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

Primary Purpose

Anxiety

Status
Recruiting
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Escitalopram
Sponsored by
University of Cincinnati
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Anxiety focused on measuring Kids, Anxiety

Eligibility Criteria

12 Years - 17 Years (Child)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • University of Cincinnati, Department of Psychiatry & Behavioral NeuroscienceRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Experimental

Arm Label

Standard dosing

Pharmacogenetically-guided escitalopram dosing

Arm Description

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

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.

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

Tolerability-Activation
Emergence of activation based on the Treatment-Emergent Activation and Suicidality Assessment Profile

Full Information

First Posted
November 4, 2020
Last Updated
September 13, 2023
Sponsor
University of Cincinnati
Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
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1. Study Identification

Unique Protocol Identification Number
NCT04623099
Brief Title
Pharmacogenetically-guided Escitalopram Treatment for Pediatric Anxiety: Aiming to Improve Safety and Efficacy (PrEcISE)
Acronym
PrEcISE
Official Title
Pharmacogenetically-guided Escitalopram Treatment for Pediatric Anxiety: Aiming to Improve Safety and Efficacy (PrEcISE)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 8, 2021 (Actual)
Primary Completion Date
June 30, 2025 (Anticipated)
Study Completion Date
December 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Cincinnati
Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anxiety
Keywords
Kids, Anxiety

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model 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, 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.
Masking
ParticipantInvestigator
Masking Description
double-blind
Allocation
Randomized
Enrollment
132 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Standard dosing
Arm Type
Other
Arm Description
Patients randomized to standard dosing (std) will initiate escitalopram at 5 mg daily and will then increase to 20 mg/day at week 4.
Arm Title
Pharmacogenetically-guided escitalopram dosing
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Escitalopram
Other Intervention Name(s)
Lexapro
Intervention Description
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.
Primary Outcome Measure Information:
Title
Pediatric Anxiety Rating Scale severity score
Description
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)
Time Frame
Baseline to Week 12/Early Termination
Secondary Outcome Measure Information:
Title
Tolerability-Activation
Description
Emergence of activation based on the Treatment-Emergent Activation and Suicidality Assessment Profile
Time Frame
Baseline to Week 12/Early Termination

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Written, informed assent and consent. Patients, parent/guardian must be fluent in the English. 12 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) Vaginal contraceptive ring (e.g., NuvaRing), contraceptive implants (e.g., Implanon, Norplant II/Jadelle) An intrauterine device Diaphragm plus condom. - Exclusion Criteria: 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Zoe Neptune, BS
Phone
(513) 558-2866
Email
neptunza@uc.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Heidi K Schroeder, BS
Phone
(513) 558-4422
Email
heysehk@uc.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeffrey R Strawn, MD
Organizational Affiliation
University of Cincinnati
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Laura B Ramsey, PhD
Organizational Affiliation
Children's Mercy Kansas City
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Cincinnati, Department of Psychiatry & Behavioral Neuroscience
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zoe A Neptune, BS
Phone
513-558-2866
Email
neptunza@uc.edu
First Name & Middle Initial & Last Name & Degree
Heidi K Schroeder, BS
Phone
513-558-4422
Email
heysehk@uc.edu

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
34834540
Citation
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.
Results Reference
derived

Learn more about this trial

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

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