Sertraline Vs. Placebo in the Treatment of Anxiety in Children and AdoLescents with NeurodevelopMental Disorders

Phase 2

Recruiting

• Conditions: Tuberous Sclerosis; ADHD - Combined Type; Anxiety; Autism Spectrum Disorder; 22Q11 Deletion; ADHD; Tic Disorders; Tourette Syndrome; ADHD Predominantly Inattentive Type; Neurodevelopmental Disorders
• Interventions: Other: Placebo; Drug: Sertraline

• Registration Number: NCT06081348
• Lead Sponsor: Anagnostou, Evdokia, M.D.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-09-27
• Study First Submitted QC: 2023-10-11
• Study First Posted: 2023-10-13
• Study Start: 2024-09-16
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-12
• Last Update Posted: 2024-11-14
• Primary Completion: 2026-03
• Study Completion: 2026-03

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 130

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
Sertraline	Sertraline	-

Primary Outcome Measures

Name	Time	Method
The Screen for Child Anxiety Related Emotional Disorders (SCARED) - parent version	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.

Secondary Outcome Measures

Name	Time	Method
Clinical Global Impressions - Improvement Scale - Global (CGI-I)	16 weeks	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.
Clinical Global Impressions- Improvement Scale (CGI-I) focused on anxiety	16 weeks	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.
Adverse events	16 weeks	Adverse events as elicited by the SMURF.
Pediatric Quality of Life Inventory (PedsQL)	16 weeks	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).
Whole blood serotonin (5-HT) assessment	16 weeks	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.

Trial Locations

Locations (8)

Holland Bloorview Kids Rehabilitation Hospital; 🇨🇦 Toronto, Ontario, Canada

Alberta Children's Hospital - University of Calgary; 🇨🇦 Calgary, Alberta, Canada

University of Alberta-Glenrose; 🇨🇦 Edmonton, Alberta, Canada

Dalhousie University - IWK Health Centre; 🇨🇦 Halifax, Nova Scotia, Canada

McMaster University; 🇨🇦 Hamilton, Ontario, Canada

Queen's University; 🇨🇦 Kingston, Ontario, Canada

University of Western Ontario, Lawson Health Research Institute; 🇨🇦 London, Ontario, Canada

Ste Justine Hospital - Universite de Montreal; 🇨🇦 Montréal, Quebec, Canada