Autism Spectrum DisorderrTMS-MDDNCT04972136
rTMS for Depression in Young Adults With Autism
A study testing Active Bilateral Theta Burst Stimulation in people with Autism Spectrum Disorder and Major Depressive Disorder, run by Centre for Addiction and Mental Health at 1 site in Canada.
Trial summary
The current clinical trial is focused on evaluating the efficacy of rTMS for treatment of depression in youth and young adults (hereafter called transition aged youth, TAY) with autism spectrum disorder (ASD). Read more about this study
- Who is it for?
- Ages 16 to 35 years
- Conditions the study is for
- Autism Spectrum Disorder, Major Depressive Disorder
- What is being tested?
- Active Bilateral Theta Burst Stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteCanada
- Study dates
- 14 Jan 2021to 14 Jan 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 35 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Fluent in English
- ASD diagnosis confirmed by the clinician/clinical team, and IQ> or =70
- Able to participate in the informed consent process, provide voluntary informed consent and provide a spontaneous narrative description of the key elements of the study
- Clinical stability: determined by a physician, no switch of psychotropic medications or increase in dosage in the last 30 days; no change in other therapeutic interventions in last 30 days
- BDI-II score ≥21 that is sustained over a lead-in period of two weeks
- Global Assessment of Function (GAF) scores (≤60) that is sustained over a lead-in period of two weeks AND/OR VABS-III below adequate functioning at baseline assessment.
Who cannot join
- A history of a DSM-5 substance use disorder (other than tobacco) within the past six months; or a positive baseline urine drug screen
- Significantly debilitating medical or neurologic illness, or acute or unstable medical illnesses as determined by study physician
- Metal implants or a pace-maker, claustrophobia that would preclude the MRI scan
- Actively suicidal (i.e., suicidal ideation with plan and intent) or high risk for suicide as assessed by a study psychiatrist
- History of seizures
- Taking benzodiazepines at a dose greater or equal to 2mg Lorazepam or any anticonvulsant medication
- Prior rTMS treatment
- Pregnancy
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site, 1 recruiting
- Recruiting
Centre for Addiction and Mental Health
Toronto, Ontario, M6J 1H4
About this study
Official title: A Double-Blind Randomized Controlled Trial Evaluating the Efficacy of Repetitive Transcranial Magnetic Stimulation (rTMS) as Treatment for Major Depressive Disorder in Transition-Age Youth With Autism Spectrum Disorder
The current clinical trial is focused on evaluating the efficacy of rTMS for treatment of depression in youth and young adults (hereafter called transition aged youth, TAY) with autism spectrum disorder (ASD). The motivation to undertake the current efficacy study is driven by: (1) the substantial impact of depression on TAY with ASD (based on prevalence and contribution to disability/impairment); (2) lack of evidence-based treatments for depression in autism (there are no current trials rigorously evaluating any treatment for depression, i.e., psychotherapeutic, pharmacotherapeutic, brain stimulation); (3) rTMS has demonstrated efficacy in non-autistic individuals to improve symptoms of depression and may be better tolerated in youth than medication treatment; (4) a prior pilot rTMS study focused on treatment of executive function deficits in autism indicated that high frequency rTMS delivered using a rigorous randomized control trial (RCT) protocol can be feasibly implemented in TAY with autism, is well tolerated (mild to moderate adverse effects and low drop out), and has the potential to improve symptoms of depression.
Read the detailed description
The investigators will use a randomized, double-blind, sham-controlled design of bilateral theta burst stimulation (BL-TBS) to dorsolateral prefrontal cortex (DLPFC) administered 5 days per week for 6 weeks (30 sessions). The investigators will recruit n=80, 16-35 year old participants with autism that do not have co-occurring intellectual disability (ID). In the current study, the target population will be individuals with autism, without ID who have co-occurring clinically significant depression. Pre/post treatment MRI will be used to study mechanisms of treatment response. The investigators will build on their previous pilot rTMS study in autism with two key innovations. First, the investigators will use theta burst stimulation (TBS) for depression as opposed to conventional rTMS. TBS is a newer form of rTMS shown to be non-inferior to conventional rTMS for depression with a similar safety profile. Tolerance of intermittent TBS (iTBS, delivered at 100% RMT to right DLPFC in ten 9-17 year-olds with ASD) has already been shown in autism in a prior open-label study. Importantly, TBS can be delivered in a fraction of the time needed for conventional rTMS. This shorter administration time may be critical for participant retention as sensory sensitivity is a major feature of autism. A shorter administration also has important practical implications for future clinical access. The investigators will use BL-TBS based on: preliminary data of improved antidepressant efficacy with a bilateral (over unilateral) TBS approach that combines left excitatory with right inhibitory DLPFC stimulation, as well as findings that bilateral (over unilateral) rTMS may improve suicidal ideation in MDD.
