Comparing Sertraline and Placebo for Treating Anxiety in Children with Neurodevelopmental Disorders

A Randomized Placebo-Controlled Trial of Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders

This study is testing if the medication sertraline can help reduce anxiety in children and teens aged 8-17 with neurodevelopmental disorders like autism and Fragile X syndrome compared to a placebo.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 130 (estimated)
• Ages: 8 Years to 17 Years
• Sex: All
• Sponsor: Holland Bloorview Kids Rehabilitation Hospital (Academic / other)
• Locations: 8 sites (Calgary, Alberta and 7 other locations)
• Trial ID: NCT06081348 on ClinicalTrials.gov

What this trial studies

This pilot study aims to evaluate the effectiveness of sertraline, a selective serotonin reuptake inhibitor, in reducing anxiety symptoms in children and adolescents aged 8-17 with neurodevelopmental disorders such as autism and Fragile X syndrome. Participants will be randomly assigned to receive either sertraline or a placebo, and the study will assess the impact on anxiety levels using both transdiagnostic and diagnosis-specific measures. The goal is to gather preliminary data that could inform larger-scale clinical trials in the future.

Who should consider this trial

Good fit: Ideal candidates are outpatients aged 8-17 who have a diagnosis of a neurodevelopmental disorder and meet criteria for an anxiety disorder.

Not a fit: Patients who do not have a neurodevelopmental disorder or an anxiety disorder may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to an approved treatment for anxiety in children and adolescents with neurodevelopmental disorders.

How similar studies have performed: While sertraline has shown effectiveness in treating anxiety in the general pediatric population, this specific application in neurodevelopmental disorders is novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

1. Outpatients 8-17 years of age, inclusive
2. Females of child bearing potential who are sexually active and agree to use medically acceptable birth control throughout the study and at least one week post last dose of study drug.
3. Meet Diagnostic and Statistical Manual of Mental Disorders - DSM-5 criteria for ASD, ADHD, Tic Disorders, or genetic diagnosis of Fragile X, tuberous sclerosis or 22q11 deletions.
4. Meet DSM-5 criteria for one of the following anxiety disorders: Separation Anxiety Disorder, Social Anxiety Disorder, Agoraphobia, Generalized Anxiety Disorder, or Unspecified Anxiety Disorder, based on expert clinical interview, supported by the Kiddie Schedule for Affective Disorders and Schizophrenia (KSADS; Kaufman et al., 2016). Other specified anxiety disorder is included to account for youth with impairing anxiety symptoms who may not meet criteria for one of the other anxiety disorders.
5. Have a Clinician's Global Impression-Severity for anxiety (CGI-S; Guy, 1976)) score ≥ 4 (moderately ill) (inter-rater reliability will be done prior to initiation of enrollment, using videotapes of interviews and vignettes)
6. Have at least phrase speech, to allow for some self-report. So that results can be generalized to children and youth with NDD and various levels of ability, no IQ cut-off will be employed. Full-scale IQ (as measured by the Stanford-Binet) is measured to explore its effect on efficacy and safety\*
7. If already receiving interventions, must meet the following criteria:

   1. If receiving concomitant medications affecting behaviour, must be on a stable dose during the month prior to screening and will not electively modify ongoing medications for study duration
   2. If already receiving stable non-pharmacological behavioural interventions, have stable participation during 3 months prior to screening, and will not electively modify ongoing interventions
8. Ability to complete assessments in English/French

Exclusion Criteria:

1. Receiving other SSRIs within four weeks of randomization (6 weeks for fluoxetine)
2. Previous treatment with sertraline, at an adequate dose (at least 100mg for 6 weeks, or lower dose and duration if not well-tolerated), associated with no response or significant-to-the-participant side effects.
3. Received more than 2 previous appropriate trials of SSRIs with no adequate response
4. Pregnant females or sexually active females on inadequate contraception
5. Serious medical condition that, based on Investigator judgment, might interfere with the conduct of the study, confound interpretation of the study results, or endanger participant. In addition diabetic patients on medications for glycemic control will be excluded as sertraline may interfere with glycemic control.
6. Hypersensitivity to sertraline or any components of its formulation
7. On Monoamine Oxidase Inhibitors or pimozide (as per product monograph)
8. On concomitant medications known to significantly increase QT interval where this would result in unacceptable risk per Investigator judgment.
9. Known congenital QT prolongation
10. HIV, hepatitis B or C, hemophilia, abnormal blood pressure, substance abuse, immunity disorder, major depressive episode or psychosis (as required by Health Canada)
11. Unable to tolerate venipuncture
12. Unable to swallow capsules
13. Enrolled in another intervention study

Where this trial is running

Calgary, Alberta and 7 other locations

• Alberta Children's Hospital - University of Calgary — Calgary, Alberta, Canada (Recruiting)
• University of Alberta-Glenrose — Edmonton, Alberta, Canada (Recruiting)
• Dalhousie University - IWK Health Centre — Halifax, Nova Scotia, Canada (Recruiting)
• McMaster University — Hamilton, Ontario, Canada (Recruiting)
• Queen's University — Kingston, Ontario, Canada (Not_yet_recruiting)
• University of Western Ontario, Lawson Health Research Institute — London, Ontario, Canada (Recruiting)
• Holland Bloorview Kids Rehabilitation Hospital — Toronto, Ontario, Canada (Recruiting)
• Ste Justine Hospital - Universite de Montreal — Montreal, Quebec, Canada (Not_yet_recruiting)

Study contacts

• Principal investigator: Dr. Evdokia Anagnostou — Holland Bloorview Kids Rehab Hospital
• Study coordinator: Faiza Khawaja

Conditions Neurodevelopmental Disorders; Autism; Autism Spectrum Disorder; Fragile X Syndrome; Tuberous Sclerosis; 22Q11 Deletion Syndrome; 22Q11 Deletion; ADHD