Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Neurofunctional Predictors of Escitalopram Treatment Response in Adolescents With Anxiety (FiESTAA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02818751
Recruitment Status : Completed
First Posted : June 30, 2016
Last Update Posted : November 6, 2020
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Jeffrey Strawn, MD, University of Cincinnati

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
Neurofunctional Predictors of Escitalopram Treatment Response in Adolescents with Anxiety. To determine the effects of escitalopram on functional activation patterns during a Continuous Performance Task with Emotional and Neutral Distracters, the CPT-END. To examine baseline functional activity and functional connectivity profiles in the ventrolateral prefrontal cortex as markers of subsequent treatment response to escitalopram in adolescents with generalized anxiety disorder (GAD). To use proton magnetic resonance spectroscopy (1H MRS) to examine glutamatergic and γ-aminobutyric acid (GABA)-related abnormalities in the anterior cingulate in adolescents with GAD as compared to healthy adolescents.

Condition or disease Intervention/treatment Phase
Anxiety Drug: Escitalopram Other: Placebo Not Applicable

Detailed Description:
The long-term goal of this study is to explore the neurobiological basis of generalized anxiety disorder (GAD) using a validated functional MRI (fMRI) paradigm and functional connectivity analyses with a cohort of GAD patients and healthy subjects and generating feasibility and preliminary data regarding treatment-related effects of escitalopram on brain functional activation and Fc patterns in pediatric GAD. An additional goal is to identify biological markers in saliva and urine that will predict treatment response in pediatric subjects with GAD. The central hypothesis of this proposal is that core dysfunction within the prefrontal-amygdala network, which the investigators and others have observed in GAD, will be normalized by successful treatment. The rationale underlying this hypothesis is that, despite the high prevalence of GAD, there is a need to understand its neurobiology and to identify biomarkers of treatment response and the mechanisms by which selective serotonin reuptake inhibitors (SSRIs) putatively effect changes in the neurocircuitry of pediatric GAD.
Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 84 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Neurofunctional Predictors of Escitalopram Treatment Response in Adolescents With Anxiety
Actual Study Start Date : May 2015
Actual Primary Completion Date : May 2019
Actual Study Completion Date : May 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Anxiety

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: Escitalopram
Patients being randomized to receive escitalopram, at an initial dose of 5 mg (oral) daily for 2 days. On day 3, escitalopram will be increased to 10 mg daily and continued for 7 days. Then, on day 10, escitalopram will be increased to 15 mg. At the week 4 visit, the dose of escitalopram may be increased to 20 mg, based on the investigator's clinical judgment and if significant anxiety symptoms are still present.
 Drug: Escitalopram
Patients being randomized to receive escitalopram.
Other Name: Lexapro
Placebo Comparator: Placebo
Patients will receive placebo (sugar pill) at an initial dose of 5 mg daily for 2 days. On day 3, placebo will be increased to 10 mg daily and continued for 7 days to match the experimental group.
 Other: Placebo
Patients being randomized to receive placebo.
Other Name: Sugar Pill
No Intervention: Healthy Controls
Healthy adolescents will receive fMRI scans at the same time points, which will provide assessments of the stability of neurophysiologic measures and will be used to adjust and interpret comparisons within the patients (i.e., whether patient values are changing toward or away from those of healthy adolescents).


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Early escitalopram-related functional brain activity changes during emotional processing [ Time Frame: From baseline to week 2 of treatment ]
    To determine if escitalopram treatment (over a 2 week period) increases functional brain activation during the processing of emotional images while performing a continuous processing task with emotional and neutral distracters (CPT-END) (also over a 2 week period).


Secondary Outcome Measures :
  1. Change in functional activity in the ventrolateral prefrontal cortex (from baseline to week 2) and improvement in Pediatric Anxiety Rating Scale score (at week 8/early termination) [ Time Frame: from baseline to week 8 (or early termination) ]
    To determine if the change in functional activity in the ventrolateral prefrontal cortex (from baseline to week 2) predicts improvement in Pediatric Anxiety Rating Scale score from baseline to week 8/early termination.

  2. Change in functional connectivity between the ventrolateral prefrontal cortex and the amygdala (from baseline to week 2) and improvement in Pediatric Anxiety Rating Scale score (at week 8/early termination) [ Time Frame: from baseline to week 8 (or early termination) ]
    To determine if the change in functional connectivity between the ventrolateral prefrontal cortex and the amygdala (from baseline to week 2) predicts improvement in Pediatric Anxiety Rating Scale score from baseline to week 8/early termination.

  3. Change in glutamate concentrations in the anterior cingulate cortex predict improvement in Pediatric Anxiety Rating Scale score from baseline to week 8/early termination. [ Time Frame: from baseline to week 8 (or early termination) ]
    To determine if change in glutamate concentrations in the anterior cingulate cortex predict improvement in Pediatric Anxiety Rating Scale score from baseline to week 8/early termination.

