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

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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

Tracking Information
First Submitted Date  ICMJE June 2, 2016
First Posted Date  ICMJE June 30, 2016
Last Update Posted Date November 6, 2020
Actual Study Start Date  ICMJE May 2015
Actual Primary Completion Date May 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 29, 2016)
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).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 23, 2018)
  • 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.
  • 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.
  • 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.
  • 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)
Original Secondary Outcome Measures  ICMJE
 (submitted: June 29, 2016)
  • Baseline functional activity in the ventrolateral prefrontal cortex and treatment response (at week 8/early termination) [ Time Frame: from baseline to week 8 (or early termination) ]
    o determine if baseline functional activity in the ventrolateral prefrontal cortex predicts a Clinical Global Impression-Improvement score </= 2 at week 8/early termination.
  • Change in functional activity in the ventrolateral prefrontal cortex (from baseline to week 2) and treatment response (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 a Clinical Global Impression-Improvement score </= 2 at week 8/early termination.
  • 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.
  • Baseline functional connectivity between the ventrolateral prefrontal cortex and the amygdala and treatment response at week 8/early termination. [ Time Frame: from baseline to week 8 (or early termination) ]
    To determine if baseline functional connectivity between the ventrolateral prefrontal cortex and the amygdala predicts a Clinical Global Impression-Improvement score </= to 2 at week 8/early termination.
  • Change in functional connectivity between the ventrolateral prefrontal cortex and the amygdala (from baseline to week 2) and treatment response 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 a Clinical Global Impression-Improvement score </= to 2 at week 8/ early termination.
  • 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.
  • Baseline glutamate and γ-aminobutyric acid concentrations in the anterior cingulate cortex predict a Clinical Global Impression-Improvement score </= to 2 at week 8/early termination. [ Time Frame: from baseline to week 8 (or early termination) ]
    To determine if baseline glutamate concentrations in the anterior cingulate cortex predict a Clinical Global Impression-Improvement score </= to 2 at week 8/early termination.
  • Baseline γ-aminobutyric acid concentrations in the anterior cingulate cortex predict a Clinical Global Impression-Improvement score </= to 2 at week 8/early termination. [ Time Frame: from baseline to week 8 (or early termination) ]
    To determine if baseline γ-aminobutyric acid concentrations in the anterior cingulate cortex predict a Clinical Global Impression-Improvement score </= to 2 at week 8/early termination.
  • Change in γ-aminobutyric acid concentrations in the anterior cingulate cortex (from baseline to week 2) predict a Clinical Global Impression-Improvement score </= to 2 at week 8/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 cortex (from baseline to week 2) predict a Clinical Global Impression-Improvement score </= to 2 at week 8/early termination.
  • Change in γ-aminobutyric acid 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 γ-aminobutyric acid concentrations in the anterior cingulate cortex predict improvement in Pediatric Anxiety Rating Scale score from baseline to week 8/early termination.
  • 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)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Neurofunctional Predictors of Escitalopram Treatment Response in Adolescents With Anxiety
Official Title  ICMJE Neurofunctional Predictors of Escitalopram Treatment Response in Adolescents With Anxiety
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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Anxiety
Intervention  ICMJE
  • Drug: Escitalopram
    Patients being randomized to receive escitalopram.
    Other Name: Lexapro
  • Other: Placebo
    Patients being randomized to receive placebo.
    Other Name: Sugar Pill
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Escitalopram
  • 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.
    Intervention: Other: Placebo
  • 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).
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 29, 2016)
84
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE May 2020
Actual Primary Completion Date May 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02818751
Other Study ID Numbers  ICMJE Strawn FiESTAA
K23MH106037 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Jeffrey Strawn, MD, University of Cincinnati
Study Sponsor  ICMJE University of Cincinnati
Collaborators  ICMJE National Institute of Mental Health (NIMH)
Investigators  ICMJE
Principal Investigator: Jeffrey Strawn University of Cincinnati
PRS Account University of Cincinnati
Verification Date November 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP