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

NCT06081348 | Recruiting Phase 2 DMC

• 1 other identifier: SER-11-2020
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 8

Brief 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.

Conditions

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

Outcome Measures

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.

  16 weeks

Secondary Outcomes (5)

• Clinical Global Impressions - Improvement Scale - Global (CGI-I)

  16 weeks

• Adverse events

  16 weeks

• Pediatric Quality of Life Inventory (PedsQL)

  16 weeks

• Whole blood serotonin (5-HT) assessment

  16 weeks

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

  16 weeks

Study Arms (2)

Sertraline

ACTIVE COMPARATOR

Drug: Sertraline

Placebo

PLACEBO COMPARATOR

Other: Placebo

Interventions

Sertraline DRUG

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

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

Sertraline

Placebo OTHER

Oral placebo capsule

Placebo

Eligibility Criteria

• Age: 8 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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)
• 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\*
• If already receiving interventions, must meet the following criteria:
• 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/French

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Holland Bloorview Kids Rehabilitation Hospital: lead
• Azrieli Foundation (Funder): collaborator
• Canadian Institutes of Health Research (Funder): collaborator
• Ontario Brain Institute (Funder): collaborator
• McMaster University: collaborator
• Western University: collaborator
• Queen's University: collaborator
• University of Alberta: collaborator
• Alberta Health services: collaborator
• St. Justine's Hospital: collaborator
• Dalhousie University: collaborator
• Unity Health Toronto: collaborator
• University of Toronto: collaborator
• The Hospital for Sick Children: collaborator
• Maternal, Infant, Child and Youth Research Network (MICYRN): collaborator

Study Sites (8)

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, L8S4K1, Canada

RECRUITING

Queen's University

Kingston, Ontario, K7M8A6, Canada

NOT YET RECRUITING

University of Western Ontario, Lawson Health Research Institute

London, Ontario, N6A 5W9, Canada

RECRUITING

Holland Bloorview Kids Rehabilitation Hospital

Toronto, Ontario, M4G 1R8, Canada

RECRUITING

Ste Justine Hospital - Universite de Montreal

Montreal, Quebec, Canada

NOT YET RECRUITING

MeSH Terms

Conditions

Neurodevelopmental Disorders; Autistic Disorder; Autism Spectrum Disorder; Fragile X Syndrome; Tuberous Sclerosis; 22q11 Deletion Syndrome; DiGeorge Syndrome; Attention Deficit Disorder with Hyperactivity; Tic Disorders; Tourette Syndrome; Anxiety Disorders

Interventions

Sertraline; Selective Serotonin Reuptake Inhibitors

Condition Hierarchy (Ancestors)

Mental Disorders; Child Development Disorders, Pervasive; X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Sex Chromosome Disorders; Chromosome Disorders; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Heredodegenerative Disorders, Nervous System; Hamartoma; Neoplasms; Neoplasms, Multiple Primary; Neoplastic Syndromes, Hereditary; Malformations of Cortical Development, Group I; Malformations of Cortical Development; Nervous System Malformations; Neurocutaneous Syndromes; Neurodegenerative Diseases; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Musculoskeletal Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Lymphatic Abnormalities; Lymphatic Diseases; Hemic and Lymphatic Diseases; Abnormalities, Multiple; Hypoparathyroidism; Parathyroid Diseases; Endocrine System Diseases; Attention Deficit and Disruptive Behavior Disorders; Movement Disorders; Central Nervous System Diseases; Basal Ganglia Diseases; Brain Diseases

Intervention Hierarchy (Ancestors)

1-Naphthylamine; Amines; Organic Chemicals; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Neurotransmitter Agents; Serotonin Agents; Physiological Effects of Drugs

Study Officials

• Dr. Evdokia Anagnostou

  Holland Bloorview Kids Rehab Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Faiza Khawaja

CONTACT

4164256220; fkhawaja@hollandbloorview.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 27, 2023
• First Posted: October 13, 2023
• Study Start: September 16, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: July 16, 2025

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: After publication
• Access Criteria: Through Brain Code

Locations

CA (8)