Deep Brain Stimulation for Self-Harm in Children with Autism

Overseen By George M Ibrahim, MD

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: The Hospital for Sick Children

Disqualifiers: Substance abuse, Cardiac arrhythmias, others

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

20 Participants Needed

Trial Summary

What is the purpose of this trial?

Deep Brain Stimulation for the Treatment of Severe Refractory Self-Injurious Behaviour in Children with Autism Spectrum Disorder: A Randomized Trial To evaluate the effectiveness of deep brain stimulation (DBS) of the nucleus accumbens for the treatment of severe refractory, repetitive self-injurious behavior (SIB) in children with Autism Spectrum Disorder. Secondary objectives are to examine the effects of DBS on subtypes of SIB through functional analysis.

Will I have to stop taking my current medications?

The trial information does not specify whether participants need to stop taking their current medications.

What data supports the effectiveness of the treatment Deep Brain Stimulation for self-harm in children with autism?

Deep Brain Stimulation (DBS) has shown promise in improving self-injurious behavior and core symptoms of autism in some cases, such as a 14-year-old boy who experienced significant clinical improvement after DBS treatment. Additionally, studies have reported improvements in patients with autism and self-injurious behavior who were resistant to other treatments, suggesting DBS could be a valuable option. ^{1 2 3 4 5}

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

Deep brain stimulation (DBS) has been studied for various conditions, including autism and self-injurious behavior, and has shown clinical improvements in some cases. However, more research is needed to fully understand its safety and long-term effects, especially in children. ^{1 3 4 5 6}

How is deep brain stimulation different from other treatments for self-harm in children with autism?

Deep brain stimulation (DBS) is unique because it involves applying electrical impulses directly to specific brain areas, like the nucleus accumbens, to reduce self-harm behaviors, whereas other treatments often rely on medications or behavioral therapies that may not be effective for severe cases. ^{1 2 3 4 6}

Research Team

George Ibrahim

Principal Investigator

The Hospital for Sick Children

Eligibility Criteria

This trial is for children with Autism Spectrum Disorder who engage in severe, repetitive self-injury that hasn't improved with other treatments. Specific details on eligibility criteria are not provided.

Inclusion Criteria

I am between 5 and 17 years old.

DSM-5 diagnosis of Autism Spectrum Disorder

Foreseeable risk of serious future self-harm

Exclusion Criteria

I have heart, lung, kidney, or hormone conditions that could make surgery risky.

Pregnancy

Substance dependence or abuse in the last 6 months, excluding caffeine and nicotine

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Post-operative recovery

Participants undergo a four-week post-operative recovery period after DBS implantation

4 weeks

Treatment Block 1

Participants receive either active DBS or no stimulation for three months

12 weeks

Washout

A two-week period where DBS is turned off for all participants

2 weeks

Treatment Block 2

Participants cross over to the opposite condition (active DBS or no stimulation) for three months

12 weeks

Open-label extension

All participants have their DBS devices activated during an open-label period

Long-term

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Deep Brain Stimulation

Trial Overview The study tests the effect of turning deep brain stimulation (DBS) on or off in the nucleus accumbens area of the brain to see if it reduces self-harm behaviors in these children.

Participant Groups

Group I: Group 1 (DBS ON, then OFF) Active Control 2 Interventions

Group 1: DBS will be switched ON in Block 1 (three months) after the initial four-week post-operative period. The DBS device will then be turned OFF for two weeks ("washout period"). The device will remain OFF in Block 2 (three months).

Group II: Group 2 (DBS OFF, then ON) Placebo Group 2 Interventions

Group 2: DBS will remain OFF in Block 1 (three months) after the initial four-week post-operative period. The device will remain off for two weeks thereafter ("washout period"). DBS will be switched ON in Block 2 (three months).

Deep Brain Stimulation is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Deep Brain Stimulation for:

• Essential tremor
• Parkinson's disease
• Dystonia
• Obsessive-compulsive disorder
• Epilepsy
• Chronic pain
• Stroke-related motor deficits (under investigation)

Approved in European Union as Deep Brain Stimulation for:

• Essential tremor
• Parkinson's disease
• Dystonia
• Obsessive-compulsive disorder
• Epilepsy
• Chronic pain

Approved in Canada as Deep Brain Stimulation for:

• Essential tremor
• Parkinson's disease
• Dystonia
• Obsessive-compulsive disorder
• Epilepsy
• Chronic pain

Who Is Running the Clinical Trial?

The Hospital for Sick Children

Lead Sponsor

Trials

724

Recruited

6,969,000+

Findings from Research

This study is a pilot trial involving 6 children and youth with autism spectrum disorder (ASD) who exhibit severe, refractory self-injurious behaviors (SIB), aiming to assess the safety and feasibility of deep brain stimulation (DBS) targeting the nucleus accumbens (NAcc) over a 12-month period.

The trial will evaluate potential treatment efficacy using various behavioral scales and neuro-imaging techniques, marking the first controlled assessment of DBS in a pediatric population with ASD and SIB, which could inform future comparative studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An open-label prospective pilot trial of nucleus accumbens deep brain stimulation for children with autism spectrum disorder and severe, refractory self-injurious behavior: study protocol. Yan, H., Siegel, L., Breitbart, S., et al.[2022]

Noncontingent matched stimulation (NMS) significantly reduced self-injurious behavior (SIB) in an eight-year-old boy with autism, indicating its potential as an effective intervention.

The study utilized a functional analysis to identify the causes of SIB and a multielement design to compare the effects of NMS against unmatched stimulation, demonstrating that NMS can provide similar sensory benefits without the harmful effects of SIB.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduction of automatically maintained self-injurious behavior utilizing noncontingent matched stimuli. Davis, TN., Dacus, S., Strickland, E., et al.[2019]

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]

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]

Electroconvulsive therapy (ECT) has shown over 90% effectiveness in reducing self-injurious behavior (SIB) in individuals with autism spectrum disorder (ASD), but requires frequent maintenance treatments, highlighting the need for alternative therapies.

Deep brain stimulation (DBS) using high-frequency stimulation at the subthalamic nucleus significantly reduced excessive self-grooming behaviors in two mouse models of ASD, suggesting that DBS could be a potential treatment for intractable SIB in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-Frequency Stimulation at the Subthalamic Nucleus Suppresses Excessive Self-Grooming in Autism-Like Mouse Models. Chang, AD., Berges, VA., Chung, SJ., et al.[2020]

References

1. England pubmed.ncbi.nlm.nih.gov

An open-label prospective pilot trial of nucleus accumbens deep brain stimulation for children with autism spectrum disorder and severe, refractory self-injurious behavior: study protocol. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Reduction of automatically maintained self-injurious behavior utilizing noncontingent matched stimuli. [2019]

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

Deep brain stimulation for autism spectrum disorder. [2023]

4. 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]

5. 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]

6. England pubmed.ncbi.nlm.nih.gov

High-Frequency Stimulation at the Subthalamic Nucleus Suppresses Excessive Self-Grooming in Autism-Like Mouse Models. [2020]