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

February 10, 2026 updated by: Rana Elmaghraby, Children's Hospital Medical Center, Cincinnati

Sham-Controlled rTMS for Refractory Depression in Autism Spectrum Disorder

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

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

24

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Ohio
      • Cincinnati, Ohio, United States, 45224
        • Cincinnati Childrens Hospital Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Sham Comparator: Sham controlled
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.
Procedure: Transcranial Magnetic Stimulation Sham
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
Active Comparator: Active TBS Treatment
Active aTBS targeting the left dorsolateral prefrontal cortex, 5 sessions per day for 5 days.
Procedure: Transcranial Magnetic Stimulation
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.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Electroencephalography (EEG)
Time Frame: 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.
Completed at baseline, 2-week, 6-week, and 12-week follow up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Children's Hospital Medical Center, Cincinnati

Investigators

  • Principal Investigator: Rana Elmaghraby, MD, Cincinnati Childrens Hospital Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 16, 2024

Primary Completion (Estimated)

April 30, 2026

Study Completion (Estimated)

April 30, 2026

Study Registration Dates

First Submitted

October 16, 2024

First Submitted That Met QC Criteria

October 31, 2024

First Posted (Actual)

November 1, 2024

Study Record Updates

Last Update Posted (Actual)

February 12, 2026

Last Update Submitted That Met QC Criteria

February 10, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2023-0682

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

All the IPD collected throughout this trial

IPD Sharing Time Frame

After the completion of data collection

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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