Evaluate the efficacy of accelerated theta burst stimulation (aTBS) in reducing depressive symptoms in autism spectrum disorder (ASD)
The overall goal of this study is to treat major depressive disorder (MDD) rapidly and effectively in individuals with autism spectrum disorder (ASD). Our central hypothesis is that accelerated theta burst stimulation (aTBS) targeting the left dorsal lateral prefrontal cortex (DLPFC) will significantly improve MDD symptoms and rate of remission compared to sham. We propose a double-blind RCT of 13-to 26-year-old individuals with ASD with MDD to test the efficacy of aTBS (n=12) versus sham (n=12) treatment. Participants will be rigorously characterized, including co-occurring conditions, any concurrent therapies, medications, social function, cognition, and sensory profile. A core battery of assessments will assess the efficacy of the intervention and maintenance of gains with respect to MDD and ASD-specific symptomology. Neural target engagement will be assessed by source-localized Electroencephalography (EEG) connectivity.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
24
All TBS sessions will be delivered at the same site, intensity (up to 90% RMT), pattern and duration. Treatment conditions differ only in the amount of intracranial activation induced (i.e., negligible activation in sham condition). TBS sessions consist of triplet 50 Hz bursts repeated every 200 msec (5 Hz), delivered to the left DLPFC in an intermittent (2 seconds on/8 seconds off) pattern for a total of 600 pulses per session; duration of 3 minutes 9 seconds.
We will use a robust sham technique that suitably replicates the sensory experience (auditory and peripheral activation) of active TBS with minimal intracranial activation. The Magstim Horizon™ sham coil will be utilized for treatment delivery. This sham coil is visually identical to the active coil and replicates the sounds and sensation of the magnetic stimulation. All sham treatment will be delivered at the same site, intensity (up to 90% RMT), pattern and duration. Treatment conditions differ only in the amount of intracranial activation induced (i.e., negligible activation in sham condition). TBS sessions consist of triplet 50 Hz bursts repeated every 200 msec (5 Hz), delivered to the left DLPFC in an intermittent (2 seconds on/8 seconds off) pattern for a total of 600 pulses per session; duration of 3 minutes 9 seconds
Cincinnati Childrens Hospital Medical Center
Cincinnati, Ohio, United States
17-item Hamilton Rating Scale for Depression (HDRS)
The HDRS is a 17-item rating scale administered by a trained rater following a semi-structured interview. Scores of 0-7 are generally within the normal range, and a score of 20 or higher indicates moderate depression severity. Research suggests that a decrement of 7 points on the HAMD-17 represents minimally clinically important differences from patient perspectives. HDRS will be assessed at screening, baseline and all follow up visits.
Time frame: Completed at Screening, baseline, 2-week, 6-week, and 12-week follow up
NIH Toolbox Cognition Battery
The NIH Toolbox was designed to serve as a brief, convenient set of measures to supplement other outcome measures in epidemiologic and longitudinal research and clinical trials.
Time frame: Completed at Screening, 2-week, 6-week, and 12-week follow up
Electroencephalography (EEG)
Recordings are acquired using a gel-based electrode setup with a Biosemi EEG system, featuring 64 channels. Data are recorded at a sampling rate of 256 Hz, utilizing gel-based electrodes that enhance conductivity and minimize noise. This configuration ensures high-quality signal acquisition, enabling precise analysis of brain responses to various stimuli. EEG offers a real-time image of cortical excitability and connectivity. We will use power spectral analysis to assess changes in event-related gamma and alpha activity.
Time frame: Completed at baseline, 2-week, 6-week, and 12-week follow up
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