Theta Burst Stimulation for Refractory Depression in Autism Spectrum Disorder (RETSORE-RCT)

Cincinnati Children's Hospital Medical Center

Status: Enrolling

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

Treatments: Procedure: Transcranial Magnetic Stimulation; Procedure: Transcranial Magnetic Stimulation Sham

Study type: Interventional

Funder types: Other

Identifiers

NCT06670040

2023-0682

Details and patient eligibility

About

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

Full 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.

Enrollment: 24 estimated patients

Sex: All

Ages: 13 to 26 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

---

24 participants in 2 patient groups

Sham controlled

Sham Comparator group

Description:

Sham aTBS targeting the left dorsolateral prefrontal cortex, 5 sessions per day for 5 days. If participants in the sham group do not show a significant treatment response by the 12-week follow-up - defined as a 50% reduction from baseline on the HDRS- they will then become eligible for and offered active, open-label treatment.

Treatment:

Procedure: Transcranial Magnetic Stimulation Sham

Active TBS Treatment

Active Comparator group

Description:

Active aTBS targeting the left dorsolateral prefrontal cortex, 5 sessions per day for 5 days.

Treatment:

Procedure: Transcranial Magnetic Stimulation