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

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests deep brain stimulation (DBS), a treatment using small electrical impulses to the brain, to determine if it can reduce severe self-injury in children with Autism Spectrum Disorder. Researchers aim to discover if DBS can effectively manage repetitive self-harming behaviors when other treatments have failed. Eligible participants are children with autism who have a history of self-injury that persists despite previous treatments. The trial will compare two groups: one with the DBS device turned on first and then off, and the other with the device off first and then on, to assess the treatment's impact on behavior. As an unphased trial, this study offers participants 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 participants need to stop taking their current medications.

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

Research shows that Deep Brain Stimulation (DBS) can be safe for children with severe self-harming behavior. In earlier studies, researchers used DBS in children at high risk for self-harm, finding it both safe and feasible. These studies demonstrated that DBS significantly reduced self-harming behaviors without major safety issues.

Since researchers are still testing DBS in children for this condition, more information is needed. However, the safety results from past research offer some reassurance for those considering joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Deep Brain Stimulation (DBS) is unique because it targets the brain directly, offering a new way to help children with autism who engage in self-harm. Unlike current treatments, which might include behavioral therapy or medications like antipsychotics, DBS involves implanting a device that sends electrical impulses to specific areas of the brain. Researchers are excited about DBS because it provides a targeted approach, potentially reducing self-harming behaviors more effectively and quickly than traditional methods. This treatment could revolutionize care by offering a new tool for cases where existing therapies have limited success.

What evidence suggests that deep brain stimulation is effective for self-injurious behavior in children with autism?

Research has shown that deep brain stimulation (DBS) can significantly reduce self-harming behavior in children with autism. This trial will divide participants into two groups to assess DBS effects. Group 1 will have the DBS device switched ON initially and then turned OFF, while Group 2 will start with the device OFF and then have it switched ON. Studies have found that DBS leads to a clear drop in self-harming behaviors, improving overall quality of life. In some cases, DBS has also helped children become more socially adaptable by reducing aggressive behavior. This treatment targets specific brain areas that control behavior, aiming to balance mood and behavior patterns. Early results suggest that DBS could be a promising option for those with severe self-harming behavior that hasn't responded to other treatments. ^{2 3 5 6 7}

Who Is on the Research Team?

George Ibrahim

Principal Investigator

The Hospital for Sick Children

Are You a Good Fit for This Trial?

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

Pregnancy

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

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006322324017840

Deep Brain Stimulation of the Nucleus Accumbens for ... NAc-DBS resulted in significant reductions in SIB and SIB-associated behaviors across multiple standardized scales, concurrent with clinically ...

2. 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 ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8808966/

An open-label prospective pilot trial of nucleus accumbens ... We present the protocol of a prospective, mixed-methods study to assess the safety and efficacy of deep brain stimulation (DBS) of the nucleus accumbens (NAcc)

4. thejns.org thejns.org/view/journals/j-neurosurg/137/3/article-p699.xml

Deep brain stimulation for extreme behaviors associated with ... This study presents a comprehensive synopsis of the evidence for DBS in the treatment of extreme behaviors associated with ASD.

5. 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 ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39645140/

Deep Brain Stimulation of the Nucleus Accumbens for ... This first-in-children phase 1 clinical trial demonstrates the safety and feasibility of NAc-DBS in children with severe, refractory SIB at high risk of ...

7. trialx.com trialx.com/clinical-trials/listings/324356/deep-brain-stimulation-for-severe-self-injurious-behaviour-in-children/

Deep Brain Stimulation for Severe Self-Injurious Behaviour ... After recovery, participants will be randomized to a 3 month block of active stimulation or the DBS will remain off. After a two week washout ...