Brain-Oscillation Synchronized Stimulation of the DMPFC

Official title

Brain-Oscillation Synchronized Stimulation of the DMPFC: A Single-Blind Study for Personalized Neuromodulation in OCD

Overview

This trial aims to obtain initial evidence about the clinical efficacy and modulation of neurophysiological markers in obsessive compulsive disorder (OCD) using personalized (i.e., electroencephalography (EEG)-triggered) repetitive transcranial magnetic stimulation (rTMS) as compared to non-personalized (i.e., non-EEG triggered), standard rTMS applied to the dorsomedial prefrontal cortex.

Detailed description

This trial uses a prospective, randomized, single-blind study design with two treatment arms at the Centre for Addiction and Mental Health (CAMH) in Toronto, ON. The study aims to compare the clinical effects of EEG-triggered, personalized rTMS (i.e., experimental arm) in the treatment of OCD to those of non-EEG triggered, non-personalized rTMS (i.e., active-comparator arm). Additionally, the study aims to compare the modulation of neurophysiological (i.e., EEG) markers of OCD between the two arms.

Study treatment will be administered five days per week across a six-week treatment course for a total of 30 sessions. Both rTMS arms will use the same TMS coil, stimulation intensity, number of pulses, and anatomical target (i.e., dorsomedial prefrontal cortex).

Clinical outcomes will be measured using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) with clinical response defined as a ≥30% improvement on the Y-BOCS. The self-reported revised Obsessive Compulsive Inventory (OCI-R) and Clinical Global Impressions - Improvement (CGI-I) scale will also be used. Neurophysiological outcomes will be measured by the change in frontoparietal theta amplitude (i.e., 4-7 Hz) and power of TMS-induced theta oscillations.

Interventions

• Device EEG-Triggered Repetitive Transcranial Magnetic Stimulation (rTMS)
  The rTMS intervention will be delivered using the MagPro XP - Orange Edition stimulator and COOL D-B80 coil to the dorsomedial prefrontal cortex 4 cm anterior to the foot hotspot. EEG data will be analyzed in real-time using the bossdevice MEDICAL and TMS pulses will be synchronized to the negative peak of the frontoparietal theta oscillation. 500 consecutive EEG theta-oscillation negative-peak triggered quadruplet bursts with a 5 ms inter-pulse interval will be applied at an average inter-burs
• Device Non-EEG Triggered Repetitive Transcranial Magnetic Stimulation (rTMS)
  The rTMS intervention will be delivered using the MagPro XP - Orange Edition stimulator and COOL D-B80 coil to the dorsomedial prefrontal cortex 4 cm anterior to the foot hotspot. High-frequency rTMS consisting of 50 trains at 20 Hz (2 s on, 18 s off) will be delivered. The therapeutic intervention consists of 30 sessions of 2000 TMS pulses each for a total duration per treatment session of 17 minutes.

Primary outcome measures

• Yale-Brown Obsessive Compulsive Scale (Y-BOCS) [Time frame: From screening to the end of the follow-up period (1 week post-intervention)]

Secondary outcome measures (3)

• Obsessive Compulsive Inventory - Revised (OCI-R) [Time frame: From screening to the end of the follow-up period (1 week post-intervention)]
• Clinical Global Impressions - Improvement (CGI-I) Scale [Time frame: From screening to the end of the follow-up period (1 week post-intervention)]
• Electroencephalography (EEG) Markers of OCD [Time frame: From screening to the end of the follow-up period (1 week post-intervention)]

Eligibility criteria

Inclusion criteria

• Are 18-65 years old;
• Have OCD as a primary disorder, confirmed by a Mini-International Neuropsychiatric Interview (MINI) diagnosis of OCD, with treatment resistance defined as a failure of at least one course of cognitive-behavioural therapy or a single trial of an SSRI;
• Does not meet criteria for substance use disorder as determined by the MINI (with the exception of nicotine and caffeine);
• Have a Y-BOCS score >20;
• Are fluent in the English language (spoken, written, reading);
• Have had no increase or initiation of any psychotropic medication in the 4 weeks prior to screening;
• Must be deemed to have capacity to provide informed consent;
• Must sign and date the informed consent form;
• Stated willingness to comply with all study procedures.

Exclusion criteria

• Have any contraindications to TMS as determined by the Transcranial Magnetic Stimulation Adult Safety Screen (TASS) questionnaire;
• Have a history of a medical or neurological disorder that affects the central nervous system (e.g., traumatic brain injury, stroke, Parkinson's disease);
• Are pregnant or breast feeding. TMS is not unsafe in pregnancy and therefore the study team is not requiring a pregnancy test prior to entry. If participants become pregnant during the study they will not be excluded. The study team is not including people who are currently aware of being pregnant as OCD can be affected during the later stages of pregnancy and therefore is a potential confound;
• Have a history of seizures;
• Have any metal implants or dentures;
• Have a serious or unstable medical condition requiring immediate investigation or treatment (e.g., severe or recent cardiac disease);
• Have a cardiac pacemaker, cochlear implants, implanted electronic devices, non-electronic metallic implants, or other contraindications for rTMS;
• Take more than 2mg of lorazepam or equivalent benzodiazepine, or any anticonvulsant medication;
• Fulfill criteria for Alcohol Use Disorder.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

Canada · 1 center

• Centre for Addiction and Mental Health — Toronto

Identifiers

NCT: NCT06942559 · 104-2023

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