Acute and Long-Term Antidepressant Treatment Success in Adolescents With Anxiety (AtLAS-A) (AtLAS-A)

Acute, Double-blind, Adaptively Randomized Treatment With Duloxetine or Escitalopram, Followed by Open-label Naturalistic Follow-up.

Acute, double-blind, adaptively randomized treatment with duloxetine or escitalopram, followed by open-label naturalistic follow-up.

Study Overview

• Status: Recruiting
• Conditions: Anxiety; Depressive Symptoms
• Intervention / Treatment: Drug: Duloxetine; Drug: Escitalopram

Detailed Description

To identify predictors of the magnitude and trajectory of response to flexibly-dosed duloxetine and escitalopram response in adolescents with anxiety, including those with depressive symptoms. And also to examine long-term predictors of sustained response and relapse in adolescents. To examine predictors of developing depressive disorders in anxious adolescents.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Heidi K Schroeder, BS; Phone Number: 513-558-4422; Email: heysehk@uc.edu
• Study Contact Backup: Name: Jeffrey R Strawn, MD; Phone Number: 513-558-4315; Email: strawnjr@uc.edu

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Recruiting
      • University of Cincinnati
      • Contact: Jeffrey R Strawn, MD; Phone Number: 513-558-7700; Email: strawnjr@uc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 13 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Written, informed assent and consent.
• Patients, parent/guardian/LAR must be fluent in the English.
• 12 to 17 years of age, inclusive, at Screening.
• Patients must meet DSM-512 criteria for generalized, social and/or separation anxiety disorder and/or panic disorder, 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's condition, oversee the administration of the investigational product.
• No clinically significant abnormalities on physical examination.
• Negative pregnancy test at Screening in females.
• Negative urine drug screen at Screening.

• Sexually active patients must practice a reliable method of contraception (Section 15.0) 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. estrogren-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:

• DSM-512 diagnosis other than generalized anxiety, social anxiety, separation anxiety or panic disorder(s) that is the primary focus of treatment.
• A history of intellectual disability.
• 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.
• Allergy, intolerance, non-response or hypersensitivity to escitalopram or duloxetine.
• Subjects taking other medications that require a taper or washout of more than 5 days.
• Patients who have initiated/terminated psychotherapy/behavior therapy within 1 month before Visit 2 (Baseline), or who plan to initiate/change said therapies during the course of the study will be excluded; if the patient is engaged in psychotherapy, it must have been stable for 1 month prior to baseline.
• A clinically-significant medical illness.
• QTc >450 in males / >460 in females (prolonged QTc based on American Heart Association recommendations for Standardization and Interpretation of the EKG81
• Alcohol or substance use disorder within the past 6 months (nicotine use is permitted).
• Positive urine pregnancy test/pregnancy or breast feeding.
• A positive urine drug screen.
• Patients who are unable to swallow capsules.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Duloxetine; Patients randomized to duloxetine, treatment will be initiated at 30 mg qAM through Week 4 (V5) (consistent with the registration trial for duloxetine in pediatric patients with generalized anxiety disorder). Then, duloxetine will be increased to 60 mg qAM at Week 4 (V5) and will be continued at this dose until Week 6 (V6) or the end of the acute phase of the study. Beginning at Week 6 (V6), duloxetine may be increased to 90 mg daily and at Week 8 (V7), may be increased to 120 mg daily.	Drug: Duloxetine; Encapsulated duloxetine 30 mg, 60 mg; once-daily; Other Names: Cymbalta; Irenka
Active Comparator: Escitalopram; Patients randomized to escitalopram, will initiate treatment at 5 mg qAM for 1 week and then 10 mg qAM (the recommended starting dose for adolescents 12-17 years and the dose used in the pediatric registration trials). After Week 4 (V5), escitalopram will be increased to 15 mg and this dose will be continued until either Week 6 (V6) or the end of the acute phase of the study; however, at Week 6 (V6), escitalopram may be increased to 20 mg qAM based on efficacy.	Drug: Escitalopram; Encapsulated escitalopram 5 mg, 10 mg, 15 mg, 20 mg; once-daily; Other Names: Lexapro

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 24 months (Early Term)
Change from Baseline in the Clinical Global Impression of Severity (CGI-S)	CGI-S is a seven point scale where 1=Normal and 7=Among the most extremely ill patients.	Baseline to Week 10 (Early Term)

Collaborators and Investigators

• Sponsor: University of Cincinnati
• Investigators: Principal Investigator: Jeffrey R Strawn, MD, University of Cincinnati

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2020
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): August 1, 2025

Study Registration Dates

• First Submitted: January 7, 2020
• First Submitted That Met QC Criteria: January 27, 2020
• First Posted (Actual): January 29, 2020

Study Record Updates

• Last Update Posted (Actual): August 29, 2024
• Last Update Submitted That Met QC Criteria: August 28, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Depression; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Dopamine Agents; Serotonin and Noradrenaline Reuptake Inhibitors; Selective Serotonin Reuptake Inhibitors; Duloxetine Hydrochloride; Escitalopram
• Other Study ID Numbers: Strawn AtLAS-A

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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