Neurodevelopmental DisordersPhase 2CALMNCT06081348
Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
A Phase 2 study testing Sertraline in people with Neurodevelopmental Disorders and Autism, run by Holland Bloorview Kids Rehabilitation Hospital at 7 sites in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 8 to 17 years
- Conditions the study is for
- Neurodevelopmental Disorders, Autism, Autism Spectrum Disorder
- What is being tested?
- Sertraline
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 130 participants
- Where
- 7 sitesCanada
- Study dates
- 16 Sep 2024to Sep 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Outpatients 8-17 years of age, inclusive
- 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.
- 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.
- 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.
- 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)
- If already receiving interventions, must meet the following criteria:
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- 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
- If already receiving stable non-pharmacological behavioural interventions, have stable participation during 3 months prior to screening, and will not electively modify ongoing interventions
- Ability to complete assessments in English
Who cannot join
- Receiving other SSRIs within four weeks of randomization (6 weeks for fluoxetine)
- 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.
- Received more than 2 previous appropriate trials of SSRIs with no adequate response
- Pregnant females or sexually active females on inadequate contraception
- 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.
- Hypersensitivity to sertraline or any components of its formulation
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- On Monoamine Oxidase Inhibitors or pimozide (as per product monograph)
- On concomitant medications known to significantly increase QT interval where this would result in unacceptable risk per Investigator judgment.
- Known congenital QT prolongation
- HIV, hepatitis B or C, hemophilia, abnormal blood pressure, substance abuse, immunity disorder, major depressive episode or psychosis (as required by Health Canada)
- Unable to tolerate venipuncture
- Unable to swallow capsules
- Enrolled in another intervention study
Trial locations and contacts
7 sites in 1 country. Contact the study team or a site near you to ask about taking part.
7 sites in 1 country
Canada7 sites, 6 recruiting
- Recruiting
Alberta Children's Hospital - University of Calgary
Calgary, Alberta
Noah Furlani, furlani.noah@ucalgary.ca
Dr. Kara Murias
- Recruiting
University of Alberta-Glenrose
Edmonton, Alberta
Keneizha Rubanarayana, metcoord@ualberta.ca
Dr. Francois Bolduc
- Active, not recruiting
Dalhousie University - IWK Health Centre
Halifax, Nova Scotia
- Recruiting
McMaster University
Hamilton, Ontario, L8S4K1
Lavaneyaa Sri, 365-833-0109, srisithl@mcmaster.ca
Dr. Elisabetta Trinari
- Recruiting
Queen's University
Kingston, Ontario, K7M8A6
Stamatoula Pasvanis, 613-533-6000 ext. 76923, s.pasvanis@queensu.ca
Dr. Sarosh Khalid-Khan
- Recruiting
University of Western Ontario, Lawson Health Research Institute
London, Ontario, N6A 5W9
Ahsan Ahmad, (519) 685-8500 ext. 74906, ahsan.ahmad@lhsc.on.ca
Dr. Robert Nicolson
- Recruiting
Holland Bloorview Kids Rehabilitation Hospital
Toronto, Ontario, M4G 1R8
Lily He, 4164256220 ext. 6321, lhe@hollandbloorview.ca
Dr. Evdokia Anagnostou
About this study
Official title: A Randomized Placebo-Controlled Trial of Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
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.
- Conditions
- Neurodevelopmental Disorders, Autism, Autism Spectrum Disorder, Fragile X Syndrome, Tuberous Sclerosis, 22Q11 Deletion Syndrome
- Being tested
- Sertraline, Placebo
- Medical subject headings
- Neurodevelopmental Disorders, Autistic Disorder, Autism Spectrum Disorder, Fragile X Syndrome, Tuberous Sclerosis, 22q11 Deletion Syndrome, DiGeorge Syndrome, Attention Deficit Disorder with Hyperactivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SertralineDrug
Also called Sertraline Hydrochloride, Zoloft, Serotonin Reuptake Inhibitor
Oral capsule (25mg, 50mg, 100mg, 200mg)
PlaceboOther
Oral placebo capsule
| Study group | Role | What they receive |
|---|---|---|
| Sertraline | Active comparator | Not described Receives: Drug: Sertraline |
| Placebo | Placebo comparator | Not described Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 16 weeks
Secondary outcomes (5)
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.
Measured: 16 weeks
Adverse events
Adverse events as elicited by the SMURF.
Measured: 16 weeks
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).
Measured: 16 weeks
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.
Measured: 16 weeks
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.
Measured: 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2023
- Study start16 Sep 2024
- Primary completionSep 2027 (estimated)
- Study completionSep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neurodevelopmental DisordersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 130 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Holland Bloorview Kids Rehabilitation Hospital
- Sponsor type
- University, hospital or other
- 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
- Investigators
- Dr. Evdokia Anagnostou, Principal investigator, Holland Bloorview Kids Rehab Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06081348
- Sponsor's protocol ID
- SER-11-2020
- Acronym
- CALM
- Status last verified
- Jul 2026
- First submitted
- 27 Sep 2023
- Last updated
- 27 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Placebo-Controlled Trial of Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
- ClinicalTrials.gov ID
- NCT06081348
- Acronym / sponsor ID
- CALM / SER-11-2020
- Conditions
- Neurodevelopmental Disorders, Autism, Autism Spectrum Disorder, Fragile X Syndrome, Tuberous Sclerosis, 22Q11 Deletion Syndrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 130 participants (estimated)
- Lead sponsor
- Holland Bloorview Kids Rehabilitation HospitalUniversity, hospital or other
- 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)
- Study start
- 16 Sep 2024 (actual)
- Primary completion
- Sep 2027 (estimated)
- Study completion
- Sep 2027 (estimated)
- First posted
- 13 Oct 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sertraline | Active comparator | Drug: Sertraline |
| Placebo | Placebo comparator | Other: Placebo |
Who may qualify
- Ages
- 8 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (9 listed)
- Outpatients 8-17 years of age, inclusive
- 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.
- 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.
- 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.
- 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)
Key exclusion criteria (13 listed)
- Receiving other SSRIs within four weeks of randomization (6 weeks for fluoxetine)
- 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.
- Received more than 2 previous appropriate trials of SSRIs with no adequate response
- Pregnant females or sexually active females on inadequate contraception
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SertralineAlso: Sertraline Hydrochloride, Zoloft, Serotonin Reuptake InhibitorOral capsule (25mg, 50mg, 100mg, 200mg) | Drug | Sertraline |
| PlaceboOral placebo capsule | Other | Placebo |
Primary outcome
The Screen for Child Anxiety Related Emotional Disorders (SCARED) - parent version
Time frame: 16 weeks
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.
5 secondary outcomes
Clinical Global Impressions - Improvement Scale - Global (CGI-I)
Time frame: 16 weeks
Adverse events
Time frame: 16 weeks
Pediatric Quality of Life Inventory (PedsQL)
Time frame: 16 weeks
Whole blood serotonin (5-HT) assessment
Time frame: 16 weeks
Clinical Global Impressions- Improvement Scale (CGI-I) focused on anxiety
Time frame: 16 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2026.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Dr. Evdokia Anagnostou principal investigator
Holland Bloorview Kids Rehab Hospital
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sertraline in people with Neurodevelopmental Disorders and Autism, run by Holland Bloorview Kids Rehabilitation Hospital at 7 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 27 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Faiza Khawaja (4164256220 ext. 3526, fkhawaja@hollandbloorview.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Screen for Child Anxiety Related Emotional Disorders (SCARED) - parent version (time frame: 16 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jul 2026.