- Being tested
- Active Bilateral Theta Burst Stimulation, Sham Bilateral Theta Burst Stimulation
- Keywords
- Autism Spectrum Disorder, Major Depressive Disorder, rTMS (Repetitive Transcranial Magnetic Stimulation), MRI (Magnetic Resonance Imaging), Suicidal and Self-Injurious Behaviour, Adaptive Functioning
- Medical subject headings
- Autism Spectrum Disorder, Depressive Disorder, Major, Self-Injurious Behavior
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active Bilateral Theta Burst StimulationDevice
Also called X100 with a B65-type coil (Magventure Inc.)
A total of 30 active BL-TBS sessions. Stimulation will begin with right DLPFC (cTBS) followed by left DLPFC (iTBS)
Sham Bilateral Theta Burst StimulationDevice
Also called X100 with a B65-type coil (Magventure Inc.)
A total of 30 sham BL-TBS sessions. Stimulation will begin with right DLPFC (cTBS) followed by left DLPFC (iTBS)
| Study group | Role | What they receive |
|---|---|---|
| Active bilateral theta burst stimulation | Active comparator | An X100 stimulator with a B65 A/P type coil (Magventure Inc.) will be used. The coil is positioned under MRI guidance using real-time neuronavigation using Brainsight [x,y,z= -38, 44, 26(left), +38, 44, 26 (right). BL-TBS will be delivered at 90% RMT, corrected for scalp to cortex distance, to targeted left and right DLPFC sites, differing only in stimulation pattern and total number of pulses (triplet 50 Hz bursts, repeated at 200 msec (i.e., 5 Hz); right DLPFC (continuous TBS, cTBS): 120 seconds uninterrupted bursts (total of 600 pulses); left DLPFC (intermittent TBS, iTBS: 2 seconds on and 8 seconds off; 600 pulses per session; total duration of 3 min 9 seconds/hemisphere). Receives: Device: Active Bilateral Theta Burst Stimulation |
| Sham bilateral theta burst stimulation | Sham comparator | An X100 stimulator with a B65 A/P type coil (Magventure Inc.) will be used with the active coil facing away from the scalp, for sham stimulation. The coil is positioned under MRI guidance using real-time neuronavigation using Brainsight [x,y,z= -38, 44, 26(left), +38, 44, 26 (right). To reproduce the nociceptive qualities of the stimulation, the B65-type stimulation coil - sham side - includes a built in electrical stimulator in the coil connector which "fires" a synchronous electrical pulse along with the TMS stimulus through electrodes mounted on the forehead or near the area of stimulation, to generate auditory and somatosensory (vibration) stimuli. Receives: Device: Sham Bilateral Theta Burst Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in scores on the 17-item Hamilton Rating Scale for Depression (HRSD-17)
The investigators will evaluate the changes in the severity of symptoms of depression before, during, and after rTMS treatment. HRSD-17 scores range from 0 to 52, with higher scores indicating greater severity of depressive symptoms (worse outcome).
Measured: Baseline, end of weeks 1, 2, 3, 4, 5, and 6 of treatment, and at 1-week, 4-weeks and 12-weeks post-treatment.
Secondary outcomes (1)
Change in scores on the Beck Scale for Suicide Ideation (BSI)
The investigators will evaluate the changes in suicidal thinking scores before, during, and after rTMS treatment. BSI scores range from 0 to 38, with higher scores indicating greater suicidal ideation (worse outcome).
Measured: Baseline, end of weeks 1, 2, 3, 4, 5, and 6 of treatment, and at 1-week, 4-weeks and 12-weeks post-treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2021
- Study start14 Jan 2021
- Primary completion14 Jan 2027 (estimated)
- Study completion14 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Autism Spectrum DisorderStudies of the same condition, open and under way.
