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

Anagnostou, Evdokia, M.D.

Status and phase: Enrolling; Phase 2

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

Treatments: Other: Placebo; Drug: Sertraline

Study type: Interventional

Funder types: Other

Identifiers

NCT06081348

SER-11-2020

Details and patient eligibility

About

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.

Enrollment: 130 estimated patients

Sex: All

Ages: 8 to 17 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

130 participants in 2 patient groups, including a placebo group

Sertraline

Active Comparator group

Treatment:

Drug: Sertraline

Placebo

Placebo Comparator group

Treatment:

Other: Placebo