Trial With the Treatment of Sertraline in Youth With Generalized, Separation and/or Social Anxiety Disorders.

Study Overview
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Brief Summary
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A Multicenter, acute, randomized, double-blind, placebo-controlled, flexible-dose trial with the treatment of sertraline.

Detailed Description
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Randomized, double-blind, placebo-controlled trial of an evidence-based antidepressant, sertraline, in youth (N=120) with generalized, separation and/or social anxiety disorders, seeks to evaluate the predictive value of plasma EV signatures. Patients will be randomized to sertraline (25-200 mg/day) or placebo (3:1) and total plasma EVs will be collected at baseline and serially during the course of the 12-week treatment period.

Official Title
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Extracellular Vesicles as Predictors of Antidepressant Outcomes in Pediatric Anxiety (EV-SOPRANO)

Conditions
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Anxiety Disorders

Intervention / Treatment
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* Drug: sertraline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for Patients with Anxiety : Written, informed assent and consent. Patients, parent/guardian/LAR must be fluent in the English. 8-17 years of age, inclusive, at Visit 1, and who have a parent/guardian/LAR. Patients must meet DSM-5 criteria for generalized, social and/or separation anxiety disorder, confirmed by the MINI-KID with no lifetime history of mania, OCD or significant history of trauma exposure. PARS score ≥15 at Visits 1 and 2. Caregiver who is willing to consent to be responsible for safety monitoring of the patient, provide information about the patient's condition, oversee the administration of the investigational product. No clinically significant abnormalities on physical examination. Negative pregnancy test at Visit 1 in females. Sexually active patients must practice a reliable method of contraception (Section 15.0) that will continue for the duration of the study and within 30 days following the end of study participation. Reliable methods of contraception are defined below; other forms of contraceptives (pharmacological and/or non-pharmacological) are not accepted. surgical sterilization oral contraceptives (e.g., estrogen-progestin combination or progestin) transdermally-delivered contraceptives (e.g., Ortho-Evra), depot injections (e.g., Depo-Provera) vaginal contraceptive ring (e.g., NuvaRing), contraceptive implants (e.g., Implanon, Norplant II/Jadelle) an intrauterine device or diaphragm plus condom. Inclusion Criteria for Healthy Controls: Written, informed assent and consent. Patients, parent/guardian/LAR must be fluent in the English. 8 to 17 years of age, inclusive, at Visit 1, and who have a parent/guardian/LAR. No history of any DSM-5 disorders (nicotine use disorder is permitted, history of adjustment disorder is permitted), confirmed by the MINI-KID. Caregiver who is willing to consent to be responsible for safety monitoring of the patient, provide information about the patient. No clinically significant abnormalities on physical examination. Negative pregnancy test at Screening in females. Negative urine drug screen at Screening. No first-degree relatives with an affective, anxiety or psychotic disorder. Exclusion Criteria for Patients with Anxiety Disorders and Healthy Comparison: Subjects Co-occurring DSM-5 diagnosis mood (except persistent depressive disorder, unspecified depressive disorder or co- occurring anxiety disorders, provided that the primary diagnosis is generalized, social and/or separation anxiety disorder(s)), eating, bipolar, or psychotic disorders. A history of treatment with SSRIs within 12 weeks of Visit 2 (Baseline) or current pharmacotherapy with CNS effects that require >5 half-lives for discontinuation. A history of major neurological or medical illness or head trauma with loss of consciousness for ≥5 minutes. Lifetime history of mania, OCD, or significant history of trauma exposure. History of hypersensitivity to sertraline. Lifetime diagnosis of intellectual disability or history of IQ <70. History of alcohol/substance use disorder or any substance abuse within the past 6 months (nicotine dependence is permitted). Current psychotherapy stable for <2 months prior to Visit 2 (Baseline). Females will not be eligible to participate if they are pregnant, breast feeding or lactating. The subject lives >100 miles from the University of Cincinnati or >90 minutes from the CU site or is not able to attend the follow-up visits. Patients who are unable to swallow capsules. Is currently considered at risk of suicide in the opinion of the investigator, represents an inappropriate risk to the participant and/or could confound the interpretation of the study results.

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: During the acute treatment phase, 90 patients will be randomized to sertraline and 30 patients will be randomized to placebo (3:1).
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: sertraline<br>90 patients will be randomized to sertraline | Drug: sertraline<br>* Sertraline is an antidepressant in a group of drugs called selective serotonin reuptake inhibitors (SSRIs)<br>* Other names: Zoloft;|
| Placebo Comparator: Placebo<br>30 patient will be randomized to placebo | Drug: sertraline<br>* Sertraline is an antidepressant in a group of drugs called selective serotonin reuptake inhibitors (SSRIs)<br>* Other names: Zoloft;|
| No Intervention: Healthy Control<br>30 healthy comparison subjects will be followed over the course of 12 weeks | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Clinical Global Impression-Improvement Scale ≤ 2 | Primary response outcome will be treatment response based on patients having attained a score on the Clinical Global Impression-Improvement Scale ≤ 2 at Week 12 or Last-Observation-Carried-Forward (LOCF). | Week 12 |