Deep Brain Stimulation for Autism

Overseen By Carolina Gorodetsky, MD

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: The Hospital for Sick Children

Disqualifiers: Substance abuse, Cardiac conditions, Pregnancy, others

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

Compensation: Varies

Number of Visits: 5

Duration: 1 year

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests deep brain stimulation (DBS) to determine if it can reduce repetitive self-injurious behavior in children with autism. DBS involves placing tiny electrodes in the brain to send electrical impulses to specific areas. Researchers aim to assess the safety and potential effectiveness of this approach. Children aged 7-18 with autism who continue to experience self-injury despite medical treatment might be suitable candidates. Participants and their families must commit to a year of follow-ups and appointments. As an unphased trial, this study offers families a unique opportunity to contribute to groundbreaking research that could lead to new treatment options.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the study team to get a clear answer.

What prior data suggests that deep brain stimulation is safe for children with autism?

Research has shown that deep brain stimulation (DBS) is generally safe for patients. One study demonstrated that DBS reduced symptoms of OCD and depression in individuals with autism. Another study found that DBS significantly decreased aggressive and self-harming behaviors, improving social skills and overall daily functioning.

In a different study on children with autism, researchers found that DBS targeting a brain area related to reward and motivation was relatively safe and could enhance quality of life.

These findings suggest that DBS is usually well-tolerated, but individual experiences may vary. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Deep brain stimulation (DBS) is unique because it targets specific brain circuits directly, offering a new approach to managing repetitive self-injurious behaviors in children with autism spectrum disorder (ASD). Unlike standard treatments like behavioral therapies and medications, which often aim to manage symptoms externally or indirectly, DBS involves a precise, electrical stimulation of brain areas involved in emotion and reward processing. Researchers are excited about this treatment because it has the potential to directly modulate brain activity, potentially leading to more effective and rapid improvements in challenging behaviors associated with ASD.

What evidence suggests that deep brain stimulation is effective for autism?

Research shows that deep brain stimulation (DBS), the treatment under study in this trial, may help reduce challenging behaviors in people with autism. Studies have found that DBS can significantly lower aggression and self-harm, improving daily life and social interactions. Initial results also indicate that DBS might lessen symptoms in individuals with both obsessive-compulsive disorder (OCD) and autism. Early findings suggest that DBS could be safe and effective for children and teens with severe aggression and autism. While more research is needed, these findings support the potential of DBS in managing difficult behaviors in autism. ^{1 2 3 5 6}

Who Is on the Research Team?

George Ibrahim, MD

Principal Investigator

The Hospital for Sick Children

Are You a Good Fit for This Trial?

This trial is for children aged 7-18 with Autism Spectrum Disorder who engage in repetitive self-harm and haven't improved after at least 6 months of medical therapy. Participants must have a caregiver able to consent and commit to all study requirements for one year. Exclusions include pregnancy, inability to complete questionnaires in English, potential relocation, certain health risks from surgery, and recent substance abuse.

Inclusion Criteria

You have a condition where you make repetitive movements that can cause self-injury, as determined by your doctor.

Parents or guardians who are informed and can give written consent.

Parents or legal guardians, including caregivers, informed and able to give written consent

Exclusion Criteria

Pregnancy

Unable to communicate adequately in English in order to complete the baseline and follow-up questionnaires.

Likely to relocate away from the study site or move during the study's one year duration

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Surgical Implantation

Surgical implantation of the Medtronic DBS system and stimulation of the nucleus accumbens

1 week

1 visit (in-person)

Treatment

Deep brain stimulation treatment with regular monitoring and adjustments

1 year

Weekly visits from weeks 2-6, bi-weekly from weeks 7-10, monthly from weeks 11-51

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

1 visit (in-person) at 1 year post-surgery

What Are the Treatments Tested in This Trial?

Interventions

• DBS

Trial Overview

The trial tests the safety and potential effectiveness of Deep Brain Stimulation (DBS) on the nucleus accumbens in children with autism who self-harm despite treatment. Six patients will receive surgical implantation of the Medtronic DBS system over a one-year pilot phase I trial without blinding or randomization.

How Is the Trial Designed?

Group I: DBS Treatment Experimental Treatment 2 Interventions

Deep brain stimulation of both limbic and dysfunctional reward processing circuits for treatment of repetitive self injurious behaviours in children with ASD

Who Is Running the Clinical Trial?

The Hospital for Sick Children

Lead Sponsor

Trials

724

Recruited

6,969,000+

Published Research Related to This Trial

A review of 221 unique adverse events related to deep brain stimulation (DBS) devices for Parkinson's disease revealed that the most common complications were infections (16.2%) and lead migrations (8.6%).

Over 40% of the reported adverse events required patients to return to the operating room for device explantation or revision, highlighting the need for further research to improve the safety and reliability of DBS systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterizing Complications of Deep Brain Stimulation Devices for the Treatment of Parkinsonian Symptoms Without Tremor: A Federal MAUDE Database Analysis. Bennett, J., MacGuire, J., Novakovic, E., et al.[2023]

Deep brain stimulation (DBS) has shown potential efficacy in treating treatment-resistant symptoms in individuals with autism spectrum disorder (ASD), particularly for obsessive-compulsive disorder and self-injurious behaviors, based on a review of 13 studies involving 16 patients.

