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

Han Yan; Lauren Siegel; Sara Breitbart; Carolina Gorodetsky; Alfonso Fasano; Aliya Rahim; Alvin Loh; Abhaya V Kulkarni; George M Ibrahim

doi:10.1186/s40814-022-00988-3

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

Pilot Feasibility Stud. 2022 Feb 2;8(1):24. doi: 10.1186/s40814-022-00988-3.

Authors

Han Yan^{1

2

3}, Lauren Siegel⁴, Sara Breitbart^{1

4}, Carolina Gorodetsky⁵, Alfonso Fasano^{5

6

7

8}, Aliya Rahim^{4

9}, Alvin Loh^{9

10}, Abhaya V Kulkarni^{1

2

3}, George M Ibrahim^{11

12

13

14}

Affiliations

¹ Division of Neurosurgery, The Hospital for Sick Children, 555 University Avenue, Room 1503, Toronto, ON, M5G 1X8, Canada.
² Institute of Health of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada.
³ Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Canada.
⁴ Neurosciences and Mental Health Program, The Hospital for Sick Children, 555 University Avenue, Room 1503, Toronto, ON, M5G 1X8, Canada.
⁵ Division of Neurology, The Hospital for Sick Children, Toronto, Canada.
⁶ Edmond J. Safra Program in Parkinson's Disease, Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, UHN, Toronto, Ontario, Canada. Division of Neurology, University of Toronto, Toronto, Ontario, Canada.
⁷ Krembil Brain Institute, Toronto, Ontario, Canada.
⁸ CenteR for Advancing Neurotechnological Innovation to Application (CRANIA), Toronto, ON, Canada.
⁹ Surrey Place, Toronto, Ontario, Canada.
¹⁰ Division of Developmental Paediatrics, Department of Paediatrics, University of Toronto, Toronto, Canada.
¹¹ Division of Neurosurgery, The Hospital for Sick Children, 555 University Avenue, Room 1503, Toronto, ON, M5G 1X8, Canada. george.m.ibrahim@gmail.com.
¹² Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Canada. george.m.ibrahim@gmail.com.
¹³ Institute of Biomedical Engineering, University of Toronto, Toronto, Canada. george.m.ibrahim@gmail.com.
¹⁴ Institute of Medical Science, University of Toronto, Toronto, Canada. george.m.ibrahim@gmail.com.

Abstract

Background: Children and youth with autism spectrum disorder (ASD) may manifest self-injurious behaviors (SIB) that may become severe and refractory with limited pharmacologic or behavioral treatment options. Here, 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) for children and youth with ASD and severe, refractory SIB.

Methods: This is a prospective, single-center, single-cohort, open-label, non-randomized pilot trial of 6 patients. Participants will be recruited through specialized behavioral clinics with persistent severe and refractory SIB following standard and intensive interventions. Following NAcc-DBS, participants will be enrolled in the study for 12 months. The primary objectives of the study are safety and feasibility, assessed by rate of recruitment and identification of factors impacting adherence to follow-up and study protocol. Potential treatment efficacy will be assessed by changes in the Children's Yale-Brown Obsessive-Compulsive Scale in ASD (CYBOCS-ASD), the Behavior Problems Index (BPI), the Inventory of Statements about Self-Injury (ISAS) and the Repetitive Behavior Scale-Revised (RBS-R) questionnaires. Additional clinical outcomes will be assessed, including measures of participant and caregiver quality of life, actigraph measurements, and positron emission tomography (PET) changes following DBS.

Discussion: This study will be the first to evaluate the effect of DBS of the NAcc on a pediatric population in a controlled, prospective trial. Secondary outcomes will improve the understanding of behavioral, neuro-imaging, and electrophysiologic changes in children with ASD and SIB treated with DBS. This trial will provide an estimated effect size of NAcc-DBS for severe refractory SIB in children with ASD in preparation for future comparative trials.

Trial registration: Registration on ClinicalTrials.gov was completed on 12 June 2019 with the Identifier: NCT03982888 .

Keywords: Autism spectrum disorder; Children; Deep brain stimulation; Nucleus accumbens; Self-injurious behavior.

Associated data

ClinicalTrials.gov/NCT03982888

Grants and funding

2018 Sandra Brown Health Outcomes Catalyst Grant/hospital for sick children