- More trials run by Centre for Addiction and Mental HealthThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre for Addiction and Mental Health
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Stephanie Ameis, Centre for Addiction and Mental Health
- Investigators
- Stephanie H Ameis, MD, MSC, Principal investigator, Centre for Addiction and Mental Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04972136
- Sponsor's protocol ID
- 141/2019
- Acronym
- rTMS-MDD
- Status last verified
- Mar 2026
- First submitted
- 26 May 2021
- Last updated
- 19 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-Blind Randomized Controlled Trial Evaluating the Efficacy of Repetitive Transcranial Magnetic Stimulation (rTMS) as Treatment for Major Depressive Disorder in Transition-Age Youth With Autism Spectrum Disorder
- ClinicalTrials.gov ID
- NCT04972136
- Acronym / sponsor ID
- rTMS-MDD / 141/2019
- Keywords
- Autism Spectrum Disorder, Major Depressive Disorder, rTMS (Repetitive Transcranial Magnetic Stimulation), MRI (Magnetic Resonance Imaging), Suicidal and Self-Injurious Behaviour, Adaptive Functioning
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Centre for Addiction and Mental HealthUniversity, hospital or other
- Study start
- 14 Jan 2021 (actual)
- Primary completion
- 14 Jan 2027 (estimated)
- Study completion
- 14 Jan 2027 (estimated)
- First posted
- 22 Jul 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The current clinical trial is focused on evaluating the efficacy of rTMS for treatment of depression in youth and young adults (hereafter called transition aged youth, TAY) with autism spectrum disorder (ASD). The motivation to undertake the current efficacy study is driven by: (1) the substantial impact of depression on TAY with ASD (based on prevalence and contribution to disability/impairment); (2) lack of evidence-based treatments for depression in autism (there are no current trials rigorously evaluating any treatment for depression, i.e., psychotherapeutic, pharmacotherapeutic, brain stimulation); (3) rTMS has demonstrated efficacy in non-autistic individuals to improve symptoms of depression and may be better tolerated in youth than medication treatment; (4) a prior pilot rTMS study focused on treatment of executive function deficits in autism indicated that high frequency rTMS delivered using a rigorous randomized control trial (RCT) protocol can be feasibly implemented in TAY with autism, is well tolerated (mild to moderate adverse effects and low drop out), and has the potential to improve symptoms of depression.
Detailed description
The investigators will use a randomized, double-blind, sham-controlled design of bilateral theta burst stimulation (BL-TBS) to dorsolateral prefrontal cortex (DLPFC) administered 5 days per week for 6 weeks (30 sessions). The investigators will recruit n=80, 16-35 year old participants with autism that do not have co-occurring intellectual disability (ID). In the current study, the target population will be individuals with autism, without ID who have co-occurring clinically significant depression. Pre/post treatment MRI will be used to study mechanisms of treatment response. The investigators will build on their previous pilot rTMS study in autism with two key innovations. First, the investigators will use theta burst stimulation (TBS) for depression as opposed to conventional rTMS. TBS is a newer form of rTMS shown to be non-inferior to conventional rTMS for depression with a similar safety profile. Tolerance of intermittent TBS (iTBS, delivered at 100% RMT to right DLPFC in ten 9-17 year-olds with ASD) has already been shown in autism in a prior open-label study. Importantly, TBS can be delivered in a fraction of the time needed for conventional rTMS. This shorter administration time may be critical for participant retention as sensory sensitivity is a major feature of autism. A shorter administration also has important practical implications for future clinical access. The investigators will use BL-TBS based on: preliminary data of improved antidepressant efficacy with a bilateral (over unilateral) TBS approach that combines left excitatory with right inhibitory DLPFC stimulation, as well as findings that bilateral (over unilateral) rTMS may improve suicidal ideation in MDD.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active bilateral theta burst stimulation | Active comparator | Device: Active Bilateral Theta Burst StimulationAn X100 stimulator with a B65 A/P type coil (Magventure Inc.) will be used. The coil is positioned under MRI guidance using real-time neuronavigation using Brainsight [x,y,z= -38, 44, 26(left), +38, 44, 26 (right). BL-TBS will be delivered at 90% RMT, corrected for scalp to cortex distance, to targeted left and right DLPFC sites, differing only in stimulation pattern and total number of pulses (triplet 50 Hz bursts, repeated at 200 msec (i.e., 5 Hz); right DLPFC (continuous TBS, cTBS): 120 seconds uninterrupted bursts (total of 600 pulses); left DLPFC (intermittent TBS, iTBS: 2 seconds on and 8 seconds off; 600 pulses per session; total duration of 3 min 9 seconds/hemisphere). |
