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

Study Purpose

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.#46; 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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.

An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.

Searching Both is inclusive of interventional and observational studies.

Eligible Ages 8 Years - 17 Years
Gender All
More Inclusion & Exclusion 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.
CALM Study Page 13 of 38 Version 5.0 June 26th, 2023. 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

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.


Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Anagnostou, Evdokia, M.D.
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Evdokia Anagnostou
Principal Investigator Affiliation Holland Bloorview Kids Rehab Hospital
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Overall Status Not yet recruiting
Countries Canada

The disease, disorder, syndrome, illness, or injury that is being 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, Provisional Tic Disorder, Anxiety, Anxiety Disorders, Agoraphobia, Generalized Anxiety, Generalized Anxiety Disorder, Social Anxiety, Social Anxiety Disorder, Unspecified Anxiety Disorder, Other Specified Anxiety Disorders, Separation Anxiety
Arms & Interventions


Active Comparator: Sertraline

Placebo Comparator: Placebo


Drug: - Sertraline

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

Other: - Placebo

Oral placebo capsule

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

International Sites

Calgary, Alberta, Canada



Alberta Children's Hospital - University of Calgary

Calgary, Alberta,

Site Contact

Paul Arnold

[email protected]


University of Alberta-Glenrose, Edmonton, Alberta, Canada



University of Alberta-Glenrose

Edmonton, Alberta,

Site Contact

Francois Bolduc

[email protected]


Dalhousie University - IWK Health Centre, Halifax, Nova Scotia, Canada



Dalhousie University - IWK Health Centre

Halifax, Nova Scotia,

Site Contact

Megan Thomas

[email protected]


McMaster University, Hamilton, Ontario, Canada



McMaster University

Hamilton, Ontario, L8S4K1

Site Contact

Alessia Greco

[email protected]


Queen's University, Kingston, Ontario, Canada



Queen's University

Kingston, Ontario, K7M8A6

Site Contact

Ramona Rego

[email protected]

6135484417 #1165

London, Ontario, Canada



University of Western Ontario, Lawson Health Research Institute

London, Ontario, N6A 5W9

Montréal, Quebec, Canada



Ste Justine Hospital - Universite de Montreal

Montréal, Quebec,

Site Contact

Baudouin Forgeot D'Arc

[email protected]


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