MRI + cTBS for Catatonia in Autism

Overseen By Sarah Mahler, MS

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Vanderbilt University Medical Center

Must not be taking: TMS contraindicated medications

Disqualifiers: Substance abuse, Major illness, Seizure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

Duration: 1 day

40 Participants Needed

Trial Summary

What is the purpose of this trial?

Despite the significant morbidity and mortality associated with catatonia in autism, no diagnostic research has attempted to identify biomarkers for catatonia. This application will use a participant's own individual brain magnetic resonance image to target the primary motor strip with transcranial magnetic stimulation; to determine if hyper-excitability of the brain directly correlates with symptoms of catatonia and social-emotional impairment in autism. Completion of this project would result in the first study to associate hyper-excitability of the brain with catatonia and core features of autism; findings which are likely to have a significant impact on the health and well-being of autistic individuals.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it excludes those prescribed medication contraindicated in TMS (a type of brain stimulation). It's best to discuss your current medications with the trial team to see if they are allowed.

What data supports the effectiveness of the treatment Continuous Theta Burst Stimulation (cTBS) for catatonia in autism?

Research shows that theta burst stimulation (TBS), including continuous TBS (cTBS), can influence brain activity and has been explored for conditions like autism and depression. While specific data on cTBS for catatonia in autism is limited, studies suggest it may help with brain function issues in autism and mood disorders. ^{1 2 3 4 5}

Is continuous theta burst stimulation (cTBS) safe for humans?

Continuous theta burst stimulation (cTBS) has been studied for conditions like major depressive disorder and bipolar depression, and while its therapeutic effects are mixed, it is generally considered safe for use in humans. ^{1 2 4 5 6}

How is the treatment MRI + cTBS for catatonia in autism different from other treatments?

MRI + cTBS is unique because it combines brain imaging with a non-invasive brain stimulation technique called continuous theta burst stimulation (cTBS), which targets specific brain areas to potentially improve symptoms, unlike traditional treatments like medication or electroconvulsive therapy (ECT) that have broader effects. ^{7 8 9 10 11}

Eligibility Criteria

This trial is for individuals aged 15-40 with Autism Spectrum Disorder (ASD), diagnosed by DSM-5 criteria and ADOS-II assessment. Participants must understand English, be able to give consent or have a guardian who can, and be medically stable. Exclusions include substance abuse history, major medical issues, seizures within the last year, pregnancy/breastfeeding, metal in body/pacemakers/claustraphobia that affect MRI safety.

Inclusion Criteria

I am between 15 and 40 years old.

Subjects and/or guardians must also be fluent in English, diagnosed with ASD based on DSM-5 criteria and Autism Diagnostic Observation Schedule-II (ADOS-II) assessment, and competent to assent to the study based on investigator clinical evaluation

I, or my guardian, can legally agree to participate in the study.

Exclusion Criteria

You have a history of drug or alcohol abuse.

History of concomitant major medical/neurologic illness

MRI scanning also introduces exclusionary criteria for conditions contraindicated to MRI, thus individuals with any bodily metal, history of claustrophobia, or pacemakers will be excluded

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Initial assessments including Bush Francis catatonia rating scale and psychological testing

1 day

1 visit (in-person)

Treatment

Application of continuous theta burst stimulation (cTBS) and measurement of motor evoked potentials

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Continuous Theta Burst

Trial Overview The study aims to find biomarkers for catatonia in autism using individual brain MRIs to guide transcranial magnetic stimulation (cTBS) targeting the motor strip. It will explore if brain hyper-excitability correlates with catatonia symptoms and social-emotional impairment in autistic individuals.

Participant Groups

Group I: Individuals with a diagnosis of autism Experimental Treatment 1 Intervention

Individuals with an autism diagnosis

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

Vanderbilt Kennedy Center

Collaborator

Trials

3

Recruited

160+

Findings from Research

In a pilot study involving 10 male children and adolescents with autism spectrum disorder (ASD), intermittent theta-burst stimulation (iTBS) showed promising improvements in executive function and repetitive behaviors after 15 treatment sessions over 3 weeks.

