end of the 20-minutes of stimulation over the course of 30 seconds.
Other Names:
  • transcranial direct current stimulation
  • transcranial electrical stimulation
  • Starstim®




Primary Outcome Measures :
  1. Fractional amplitude of low frequency fluctuations (fALFF) [ Time Frame: Immediately following administration of tDCS on day 2 of the protocol. ]
    fALFF is a measure of resting brain activity that is derived by calculating regionally-specific fluctuations in Blood Oxygen Level-Dependent (BOLD) activation within a low-frequency band, typically while the participant is at rest.

  2. Event related brain activation during extinction learning [ Time Frame: BOLD imaging will be measured during extinction training on day 2 of the protocol. ]
    Blood Oxygen Level-Dependent imaging (BOLD imaging) will be measured during extinction training.

  3. Event related brain activation during extinction recall [ Time Frame: BOLD imaging will be measured during the test of extinction recall on day 3 of the experimental protocol. ]
    Blood Oxygen Level-Dependent imaging (BOLD imaging) will be measured during extinction recall.

  4. Skin conductance response (SCR) during extinction learning [ Time Frame: SCR will be measured during extinction learning on day 2 of the experimental protocol. ]
    SCR will be measured by collecting electrodermal activity (EDA) on the left hand and subtracting the maximal EDA value during the presentation of the virtual context (CX) picture from the maximal EDA value during the presentation of the conditioning stimuli (CS).

  5. Skin conductance response (SCR) during extinction recall [ Time Frame: SCR will be measured during extinction recall on day 3 of the experimental protocol. ]
    SCR will be measured by collecting electrodermal activity (EDA) on the left hand and subtracting the maximal EDA value during the presentation of the virtual context (CX) picture from the maximal EDA value during the presentation of the conditioning stimuli (CS).


Secondary Outcome Measures :
  1. Functional connectivity measure of tDCS [ Time Frame: Immediately prior to and following administration of tDCS. Change in connectivity from pre to post stimulation (delta) will be modeled and used as the dependent variable. ]
    Correlations between brain regions over the time course.

  2. Functional connectivity during extinction learning [ Time Frame: During extinction learning on day 2 of the experimental protocol. ]
    Correlations between brain regions over the time course

  3. Functional connectivity during extinction recall [ Time Frame: During extinction recall on day 3 of the experimental protocol. ]
    Correlations between brain regions over the time course



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Ability to provide informed consent (as established by clinical interview), and voluntary, signed informed consent prior to the performance of any study-specific procedures;
  • Ability and willingness to perform study-relevant clinical assessments;
  • Ability and willingness to receive transcranial direct current stimulation (tDCS);
  • Ability and willingness to complete magnetic resonance imaging (MRI) scans;
  • Free of current psychiatric diagnosis;
  • Psychiatrically healthy;
  • 18-55 years of age;
  • Medication free or stable (> 4 weeks) medication(s).

Exclusion Criteria:

  • Any unstable medical, psychiatric, or neurological condition (including active or otherwise problematic suicidality) that may necessitate urgent treatment;
  • Any substance dependence or severe substance abuse within the past 6 months;
  • Daily use of psychotropic medications that substantially lower seizure threshold (e.g., clozapine);
  • Daily use of psychotropic drugs that may interfere with extinction learning (e.g., anxiolytics);
  • Any history of a psychotic disorder or of mania;
  • Current active suicidal ideation or any suicidal intent;
  • Any major neurological disease or history of major head trauma, including concussion with extended loss of consciousness, or of psychosurgery;
  • Any history of epilepsy;
  • Pregnancy;
  • Any metal in the body or other contraindication to MRI scanning or tDCS;
  • Any history of adverse effects to brain stimulation;
  • A current Diagnostic and Statistical Manual diagnosis in the past 6 months, as determined by clinical interview;
  • History of a severe psychiatric disorder, either documented or by clinician judgment;
  • Use of drugs that are known to influence hemodynamic properties, except for drugs that are used to treat hypertension;
  • Severe claustrophobia, back pain, or other condition that may make an extended magnetic resonance scan difficult or lead to excessive movement during the scan.

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): NCT03907917


Contacts
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Contact: Eileen Billingslea, MA 203-974-7768 eileen.billingslea@yale.edu
Contact: Thomas Adams, PhD 203-974-7496 thomas.adamsjr@yale.edu

Locations
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United States, Connecticut
Connecticut Mental Health Center Recruiting
New Haven, Connecticut, United States, 06511
Contact: Eileen Billingslea, MA    203-974-7768    eileen.billingslea@yale.edu   
Sponsors and Collaborators
Yale University
National Institute of Mental Health (NIMH)

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Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT03907917     History of Changes
Other Study ID Numbers: Adams_K23
1K23MH111977 ( U.S. NIH Grant/Contract )
First Posted: April 9, 2019    Key Record Dates
Last Update Posted: July 12, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Raw imaging and psychophysiological data will be freely available upon study publication. Data will be stored on a yet to be determined data sharing repository supported by the National Institutes of Health.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Analytic Code
Time Frame: Data will be made available following study publication.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Anxiety Disorders
Mental Disorders