Transcranial Direct Current Stimulation Potentiation of Fear Extinction in OCD

Not Applicable

Recruiting

• Conditions: Obsessive-Compulsive Disorder
• Interventions: Device: Active tDCS; Device: Sham tDCS

• Registration Number: NCT05521074
• Lead Sponsor: Massachusetts General Hospital

Brief Summary

The investigators want to learn more about how human beings learn not to fear and the impact of changing the fear network in the brain using transcranial Direct Current Stimulation (tDCS) in individuals with obsessive compulsive disorder (OCD). The investigators hope this study will help us understand how future treatments can help patients with OCD better control unwanted fear.

Detailed Description

To address this question behaviorally and biologically, the investigators will use a, 2-day fear extinction paradigm while measuring behavioral psychophysiology (skin conductance response \[SCR\]) and neurophysiology (electroencephalography \[EEG\]). On Day 1 participants will undergo 1) habituation, 2) fear conditioning, and 3) extinction learning. On Day 2 they will undergo 4) extinction recall, and 5) reinstatement. SCR and EEG will be measured in both sessions. The investigators propose to investigate whether inhibitory tDCS to the pre-SMA before, during, or after fear extinction significantly 1) enhances the recall of extinction learning and 2) reduces fronto-medial theta power during extinction recall. Participants will be randomized to one of the following four conditions: active tDCS before, during, or after extinction learning, or sham tDCS. The fear extinction paradigm serves as a proxy of exposure-based CBT for OCD. Defining the combination protocol that optimally and significantly increases extinction recall behaviorally (psychophysiology) in OCD, will have critical implications for the mechanistically informed development of tDCS-augmented CBT for OCD. EEG measures will provide a response biomarker to characterize target engagement neurophysiologically. This is particularly relevant given EEG's ease of use, relatively low cost, and potential for greater translation to the clinic. Also, the higher signal-to-noise ratio (SNR) of EEG compared to SCR is a strength. Taken together, these data should reveal treatment targets, define optimal therapeutic protocols, and provide the foundation for a future clinical trial to test the synergistic efficacy of combined tDCS-CBT for OCD.

Study Timeline

• Study First Submitted: 2022-08-26
• Study First Submitted QC: 2022-08-26
• Study First Posted: 2022-08-30
• Study Start: 2022-09-15
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-27
• Last Update Posted: 2024-07-30
• Primary Completion: 2025-03
• Study Completion: 2025-03

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

• Fluent in English, willing to provide informed consent, and willing to comply with the study protocol
• Primary OCD that causes at least moderate distress and/or impairment (Y-BOCS total score ≥ 16)
• Comfortable and capable of using a computer and completing computerized tasks

Exclusion Criteria

• History of head injury resulting in prolonged (i.e., >1h) loss of consciousness and/or neurological sequelae; history of stroke; signs of increased intracranial pressure; prior neurosurgical procedure (e.g., DBS, aneurysm clips)
• Contraindications to participate in tDCS including: metallic implants in head or neck; ventriculoperitoneal (VP) shunts; pacemakers; pregnancy; epilepsy.
• Current or history of neurologic or psychiatric disease (e.g., mental retardation, dementia, brain damage, or other cognitive impairment) that would interfere with ability to participate in the study
• Impaired (or uncorrected) vision that would interfere with participation.
• Current clinically significant suicidality that requires psychiatric hospitalization, as indicated by clinical judgment.
• Current substance use disorder (within the past 12 months)
• Lifetime manic episode or psychosis
• Documented resistance to 4 or more valid pharmacological trials and previous treatment with ≥12 sessions of cognitive behavioral therapy for OCD with no response (or worsening symptoms)
• Use of most psychotropic medications (e.g., SSRIs and atypical antipsychotics) will be allowed. However, use of benzodiazepines within 2 weeks prior to the study is exclusionary (and participants will be asked to refrain from use of such medications during the study as they may interfere with the fear extinction paradigm).
• Unable to obtain low enough impedance values to ensure safe and effective application of tDCS/EEG.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Active tDCS administered after extinction phase	Active tDCS	The investigators will stimulate using 2mA of direct current during 20 min after the extinction phase of the fear conditioning and extinction paradigm.
Active tDCS administered before extinction phase	Active tDCS	The investigators will stimulate using 2mA of direct current during 20 min before the extinction phase of the fear conditioning and extinction paradigm.
Active tDCS administered during extinction phase	Active tDCS	The investigators will stimulate using 2mA of direct current during 20 min during the extinction phase of the fear conditioning and extinction paradigm.
Sham tDCS	Sham tDCS	Sham will consist of a ramp up and down of activity (from 0 to 2mA and back to 0mA) in the first 30sec and again in the last 30 sec of the 20min stimulation period (which will occur before/during/after the extinction phase). No active tDCS will occur.

Primary Outcome Measures

Name	Time	Method
Difference in frontomedial theta power (EEG) to the conditioned stimulus (CS+) versus the unconditioned stimulus (CS-) between tDCS conditions during extinction recall	Extinction Recall Phase (Day 2)	Greater reduction of frontomedial theta power (microvolts) indicates stronger extinction recall.
Difference in skin conductance response (SCR) to the conditioned stimulus (CS+) versus the unconditioned stimulus (CS-) between tDCS conditions during extinction recall	Extinction Recall Phase (Day 2)	Higher skin conductance (microSiemens) indicates greater fear intensity.

Trial Locations

Locations (1)

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States