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

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
24

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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 Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Mohana Priya Santhan Ramesh Kumar Padma, Masters
  • Phone Number: 5136364433
  • Email: priya.ramesh@cchmc.org

Study Contact Backup

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Children's Hospital Medical Center, Cincinnati

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 16, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 30, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 30, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 16, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 31, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 1, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 12, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 10, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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