Pharmacogenetically-guided Escitalopram Treatment for Pediatric Anxiety: Aiming to Improve Safety and Efficacy (PrEcISE)

NCT04623099 | Recruiting Phase 4 DMC FDA Drug

• 2 other identifiers: Strawn PrEcISER01HD099775
• Study Type: interventional
• Target: 132
• Locations: 1 country
• Sites: 1

Brief Summary

This double-blind, 12-week study will consist include132 anxious youth who are randomized (1:1) to standard or pharmacogenetically-guided escitalopram dosing. Block randomization (1:1) will be stratified by sex and metabolizer status.

Conditions

Anxiety

Keywords

Kids; Anxiety

Outcome Measures

Primary Outcomes (1)

• Pediatric Anxiety Rating Scale severity score

  Change from Baseline in Pediatric Anxiety Rating Scale (PARS) severity score. The PARS is a clinician-rated instrument for assessing the severity of anxiety symptoms associated with common anxiety disorders in children and adolescents. The PARS score is derived by summing 5 of the 7 severity/impairment/interference items (2, 3, 5, 6, and 7)

  Baseline to Week 12/Early Termination

Secondary Outcomes (1)

• Tolerability-Activation

  Baseline to Week 12/Early Termination

Study Arms (2)

Standard dosing

OTHER

Patients randomized to standard dosing (std) will initiate escitalopram at 5 mg daily and will then increase to 20 mg/day at week 4.

Drug: Escitalopram

Pharmacogenetically-guided escitalopram dosing

EXPERIMENTAL

Patients randomized to PGx-guided treatment, escitalopram titration will be based on CYP2C19 phenotype and predicted escitalopram exposure. In poor metabolizers (PM), escitalopram will be initiated at 5 mg daily and increased to 10 mg daily at week 4.

Drug: Escitalopram

Interventions

Escitalopram DRUG

Escitalopram is FDA-approved for the treatment of major depressive disorder (MDD) in adolescents (12-17 years of age) and is commonly prescribed for adolescents with anxiety disorders.

Also known as: Lexapro

Pharmacogenetically-guided escitalopram dosing; Standard dosing

Eligibility Criteria

• Age: 12 Years - 17 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Written, informed assent and consent.
• Patients, parent/guardian must be fluent in the English.
• to 17 years of age, inclusive, at Visit 1.
• Patients must meet DSM-512 criteria for generalized, social and/or separation anxiety disorder, confirmed by the MINI-KID.
• PARS score ≥15 at Visit 1 and Visit 2.
• No initiation of psychotherapy within 8 weeks of screening (Visit 1). Current therapy much be stable for ≥2 months prior to baseline (Visit 2).
• Clinical Global Impressions-Severity (CGI-S) score ≥4 at Visits 1 \& 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 and EKG.
• Negative pregnancy test at Visit 1 in females.
• Negative urine drug screen at Visit 1.
• Sexually active patients must practice a reliable method of contraception that will continue for the duration of the study and for a minimum of 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)

You may not qualify if:

• Co-occurring DSM-5 mood disorder (except persistent depressive disorder, unspecified depressive disorder, provided that the primary diagnosis is an anxiety disorder), eating, bipolar or psychotic disorders.
• A lifetime diagnosis of an intellectual disability.
• A significant history of trauma exposure.
• A history of SSRI treatment within 12 weeks of baseline or current treatment with a medication with psychiatric effects that requires \>5 half-lives for washout History of non-response to \>2 SSRIs.
• Allergy, intolerance, non-response or hypersensitivity to escitalopram. Major neurological or medical illness or head trauma with ≥5 minutes loss of consciousness.
• Alcohol or substance use disorder within the past 6 months (nicotine use is permitted).
• Psychotherapy initiated within 8 weeks of screening (Visit 1), or plans to initiate/change therapy during the study.
• Pregnant, breastfeeding, lactating, and/or planning to become pregnant during the study or within 30 days following the end of study participation.
• Positive urine pregnancy test.
• A positive urine drug screen.
• Patient lives \>90 minutes from UC or unable to attend follow-up visits. Suicide risk as determined by either: (1) any suicide attempt within the past 6 months and/or (2) significant risk at Visit 1 (Screening) or Visit 2 (Baseline), as judged by the Investigator.
• QTc \>450 in males or \>460 in females (prolonged QTc based on American Heart Association recommendations for Standardization and Interpretation of the EKG
• Patients who are unable to swallow capsules.

Sponsors & Collaborators

• University of Cincinnati: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

University of Cincinnati, Department of Psychiatry & Behavioral Neuroscience

Cincinnati, Ohio, 45219, United States

RECRUITING

Related Publications (1)

• Strawn JR, Poweleit EA, Mills JA, Schroeder HK, Neptune ZA, Specht AM, Farrow JE, Zhang X, Martin LJ, Ramsey LB. Pharmacogenetically Guided Escitalopram Treatment for Pediatric Anxiety Disorders: Protocol for a Double-Blind Randomized Trial. J Pers Med. 2021 Nov 12;11(11):1188. doi: 10.3390/jpm11111188.

  PMID: 34834540 DERIVED

MeSH Terms

Conditions

Anxiety Disorders

Interventions

Escitalopram

Condition Hierarchy (Ancestors)

Mental Disorders

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Jeffrey R Strawn, MD

  University of Cincinnati

  PRINCIPAL INVESTIGATOR

• Laura B Ramsey, PhD

  Children's Mercy Kansas City

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zoe Neptune, BS

CONTACT

(513) 558-2866; neptunza@uc.edu

Heidi K Schroeder, BS

CONTACT

(513) 558-4422; heysehk@uc.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: double-blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: This randomized, controlled trial compares pharmacogenetically-guided and standard dosing of escitalopram in adolescents (12-17 years of age) with anxiety disorders. In this study, investigators will examine these two dosing strategies in terms of efficacy (Aim 1) and tolerability (Aim 2). Investigators will also evaluate the relationship between pharmacodynamic variables and treatment response.

Study Record Dates

• First Submitted: November 4, 2020
• First Posted: November 10, 2020
• Study Start: March 8, 2021
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: August 29, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)