| Sham bilateral theta burst stimulation | Sham comparator | Device: Sham Bilateral Theta Burst StimulationAn X100 stimulator with a B65 A/P type coil (Magventure Inc.) will be used with the active coil facing away from the scalp, for sham stimulation. The coil is positioned under MRI guidance using real-time neuronavigation using Brainsight [x,y,z= -38, 44, 26(left), +38, 44, 26 (right). To reproduce the nociceptive qualities of the stimulation, the B65-type stimulation coil - sham side - includes a built in electrical stimulator in the coil connector which "fires" a synchronous electrical pulse along with the TMS stimulus through electrodes mounted on the forehead or near the area of stimulation, to generate auditory and somatosensory (vibration) stimuli. |
Who may qualify
- Ages
- 16 to 35 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- Fluent in English
- ASD diagnosis confirmed by the clinician/clinical team, and IQ> or =70
- Able to participate in the informed consent process, provide voluntary informed consent and provide a spontaneous narrative description of the key elements of the study
- Clinical stability: determined by a physician, no switch of psychotropic medications or increase in dosage in the last 30 days; no change in other therapeutic interventions in last 30 days
- BDI-II score ≥21 that is sustained over a lead-in period of two weeks
Key exclusion criteria (8 listed)
- A history of a DSM-5 substance use disorder (other than tobacco) within the past six months; or a positive baseline urine drug screen
- Significantly debilitating medical or neurologic illness, or acute or unstable medical illnesses as determined by study physician
- Metal implants or a pace-maker, claustrophobia that would preclude the MRI scan
- Actively suicidal (i.e., suicidal ideation with plan and intent) or high risk for suicide as assessed by a study psychiatrist
- History of seizures
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Active Bilateral Theta Burst StimulationAlso: X100 with a B65-type coil (Magventure Inc.)A total of 30 active BL-TBS sessions. Stimulation will begin with right DLPFC (cTBS) followed by left DLPFC (iTBS) | Device | Active bilateral theta burst stimulation |
| Sham Bilateral Theta Burst StimulationAlso: X100 with a B65-type coil (Magventure Inc.)A total of 30 sham BL-TBS sessions. Stimulation will begin with right DLPFC (cTBS) followed by left DLPFC (iTBS) | Device | Sham bilateral theta burst stimulation |
Primary outcome
Change in scores on the 17-item Hamilton Rating Scale for Depression (HRSD-17)
Time frame: Baseline, end of weeks 1, 2, 3, 4, 5, and 6 of treatment, and at 1-week, 4-weeks and 12-weeks post-treatment.
The investigators will evaluate the changes in the severity of symptoms of depression before, during, and after rTMS treatment. HRSD-17 scores range from 0 to 52, with higher scores indicating greater severity of depressive symptoms (worse outcome).
1 secondary outcome
Change in scores on the Beck Scale for Suicide Ideation (BSI)
Time frame: Baseline, end of weeks 1, 2, 3, 4, 5, and 6 of treatment, and at 1-week, 4-weeks and 12-weeks post-treatment.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Mar 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Stephanie H Ameis, MD, MSC principal investigator
Centre for Addiction and Mental Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Active Bilateral Theta Burst Stimulation in people with Autism Spectrum Disorder and Major Depressive Disorder, run by Centre for Addiction and Mental Health at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 19 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Viviane Grassmann, PhD (416-535-8501 ext. 30795, AutismTMS@camh.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in scores on the 17-item Hamilton Rating Scale for Depression (HRSD-17) (time frame: Baseline, end of weeks 1, 2, 3, 4, 5, and 6 of treatment, and at 1-week, 4-weeks and 12-weeks post-treatment.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Mar 2026.