Theta Burst Stimulation for Refractory Depression in Autism Spectrum Disorder

Not Applicable

Recruiting

• Conditions: ASD; Autism Spectrum Disorder; Autism; Depression - Major Depressive Disorder; MDD

• Registration Number: NCT06670040
• Lead Sponsor: Children's Hospital Medical Center, Cincinnati

Brief Summary

Evaluate the efficacy of accelerated theta burst stimulation (aTBS) in reducing depressive symptoms in autism spectrum disorder (ASD)

Detailed Description

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 Timeline

• Study Start: 2024-09-16
• Status Verified: 2024-10
• Study First Submitted: 2024-10-16
• Study First Submitted QC: 2024-10-31
• Last Update Submitted: 2024-10-31
• Study First Posted: 2024-11-01
• Last Update Posted: 2024-11-01
• Primary Completion: 2026-01-31
• Study Completion: 2026-01-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

1. Fluent in English and able to volunteer in the informed consent process and provide spontaneous narrative description of key elements, risks, and benefits of the study.
2. Aged 13-26, inclusive.
3. Full-scale intelligence quotient ≥ 70.
4. Diagnosis of ASD using criteria from Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5). Diagnosis will be confirmed by study psychologist/social worker and supported by scoring in the ASD on the Autism Diagnostic Observation Schedule (ADOS-2).
5. Diagnosis of MDD based on psychologist diagnosis and DSM-5-based structural diagnostic interview determine via KSADS
6. Exhibiting treatment resistance to at least one antidepressant drug treatment of adequate dose and duration.
7. Symptoms of moderate to severe depression according to Hamilton Depression Rating Scale ≥ 20 which must be maintained through lead-in period.
8. Participants are not required to discontinue current interventions but must agree to attempt to keep medications and other interventions stable during the study.

Exclusion Criteria

1. Participation in an investigational drug trial within the past three months.
2. Active substance use disorder (excluding tobacco use) within the past 6 months.
3. Contraindications to Transcranial Magnetic Stimulation including, but not limited to, a history of epilepsy, the presence of metallic foreign bodies, or implanted medical devices (e.g. pacemaker, medical pump).
4. Actively suicidal (i.e., suicidal ideation with plan and intent) or deemed at high risk for suicide.
5. Current use of anticonvulsant, barbiturate, lithium, or benzodiazepine medications.
6. Prior rTMS treatment.
7. For female subjects of childbearing potential, a positive urine pregnancy test.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
17-item Hamilton Rating Scale for Depression (HDRS)	Completed at Screening, baseline, 2-week, 6-week, and 12-week follow up	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.
NIH Toolbox Cognition Battery	Completed at Screening, 2-week, 6-week, and 12-week follow up	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.

Secondary Outcome Measures

Name	Time	Method
Electroencephalography (EEG)	Completed at baseline, 2-week, 6-week, and 12-week follow up	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.

Trial Locations

Locations (1)

Cincinnati Childrens Hospital Medical Center; 🇺🇸 Cincinnati, Ohio, United States