The iTBS treatment was well tolerated with no serious adverse effects reported, indicating its potential safety as a therapeutic option for addressing cognitive deficits in ASD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent theta-burst transcranial magnetic stimulation for autism spectrum disorder: an open-label pilot study. Abujadi, C., Croarkin, PE., Bellini, BB., et al.[2019]

Continuous theta burst stimulation (cTBS) was found to be safe and well-tolerated in patients with major depressive disorder (MDD) or bipolar depression (BD), with no significant differences in adverse events compared to sham treatment.

However, the meta-analysis of three randomized controlled trials involving 78 participants showed no significant improvement in depression scores or response rates with cTBS compared to sham, indicating that cTBS may not provide a therapeutic advantage for treating major depressive episodes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjunctive continuous theta burst stimulation for major depressive disorder or bipolar depression: A meta-analysis of randomized controlled studies. Cai, DB., Qin, XD., Qin, ZJ., et al.[2023]

The change in motor evoked potential (ΔMEP) measured 15 minutes after continuous theta-burst stimulation (cTBS) of the motor cortex is a significant biomarker that can help distinguish adults with autism spectrum disorder (ASD) from neurotypical individuals, based on a study involving 91 participants.

The effectiveness of ΔMEP as a diagnostic tool is influenced by specific genetic polymorphisms related to neuroplasticity, particularly the brain-derived neurotrophic factor (BDNF) and apolipoprotein E (APOE) genes, suggesting that genetic factors may play a role in the neurophysiological responses observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modulation of motor cortical excitability by continuous theta-burst stimulation in adults with autism spectrum disorder. Jannati, A., Ryan, MA., Block, G., et al.[2023]

In a pilot study involving 13 adults with autism spectrum disorder (ASD), intermittent theta burst stimulation (iTBS) applied over the bilateral posterior superior temporal sulcus (pSTS) showed significant immediate improvements in parent-rated autistic symptoms after 5 days of treatment.

The effectiveness of iTBS on cognitive flexibility and clinical symptoms was influenced by individual factors such as baseline social-communicative impairment, cognitive performance, and concurrent psychotropic medication use, highlighting the need for personalized approaches in future trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

5-day multi-session intermittent theta burst stimulation over bilateral posterior superior temporal sulci in adults with autism-a pilot study. Ni, HC., Lin, HY., Chen, YL., et al.[2022]

Theta burst stimulation (TBS) appears to be safe and tolerable for children and adolescents, with reported adverse events mostly being mild, such as headaches, similar to those seen in adults.

Despite the promising safety profile, there is a lack of long-term studies on TBS in younger populations, highlighting the need for further research to better understand its effects and potential risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review of the Safety and Tolerability of Theta Burst Stimulation in Children and Adolescents. Elmaghraby, R., Sun, Q., Ozger, C., et al.[2023]

In a study involving 25 adults with autism spectrum disorder (ASD), a single session of intermittent theta burst stimulation (iTBS) over the dorsolateral prefrontal cortex (DLPFC) significantly improved reaction times on a neuropsychological test compared to sham stimulation, indicating potential efficacy in enhancing cognitive function.

No significant improvements were observed with iTBS over the posterior superior temporal sulcus (pSTS), and behavioral outcomes showed inconsistent results, suggesting that further research is needed to explore the effects of multiple sessions of iTBS on both neuropsychological and behavioral functions in ASD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Impact of Single Session Intermittent Theta-Burst Stimulation over the Dorsolateral Prefrontal Cortex and Posterior Superior Temporal Sulcus on Adults with Autism Spectrum Disorder. Ni, HC., Hung, J., Wu, CT., et al.[2020]

Catatonia can occur in about 14% of adolescents and young adults with autism, and its symptoms can overlap with those of autism, making diagnosis important when there is a noticeable decline in movement and self-care skills.