  4. Change in γ-aminobutyric acid concentrations in the anterior cingulate (from baseline to week 2) predicts improvement in Pediatric Anxiety Rating Scale score from baseline to week 8 (or early termination) [ Time Frame: from baseline to week 8 (or early termination) ]
    To determine if the change in γ-aminobutyric acid concentrations in the anterior cingulate (from baseline to week 2) predicts improvement in Pediatric Anxiety Rating Scale score from baseline to week 8 (or early termination)


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   12 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Inclusion - Anxiety Subjects:

  • Diagnostic and Statistical Manual-IV (Text Revision) criteria for generalized anxiety disorder diagnosed by the Anxiety Disorders Interview Schedule (ADIS-IV)
  • Baseline Pediatric Anxiety Rating Scale (PARS) score ≥15 at baseline
  • Ages 12-17 years 11 months old
  • Fluent in English
  • Provision of written informed consent by a legal guardian and written assent by the subject
  • Tanner scale stages II-V, in order to include only post-pubescent subjects and minimize brain changes associated with the onset of puberty
  • Does not have a history of intolerance, non-response or hypersensitivity to escitalopram
  • No co-occurring Diagnostic and Statistical Manual-IV (Text Revision) diagnosis mood (except dysthymia, depression not otherwise specified), eating, pervasive developmental disorder or psychotic disorders
  • Subjects will be excluded if there are any lifetime diagnosis of mental retardation (intelligence quotient < 70)
  • Subjects with any history of alcohol or drug dependence or any alcohol abuse within the past 6 months (nicotine dependence is permitted) will be excluded
  • No new psychotherapy will be permitted during study participation and if the patient is engaged in psychotherapy, it must have been stable for 1 month prior to baseline
  • Females will not be eligible to participate if pregnant, breast feeding or lactating.

Inclusion - Healthy Subjects:

  • Ages of 12-17 years and 11 months
  • No history of any Diagnostic and Statistical Manual-IV (Text Revision) Axis I disorders (nicotine dependence is permitted)
  • No first-degree relatives with an affective or psychotic disorder
  • No medications with central nervous system effects within 5 half-lives
  • Fluent in English
  • Tanner stage II-V
  • Provision of informed consent and assent.

Exclusion Criteria:

Exclusion - Generalized Anxiety Disorder Patients & Healthy Subjects:

  • Contraindication to an magnetic resonance imaging (MRI) scan (e.g., braces or claustrophobia)
  • An unstable medical or neurological illness that could influence fMRI or magnetic resonance spectroscopy results
  • Subjects will be excluded if there are any lifetime diagnosis of mental retardation or intelligence quotient < 70)
  • A positive pregnancy test
  • Adolescents will be excluded for treatment with a medication with central nervous system effects that requires more than 5 days of a screening period in order to minimize the length of time between screening and baseline and maximize patient safety, while recognizing that a longer taper period is required of some medications
  • Adolescents with any history of major medical or neurological disorders that may result in neurofunctional or neurochemical abnormalities including loss of consciousness for >10 minutes will be excluded
  • No co-occurring Diagnostic and Statistical Manual-IV (Text Revision) diagnosis mood (other than dysthymia or Depression Not Otherwise Specified), eating, pervasive developmental disorder or psychotic disorders
  • Subjects will be excluded if there are any lifetime diagnosis of mental retardation or intelligence quotient < 70
  • Subjects with any history of alcohol or drug dependence or any alcohol abuse within the past 6 months (nicotine dependence is permitted) will be excluded
  • No new psychotherapy will be permitted during study participation and if the patient is engaged in psychotherapy, it must have been stable for 1 month prior to baseline
  • Females will not be eligible to participate if pregnant, breast feeding or lactating
  • The patient lives >100 miles from the University of Cincinnati or is not able to attend follow-up visits
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02818751


Locations
Layout table for location information
United States, Ohio
University of Cincinnati, Department of Psychiatry & Behavioral Neuroscience
Cincinnati, Ohio, United States, 45219
Sponsors and Collaborators
University of Cincinnati
National Institute of Mental Health (NIMH)
Investigators
Layout table for investigator information
Principal Investigator: Jeffrey Strawn University of Cincinnati
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Publications of Results:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Layout table for additonal information
Responsible Party: Jeffrey Strawn, MD, Associate Professor of Psychiatry, University of Cincinnati
ClinicalTrials.gov Identifier: NCT02818751    
Other Study ID Numbers: Strawn FiESTAA
K23MH106037 ( U.S. NIH Grant/Contract )
First Posted: June 30, 2016    Key Record Dates
Last Update Posted: November 6, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Jeffrey Strawn, MD, University of Cincinnati:
Anxiety
Adolescents with Anxiety
Additional relevant MeSH terms:
Layout table for MeSH terms
Anxiety Disorders
Mental Disorders
Citalopram
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
 Neurotransmitter Agents
Serotonin Agents
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs