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RecruitingNCT06081348CALMUpdated Jul 27, 2026

Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders

A Phase 2 interventional study of Sertraline and Placebo in Neurodevelopmental Disorders, Autism and Autism Spectrum Disorder, sponsored by Holland Bloorview Kids Rehabilitation Hospital. Recruiting at 7 sites in Canada. Open to participants aged 8 Years to 17 Years. Per ClinicalTrials.gov, last updated 2026-07-27.

Sponsored by Holland Bloorview Kids Rehabilitation Hospital · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
130
Allocation
Randomized
Ages
8 Years to 17 Years
Sex
All
01

Study summary

There are currently no approved medications for the treatment of anxiety in children and youth with neurodevelopmental disorders (NDDs), both common and rare. Sertraline, a selective serotonin reuptake inhibitor, has extensive evidence to support its use in children's and youth with anxiety but not within NDDs. More research is needed to confirm whether or not sertraline could help improve anxiety in children and youth with common and rare neurodevelopmental conditions. This is a pilot study, in which we plan to estimate the effect size of reduction in anxiety of sertraline vs. placebo. across rare and common neurodevelopmental disorders, and determine the best measure(s) to be used as a primary transdiagnostic outcome measure of anxiety, as well as diagnosis specific measures in future, larger-scale clinical trials of anxiety in NDDs.

02

Conditions studied

  • Neurodevelopmental Disorders
  • Autism
  • Autism Spectrum Disorder
  • Fragile X Syndrome
  • Tuberous Sclerosis
  • 22Q11 Deletion Syndrome
  • 22Q11 Deletion
  • ADHD
  • Tic Disorders
  • Tourette Syndrome
  • Tourette Syndrome in Children
  • Tourette Syndrome in Adolescence
  • ADHD - Combined Type
  • ADHD Predominantly Inattentive Type
  • ADHD, Predominantly Hyperactive - Impulsive
  • Anxiety
  • Anxiety Disorders
03

Who can participate

Ages eligible
8 Years to 17 Years
Sexes eligible
All
Accepts healthy volunteers
No

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. 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
  7. Ability to complete assessments in English

Exclusion criteria

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
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
130 participants (estimated)

Study arms

  • Active comparator
    Sertraline

    Drug: Sertraline

  • Placebo comparator
    Placebo

    Other: Placebo

Interventions

  • DrugSertraline

    Oral capsule (25mg, 50mg, 100mg, 200mg)

    Also known as: Sertraline Hydrochloride, Zoloft, Serotonin Reuptake Inhibitor

  • OtherPlacebo

    Oral placebo capsule

05

What researchers measure

Primary outcomes

  1. The Screen for Child Anxiety Related Emotional Disorders (SCARED) - parent version

    The SCARED is a 41-item measure of anxiety symptoms, with both child and parent versions. The parent version will be used as a primary outcome measure. The minimum overall score is 0 while the maximum overall score is 82. A score greater than or equal to 25 may indicate the presence of an Anxiety Disorder. Higher scores indicate a higher instance of anxiety symptoms while a lower score indicates a lower instance of anxiety symptoms.

    Time frame: 16 weeks

Secondary outcomes

  1. Clinical Global Impressions - Improvement Scale - Global (CGI-I)

    The CGI-I is a clinician reported scale which will be used to examine the effect of sertraline vs. placebo on measures of global function. The CGI-Improvement Scale employs a seven point (1 = very much improved to 7 = very much worse) to determine the participant's improvement in response to treatment.

    Time frame: 16 weeks

  2. Adverse events

    Adverse events as elicited by the SMURF.

    Time frame: 16 weeks

  3. Pediatric Quality of Life Inventory (PedsQL)

    The PedsQL will be used to examine the effect of sertraline vs. placebo on measures of quality of life. The PedsQL is measuring health-related quality of life (HRQOL) in 2- to 18-year-olds. The PedsQL 4.0 Generic Core Scales are multidimensional child self-report and parent-proxy report scales that have been used extensively as an outcome measure, including in ASD. We will use the parent-proxy report scale, and optionally, age-appropriate child self-report scale. Each item is is rated between a 0 (Never a problem) to 4 (Almost always a problem).

    Time frame: 16 weeks

  4. Whole blood serotonin (5-HT) assessment

    A whole blood serotonin assessment will be completed to examine the effect of sertraline vs. placebo on biomarkers of serotonin. 3mL of blood will be drawn at screening and week 16 visits for the purpose of this assessment. High performance liquid chromatography will be performed using fluorometric detection of 5-HT, tryptophan (TRP), and 5-hydroxyindole acetic acid (5-HIAA), using N-methylserotonin as an internal standard. Using this method, 5-HT intra- and inter- assay coefficients of variation are reliably less than 5% and 10%, respectively.

    Time frame: 16 weeks

  5. Clinical Global Impressions- Improvement Scale (CGI-I) focused on anxiety

    The CGI-I is a clinician reported scale which will be used to examine the effect of sertraline vs. placebo on measures of global anxiety. The CGI-Improvement Scale employs a seven point (1 = very much improved to 7 = very much worse) to determine the participant's improvement in response to treatment.

    Time frame: 16 weeks

06

Study locations

6 of 7 sites recruiting
  • Alberta Children's Hospital - University of Calgary
    Calgary, Alberta, Canada
    Recruiting
  • University of Alberta-Glenrose
    Edmonton, Alberta, Canada
    • Keneizha Rubanarayana · Contact · metcoord@ualberta.ca
    • Dr. Francois Bolduc · Principal investigator
    Recruiting
  • Dalhousie University - IWK Health Centre
    Halifax, Nova Scotia, Canada
    Active, not recruiting
  • McMaster University
    Hamilton, Ontario L8S4K1, Canada
    • Lavaneyaa Sri · Contact · srisithl@mcmaster.ca · 365-833-0109
    • Dr. Elisabetta Trinari · Principal investigator
    Recruiting
  • Queen's University
    Kingston, Ontario K7M8A6, Canada
    • Stamatoula Pasvanis · Contact · s.pasvanis@queensu.ca · 613-533-6000
    • Dr. Sarosh Khalid-Khan · Principal investigator
    Recruiting
  • University of Western Ontario, Lawson Health Research Institute
    London, Ontario N6A 5W9, Canada
    • Ahsan Ahmad · Contact · ahsan.ahmad@lhsc.on.ca · (519) 685-8500
    • Dr. Robert Nicolson · Principal investigator
    Recruiting
  • Holland Bloorview Kids Rehabilitation Hospital
    Toronto, Ontario M4G 1R8, Canada
    Recruiting
07

References and documents

Individual participant data

Plan to share: Yes

Supporting information: Study protocol, Sap, Icf

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT06081348
Lead sponsor
Holland Bloorview Kids Rehabilitation Hospital
Collaborators
Azrieli Foundation (Funder), Canadian Institutes of Health Research (Funder), Ontario Brain Institute (Funder), McMaster University, Western University, Queen's University, University of Alberta, Alberta Health services, St. Justine's Hospital, Dalhousie University, Unity Health Toronto, University of Toronto, The Hospital for Sick Children, Maternal, Infant, Child and Youth Research Network (MICYRN)
Responsible party
Sponsor
First posted
Oct 13, 2023
Start date
Sep 16, 2024
Primary completion
Sep 2027 (estimated)
Completion
Sep 2027 (estimated)
Last update
Jul 27, 2026

Study contacts

Faiza Khawaja
Contact
fkhawaja@hollandbloorview.ca
4164256220 ext. 3526
Dr. Evdokia Anagnostou
principal investigator · Holland Bloorview Kids Rehab Hospital

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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