Effective treatments for catatonia in individuals with autism include benzodiazepines and electroconvulsive therapy, which can be beneficial in both acute and maintenance phases of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Catatonia in autism: implications across the life span. Kakooza-Mwesige, A., Wachtel, LE., Dhossche, DM.[2021]

A systematic review of 19 neuroimaging studies revealed that traditional motor/behavioral catatonia assessments focus on dopamine-mediated cortical and subcortical motor regions, while the Northoff Catatonia Rating Scale (NCRS) highlights issues in higher-order frontoparietal networks related to GABA and glutamate transmission.

The findings suggest that GABAergic treatments are particularly effective for acute catatonia, emphasizing the need to consider both motor and affective symptoms in understanding and treating catatonia, as originally proposed by Karl Kahlbaum.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Going Back to Kahlbaum's Psychomotor (and GABAergic) Origins: Is Catatonia More Than Just a Motor and Dopaminergic Syndrome? Hirjak, D., Kubera, KM., Wolf, RC., et al.[2021]

A 40-year-old woman with schizoaffective disorder and catatonia showed significant decreases in brain perfusion in key areas (left parietal and motor cortices) during an acute episode, as revealed by a SPECT scan.

Treatment with electroconvulsive therapy (ECT) led to a complete resolution of catatonia and improved depressive symptoms, with follow-up SPECT scans showing restored perfusion in the affected brain regions, suggesting that SPECT imaging could be valuable for tracking treatment responses in catatonia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ECT treatment and cerebral perfusion in Catatonia. Galynker, II., Weiss, J., Ongseng, F., et al.[2016]

In a study of nine patients with catatonia due to schizophrenia or mood disorders, ECT significantly reduced catatonic symptoms, demonstrating its efficacy as a treatment.

Patients with mood disorders required fewer ECT sessions and showed greater clinical improvement, which was associated with increased cerebral blood flow in specific brain regions, unlike those with schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and cerebral blood flow changes in catatonic patients treated with ECT. Escobar, R., Rios, A., Montoya, ID., et al.[2019]

The catatonic syndrome is a complex neurobehavioral disorder that can provide insights into the relationship between motivation and movement, highlighting the importance of understanding its neurobiological underpinnings.

Recent studies suggest that the anterior and midcingulate cortices, along with striatal and thalamic regions, play crucial roles in the catatonic syndrome, which may inform future therapeutic approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cingulate-basal ganglia-thalamo-cortical aspects of catatonia and implications for treatment. Fricchione, G., Beach, S.[2020]

References

1. Brazil pubmed.ncbi.nlm.nih.gov

Intermittent theta-burst transcranial magnetic stimulation for autism spectrum disorder: an open-label pilot study. [2019]

2. 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]

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

Modulation of motor cortical excitability by continuous theta-burst stimulation in adults with autism spectrum disorder. [2023]

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

5-day multi-session intermittent theta burst stimulation over bilateral posterior superior temporal sulci in adults with autism-a pilot study. [2022]

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

A Systematic Review of the Safety and Tolerability of Theta Burst Stimulation in Children and Adolescents. [2023]

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

The Impact of Single Session Intermittent Theta-Burst Stimulation over the Dorsolateral Prefrontal Cortex and Posterior Superior Temporal Sulcus on Adults with Autism Spectrum Disorder. [2020]

7. Germany pubmed.ncbi.nlm.nih.gov

Catatonia in autism: implications across the life span. [2021]

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

Going Back to Kahlbaum's Psychomotor (and GABAergic) Origins: Is Catatonia More Than Just a Motor and Dopaminergic Syndrome? [2021]

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

ECT treatment and cerebral perfusion in Catatonia. [2016]

10. England pubmed.ncbi.nlm.nih.gov

Clinical and cerebral blood flow changes in catatonic patients treated with ECT. [2019]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Cingulate-basal ganglia-thalamo-cortical aspects of catatonia and implications for treatment. [2020]