Clinical trial NCT05521074: Transcranial Direct Current Stimulation Potentiation of Fear Extinction in OCD
Official title: Transcranial Direct Current Stimulation Potentiation of Fear Extinction in OCD: Towards Rational Design of Combination Therapies
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Obsessive-Compulsive Disorder
Keywords: Obsessive-Compulsive Disorder
OCD
Fear extinction
tDCS
transcranial Direct Current Stimulation
Randomized controlled trial
Fear conditioning
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: Foundation for OCD Research
First posted: 2022-08-30
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Difference in skin conductance response (SCR) to the conditioned stimulus (CS+) versus the unconditioned stimulus (CS-) between tDCS conditions during extinction recall
timeFrame: Extinction Recall Phase (Day 2)
measure: Difference in frontomedial theta power (EEG) to the conditioned stimulus (CS+) versus the unconditioned stimulus (CS-) between tDCS conditions during extinction recall
timeFrame: Extinction Recall Phase (Day 2)
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Joan Camprodon, MD, MPH, PhD
role: PRINCIPAL_INVESTIGATOR
References: