Theta Burst Stimulation for Depression and Autism

(RETSORE-RCT Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Rana Elmaghraby, MD

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Children's Hospital Medical Center, Cincinnati

Must not be taking: Anticonvulsants, Barbiturates, Lithium, Benzodiazepines

Disqualifiers: Substance use disorder, Epilepsy, others

No Placebo Group

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

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

Will I have to stop taking my current medications?

You don't have to stop taking your current medications, but you should try to keep them stable during the study. However, if you are currently using anticonvulsant, barbiturate, lithium, or benzodiazepine medications, you cannot participate in the trial.

What data supports the effectiveness of the treatment Theta Burst Stimulation for depression and autism?

Research shows that Theta Burst Stimulation (TBS), a type of transcranial magnetic stimulation (TMS), can be effective for major depressive disorder (MDD). Some studies suggest that different TBS protocols, like intermittent TBS (iTBS) and continuous TBS (cTBS), have shown promise in treating depression, although results can vary. ^{1 2 3 4 5}

Is theta burst stimulation (TBS) safe for humans?

Research shows that theta burst stimulation (TBS) is generally safe and well-tolerated in humans, with most side effects being mild. However, there is a small risk of seizures, so it should be used with caution. ^{5 6 7 8 9}

How is Theta Burst Stimulation (TBS) different from other treatments for depression and autism?

Theta Burst Stimulation (TBS) is a unique form of transcranial magnetic stimulation (TMS) that uses rapid bursts of magnetic pulses to modulate brain activity, potentially offering a faster and more targeted approach compared to traditional repetitive TMS (rTMS). It is being explored for its effectiveness in treating depression and autism, with some studies suggesting it may enhance the effects of existing treatments like medication and psychotherapy. ^{1 2 3 4 5}

Eligibility Criteria

This trial is for individuals with Autism Spectrum Disorder (ASD) who are also experiencing hard-to-treat depression. Participants should be diagnosed with both conditions and have not found relief from standard treatments.

Inclusion Criteria

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

Full-scale intelligence quotient ≥ 70

I am between 13 and 26 years old.

Exclusion Criteria

Actively suicidal (i.e., suicidal ideation with plan and intent) or deemed at high risk for suicide

I have previously undergone rTMS treatment.

For female subjects of childbearing potential, a positive urine pregnancy test

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Treatment

Participants receive either active or sham accelerated theta burst stimulation (aTBS) targeting the left dorsolateral prefrontal cortex, 5 sessions per day for 5 days

1 week

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at 2-week, 6-week, and 12-week intervals

12 weeks

3 visits (in-person)

Open-label extension (optional)

Participants in the sham group who do not show a significant treatment response by the 12-week follow-up are eligible for active, open-label treatment

Treatment Details

Interventions

• Theta Burst Stimulation (Other)

Trial Overview The study is testing the effectiveness of a technique called accelerated theta burst stimulation (aTBS), which uses magnetic fields to stimulate certain areas of the brain, in reducing symptoms of depression in people with ASD.

Participant Groups

Group I: Active TBS Treatment Active Control 1 Intervention

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

Group II: Sham controlled Placebo Group 1 Intervention

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.

Theta Burst Stimulation is already approved in United States for the following indications:

🇺🇸 Approved in United States as Theta Burst Stimulation for:

• Major Depressive Disorder

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Cincinnati Childrens Hospital Medical Center Cincinnati, OH

Who Is Running the Clinical Trial?

Children's Hospital Medical Center, Cincinnati Lead Sponsor

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Treatment of major depression with bilateral theta burst stimulation: a randomized controlled pilot trial. [2018] Current efforts to improve clinical effectiveness and utility of repetitive transcranial magnetic stimulation (rTMS) in the treatment of major depression (MD) include theta burst stimulation (TBS), a patterned form of rTMS. Here, we investigated the efficacy of bilateral TBS to the dorsolateral prefrontal cortex (dlPFC) in patients with MD in additon to ongoing medication and psychotherapy.

2. Netherlands pubmed.ncbi.nlm.nih.gov

Probing changes in corticospinal excitability following theta burst stimulation of the human primary motor cortex. [2017] To determine whether the intensity of transcranial magnetic stimulation (TMS) used to probe changes in corticospinal excitability influences the measured plasticity response to theta burst stimulation (TBS) of the human primary motor cortex.

3. Netherlands pubmed.ncbi.nlm.nih.gov

Adjunctive continuous theta burst stimulation for major depressive disorder or bipolar depression: A meta-analysis of randomized controlled studies. [2023] As a novel type of theta burst stimulation (TBS), continuous TBS (cTBS) has been shown to have mixed therapeutic effects for major depressive disorder (MDD) or bipolar depression (BD). Thus, we performed a meta-analysis of randomized controlled trials (RCTs) of cTBS for treating major depressive episodes in patients with MDD or BD.

