Obsessive-Compulsive Disorder
Conditions
Keywords
Obsessive-Compulsive Disorder, OCD, Fear extinction, tDCS, transcranial Direct Current Stimulation, Randomized controlled trial, Fear conditioning
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.
Interventions
DEVICEActive tDCS
The investigators will use commercially available tDCS equipment (Neuroelectrics©, Barcelona, Spain). The cathode will be placed over the pre-SMA using the 10-20 EEG system and the anode will be on the right deltoid.
DEVICESham tDCS
The investigators will use commercially available tDCS equipment (Neuroelectrics©, Barcelona, Spain). The cathode will be placed over the pre-SMA using the 10-20 EEG system and the anode will be on the right deltoid. tDCS will not be active in this condition.
Sponsors
Massachusetts General Hospital
Foundation for OCD Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 in the difference in frontomedial theta event-related spectral perturbation (ERSP) between CS+ vs CS- indicates more complete neural extinction of the conditioned fear response, reflecting diminished differential threat processing such that the previously conditioned stimulus is being processed more similarly to the safe stimulus. |
| Difference in the Square Root Skin Conductance Response (SCR) to the Conditioned Stimulus (CS+) Versus the Unconditioned Stimulus (CS-) Between tDCS Conditions During the First 12 Trials of Extinction Recall | Extinction Recall Phase (Day 2) | Higher skin conductance (microSiemens) indicates greater fear intensity. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORJoan Camprodon, MD, MPH, PhD
Massachusetts General Hospital
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 27.1 years STANDARD_DEVIATION 8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 0 Participants |
| Race/Ethnicity, Customized Race Another race | 2 Participants |
| Race/Ethnicity, Customized Race Asian | 11 Participants |
| Race/Ethnicity, Customized Race Black/African American | 3 Participants |
| Race/Ethnicity, Customized Race More than one race | 1 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Pacific Islander | 0 Participants |
| Race/Ethnicity, Customized Race Unknown/not reported | 0 Participants |
| Race/Ethnicity, Customized Race White | 16 Participants |
| Region of Enrollment United States | 22 Participants |
| Sex/Gender, Customized Sex Female | 18 Participants |
| Sex/Gender, Customized Sex Male | 20 Participants |
| Sex/Gender, Customized Sex Prefer not to answer | 1 Participants |
| Y-BOCS | 21.0 Scores on a scale STANDARD_DEVIATION 4.3 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 22 | 0 / 21 | 0 / 22 |
| other Total, other adverse events | 21 / 21 | 21 / 22 | 21 / 21 | 21 / 22 |
| serious Total, serious adverse events | 0 / 21 | 0 / 22 | 0 / 21 | 0 / 22 |
Outcome results
None listed