Despite some clinical improvements observed in patients with severe symptoms resistant to multiple drug therapies, the variability in outcomes over time suggests that more extensive research is necessary to fully understand the effectiveness and safety of DBS for ASD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for autism spectrum disorder. Marini, S., D'Agostino, L., Ciamarra, C., et al.[2023]

Deep brain stimulation (DBS) targeting the basolateral amygdala significantly improved self-injurious behavior and core symptoms of autism in a 13-year-old boy over a 24-month follow-up period.

The study suggests that the basolateral amygdala plays a crucial role in the emotional and social aspects of autism, highlighting its potential as a therapeutic target for severe cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DBS in the basolateral amygdala improves symptoms of autism and related self-injurious behavior: a case report and hypothesis on the pathogenesis of the disorder. Sturm, V., Fricke, O., Bührle, CP., et al.[2021]

Deep Brain Stimulation (DBS) for Parkinson's disease can lead to rare complications, such as an intracranial abscess, as demonstrated in a case involving a 59-year-old male who developed significant inflammation and required multiple surgeries after the procedure.

Despite the complications, the patient's Parkinson's symptoms improved after the abscess was surgically drained, suggesting that the abscess may have inadvertently provided some therapeutic benefit similar to a subthalomotomy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracerebral abscess: a rare complication of Deep Brain Stimulation. Brandão, E., Rosas, MJ., Abreu, P., et al.[2013]

A 14-year-old boy with autism spectrum disorder (ASD) and self-injurious behavior showed significant clinical improvement after receiving deep brain stimulation (DBS) targeting the nucleus accumbens, indicating its potential as a treatment for refractory cases.

Imaging studies (FDG-PET and MRI) revealed decreased metabolism and cortical volumes in the prefrontal, frontal, and occipital cortices two years post-DBS, suggesting structural and functional brain changes associated with the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nucleus accumbens deep brain stimulation for a patient with self-injurious behavior and autism spectrum disorder: functional and structural changes of the brain: report of a case and review of literature. Park, HR., Kim, IH., Kang, H., et al.[2018]

Deep brain stimulation (DBS) for Parkinson's disease is generally safe, with a low mortality rate of 0.2% and permanent morbidity at 0.6%, but complications such as intracerebral hemorrhage (ICH) and seizures can occur in a small percentage of cases.

The study found that the type of lead used in DBS can influence complications, with Medtronic's leads associated with higher rates of perielectrode brain edema compared to Boston Scientific's, highlighting the need for further research on hardware design to improve safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complications of deep brain stimulation in Parkinson's disease: a single-center experience of 517 consecutive cases. Servello, D., Galbiati, TF., Iess, G., et al.[2023]

In a study of 181 patients undergoing deep brain stimulation (DBS) surgery for movement disorders, no mortality or permanent morbidity was reported, indicating a high safety profile for the procedure.

The study found that complication rates significantly decreased from 31% in the early period to 10% in the later period, suggesting that surgical experience plays a crucial role in minimizing adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experience Reduces Surgical and Hardware-Related Complications of Deep Brain Stimulation Surgery: A Single-Center Study of 181 Patients Operated in Six Years. Sorar, M., Hanalioglu, S., Kocer, B., et al.[2022]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10251363/

Deep brain stimulation for autism spectrum disorder - PMC

Scientific research on the use of DBS in people with autism has focused this interest mainly on treatment-resistant obsessive-compulsive disorder.

2.

sciencedirect.com

sciencedirect.com/science/article/pii/S1750946723000314

Effectiveness of deep brain stimulation in refractory and ...

In this case series, DBS significantly reduced aggressiveness and self-injury, favoring functionality, social adaptation of the patients, and improving the ...

3.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/34952108/

Effectiveness and safety of deep brain stimulation for ...

Though present results are preliminary, DBS reduced symptoms of OCD and depression in patients with OCD and comorbid ASD.

4.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03982888

Deep Brain Stimulation in Children With Autism

The purpose of this study is to evaluate the safety and possible effectiveness of deep brain stimulation (DBS) of the nucleus accumbens in children with ...

5.

bmcpediatr.biomedcentral.com

bmcpediatr.biomedcentral.com/articles/10.1186/s12887-024-04920-x

Effectiveness of deep brain stimulation on refractory ...

We believe that DBS in intractable aggressiveness in children and adolescents with ASD and severe ID can be safe and effective.

6.

biologicalpsychiatryjournal.com

biologicalpsychiatryjournal.com/pb/assets/raw/Health%20Advance/journals/bps/BPS-250313-Ibrahim_FINAL-1742404156867.pdf

New Pilot Study Shows Deep Brain Stimulation May ...

In this study, we showed that DBS targeting the NAc is relatively safe and may improve quality of life." Researchers performed a regulated, ...