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

NCT ID: NCT04623099

Last Updated: 2024-08-29

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 132 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-08
• Study Completion Date: 2026-12-01

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.

Detailed Description

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, the investigators will examine these two dosing strategies in terms of efficacy (Aim 1) and tolerability (Aim 2).

The investigators propose to recruit 132 adolescents (age 12-17 years, inclusive) with generalized, separation and/or social anxiety disorder (pediatric anxiety trial).1 This will allow investigators to evaluate whether pharmacogenetically-guided escitalopram dosing improves efficacy and tolerability in outpatient adolescents aged 12-17 years with anxiety disorders. Eligible patients will be randomized to: (1) standard escitalopram dosing or (2) pharmacogenetically-guided dosing for 12 weeks.

Conditions

Anxiety

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Standard dosing

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

Group Type: OTHER

Escitalopram

Intervention Type: 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.

Pharmacogenetically-guided escitalopram dosing

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.

Group Type: EXPERIMENTAL

Escitalopram

Intervention Type: 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.

Interventions

Escitalopram

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.

Intervention Type: DRUG

Other Intervention Names

Lexapro

Eligibility Criteria

Inclusion Criteria

1. Written, informed assent and consent.

2. Patients, parent/guardian must be fluent in the English.

3. 12 to 17 years of age, inclusive, at Visit 1.

4. Patients must meet DSM-512 criteria for generalized, social and/or separation anxiety disorder, confirmed by the MINI-KID.

5. PARS score ≥15 at Visit 1 and Visit 2.

6. No initiation of psychotherapy within 8 weeks of screening (Visit 1). Current therapy much be stable for ≥2 months prior to baseline (Visit 2).

7. Clinical Global Impressions-Severity (CGI-S) score ≥4 at Visits 1 & 2.

8. 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.

9. No clinically significant abnormalities on physical examination and EKG.

10. Negative pregnancy test at Visit 1 in females.

11. Negative urine drug screen at Visit 1.

12. 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:

1. Surgical sterilization

2. Oral contraceptives (e.g. estrogen-progestin combination or progestin)

3. Transdermally-delivered contraceptives (e.g., Ortho-Evra), depot injections (e.g., Depo-Provera)

4. Vaginal contraceptive ring (e.g., NuvaRing), contraceptive implants (e.g., Implanon, Norplant II/Jadelle)

5. An intrauterine device

6. Diaphragm plus condom. -

Exclusion Criteria

1. 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.

2. A lifetime diagnosis of an intellectual disability.

3. A significant history of trauma exposure.

4. 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.

5. Allergy, intolerance, non-response or hypersensitivity to escitalopram. Major neurological or medical illness or head trauma with ≥5 minutes loss of consciousness.

6. Alcohol or substance use disorder within the past 6 months (nicotine use is permitted).

7. Psychotherapy initiated within 8 weeks of screening (Visit 1), or plans to initiate/change therapy during the study.

8. Pregnant, breastfeeding, lactating, and/or planning to become pregnant during the study or within 30 days following the end of study participation.

9. Positive urine pregnancy test.

10. A positive urine drug screen.

11. 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.

12. QTc >450 in males or >460 in females (prolonged QTc based on American Heart Association recommendations for Standardization and Interpretation of the EKG

13. Patients who are unable to swallow capsules.

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

University of Cincinnati

OTHER

Sponsor Role: lead

Responsible Party

Jeffrey Strawn, MD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jeffrey R Strawn, MD

Role: PRINCIPAL_INVESTIGATOR

University of Cincinnati

Laura B Ramsey, PhD

Role: PRINCIPAL_INVESTIGATOR

Children's Mercy Kansas City

Locations

University of Cincinnati, Department of Psychiatry & Behavioral Neuroscience

Cincinnati, Ohio, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Zoe Neptune, BS

Role: CONTACT

neptunza@uc.edu

(513) 558-2866

Heidi K Schroeder, BS

Role: CONTACT

heysehk@uc.edu

(513) 558-4422

Facility Contacts

Zoe A Neptune, BS

Role: primary

neptunza@uc.edu

513-558-2866

Heidi K Schroeder, BS

Role: backup

heysehk@uc.edu

513-558-4422

References

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.

Reference Type: DERIVED

PMID: 34834540 (View on PubMed)

Other Identifiers

R01HD099775

Identifier Type: NIH

Identifier Source: secondary_id

View Link

Strawn PrEcISE

Identifier Type: -

Identifier Source: org_study_id