4. United States pubmed.ncbi.nlm.nih.gov

Dose-dependence of changes in cortical protein expression induced with repeated transcranial magnetic theta-burst stimulation in the rat. [2016] Theta Burst stimulation (TBS) applied via transcranial magnetic stimulation (TMS) effectively modulates human neocortical excitability but repeated applications of the same TBS protocol at short intervals may be not simply accumulative.

5. Ireland pubmed.ncbi.nlm.nih.gov

Prolonged intermittent theta burst stimulation in the treatment of major depressive disorder: a case series. [2022] Intermittent theta burst stimulation (iTBS) using 600 pulses is an effective and FDA-cleared transcranial magnetic stimulation (TMS) protocol for major depressive disorder (MDD). Prolonged iTBS (piTBS) using 1,800 pulses could increase the effectiveness of TMS for MDD, but its real-world effectiveness is still debated. We assessed the safety, tolerability, and preliminary effectiveness of a 3x daily piTBS 1,800 pulses protocol delivered over 2 weeks in 27 participants. Only four participants (18.2%) achieved response, two of them achieving remission (9.1%). Five participants (18.5%) experienced tolerability issues. Future studies should focus on the neurophysiological effects of TBS protocols to determine optimal parameters.

6. Switzerland pubmed.ncbi.nlm.nih.gov

Safety and tolerability of theta burst stimulation vs. single and paired pulse transcranial magnetic stimulation: a comparative study of 165 pediatric subjects. [2020] Although single- and paired-pulse (sp/pp) transcranial magnetic stimulation (TMS) studies are considered minimal risk in adults and children, the safety profile for theta-burst TMS (TBS) is unknown.

7. United States pubmed.ncbi.nlm.nih.gov

Safety of theta burst transcranial magnetic stimulation: a systematic review of the literature. [2022] Theta burst stimulation (TBS) protocols have recently emerged as a method to transiently alter cortical excitability in the human brain through repetitive transcranial magnetic stimulation. TBS involves applying short trains of stimuli at high frequency repeated at intervals of 200 milliseconds. Because repetitive transcranial magnetic stimulation is known to carry a risk of seizures, safety guidelines have been established. TBS has the theoretical potential of conferring an even higher risk of seizure than other repetitive transcranial magnetic stimulation protocols because it delivers high-frequency bursts. In light of the recent report of a seizure induced by TBS, the safety of this new protocol deserves consideration. We performed an English language literature search and reviewed all studies published from May 2004 to December 2009 in which TBS was applied. The adverse events were documented, and crude risk was calculated. The majority of adverse events attributed to TBS were mild and occurred in 5% of subjects. Based on this review, TBS seems to be a safe and efficacious technique. However, given its novelty, it should be applied with caution. Additionally, this review highlights the need for rigorous documentation of adverse events associated with TBS and intensity dosing studies to assess the seizure risk associated with various stimulation parameters (e.g., frequency, intensity, and location).

8. Croatia pubmed.ncbi.nlm.nih.gov

The acute effects of accelerated repetitive Transcranial Magnetic Stimulation on suicide risk in unipolar depression: preliminary results. [2022] Suicide is a major health concern. Effective acute interventions are lacking. Recent studies have suggested an acute decrease of suicidal ideations following repetitive Transcranial Magnetic Stimulation (rTMS). However, placebo effects could not be excluded. We aimed to evaluate the acute effect of accelerated intermittent theta burst stimulation (TBS) on suicide risk in depression.

9. England pubmed.ncbi.nlm.nih.gov

Safety, tolerability and preliminary evidence for antidepressant efficacy of theta-burst transcranial magnetic stimulation in patients with major depression. [2019] The aim of this open study was to evaluate the safety and tolerability of theta-burst transcranial magnetic stimulation (TBS) and to assess preliminarily its therapeutic efficacy in patients with major depression. A total of 33 patients were assigned to receive one of four TBS protocols for 10 consecutive work days. TBS consisted of triple-pulse 50-Hz bursts given at a rate of 5 Hz to the left or right dorsolateral prefrontal cortex at different stimulation parameters. Severity of depression was assessed by the Hamilton Depression Rating Scale. Our results indicate that TBS as applied in this study is safe and well tolerated in depressed patients and seems to have antidepressant properties. Increase of stimulation parameters is not associated with more side-effects and adds to its therapeutic effect.