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

6 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a device that sends electrical signals to the brain to help children with autism who hurt themselves and don't get better with usual treatments. The device aims to calm the brain areas causing these behaviors. This method has shown promise in treating autism by improving behavior.

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 data supports the effectiveness of the treatment Deep Brain Stimulation (DBS) for autism?

Research shows that DBS has been effective in improving symptoms of autism, such as self-injurious behavior and obsessive-compulsive symptoms, especially in cases where other treatments have failed. In a case report, DBS targeting the basolateral amygdala improved emotional, social, and cognitive symptoms in a patient with autism over 24 months. ^{1 2 3 4 5}

Is deep brain stimulation (DBS) generally safe for humans?

Deep brain stimulation (DBS) has been used in humans for various conditions, and while it can be beneficial, it does come with some risks. Common complications include infections, lead migrations (movement of the wires), and device malfunctions, with some cases requiring additional surgery. However, these risks can be managed, and further research is ongoing to improve safety. ^{1 6 7 8 9}

How does deep brain stimulation differ from other treatments for autism?

Deep brain stimulation (DBS) is unique because it involves applying electrical impulses directly to specific areas of the brain to improve symptoms, unlike other treatments that typically involve medication or behavioral therapy. DBS is particularly considered for severe cases of autism with symptoms like self-injurious behavior that do not respond to traditional treatments. ^{1 2 3 10 11}

Research Team

George Ibrahim, MD

Principal Investigator

The Hospital for Sick Children

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

References

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

Deep brain stimulation for autism spectrum disorder. [2023]

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

Effectiveness and safety of deep brain stimulation for patients with refractory obsessive compulsive disorder and comorbid autism spectrum disorder; A case series. [2022]

3. Switzerland 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. [2021]

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

Deep brain stimulation for extreme behaviors associated with autism spectrum disorder converges on a common pathway: a systematic review and connectomic analysis. [2022]

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

Update on deep brain stimulation. [2019]

6. Austria pubmed.ncbi.nlm.nih.gov

Complications of deep brain stimulation in Parkinson's disease: a single-center experience of 517 consecutive cases. [2023]

7. United States 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. [2023]

8. United States 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. [2022]

9. Spain pubmed.ncbi.nlm.nih.gov

Intracerebral abscess: a rare complication of Deep Brain Stimulation. [2013]

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

Deep brain stimulation for severe autism: from pathophysiology to procedure. [2015]

11. Austria 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. [2018]