- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02818751
Neurofunctional Predictors of Escitalopram Treatment Response in Adolescents With Anxiety (FiESTAA)
November 4, 2020 updated by: Jeffrey Strawn, MD, University of Cincinnati
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.
Study Overview
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
Interventional
Enrollment (Actual)
84
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Ohio
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Cincinnati, Ohio, United States, 45219
- University of Cincinnati, Department of Psychiatry & Behavioral Neuroscience
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
12 years to 17 years (Child)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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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.
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Patients being randomized to receive escitalopram.
Other Names:
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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.
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Patients being randomized to receive placebo.
Other Names:
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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).
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Early escitalopram-related functional brain activity changes during emotional processing
Time Frame: From baseline to week 2 of treatment
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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).
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From baseline to week 2 of treatment
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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)
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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.
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from baseline to week 8 (or early termination)
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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)
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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.
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from baseline to week 8 (or early termination)
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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)
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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.
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from baseline to week 8 (or early termination)
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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)
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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)
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from baseline to week 8 (or early termination)
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Jeffrey Strawn, University of Cincinnati
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Strawn JR, Mills JA, Schroeder H, Mossman SA, Varney ST, Ramsey LB, Poweleit EA, Desta Z, Cecil K, DelBello MP. Escitalopram in Adolescents With Generalized Anxiety Disorder: A Double-Blind, Randomized, Placebo-Controlled Study. J Clin Psychiatry. 2020 Aug 25;81(5):20m13396. doi: 10.4088/JCP.20m13396.
- Lu L, Li H, Mills JA, Schroeder H, Mossman SA, Varney ST, Cecil KM, Huang X, Gong Q, Levine A, DelBello MP, Sweeny JA, Strawn JR. Greater Dynamic and Lower Static Functional Brain Connectivity Prospectively Predict Placebo Response in Pediatric Generalized Anxiety Disorder. J Child Adolesc Psychopharmacol. 2020 Dec;30(10):606-616. doi: 10.1089/cap.2020.0024. Epub 2020 Jul 24.
- Lu L, Li H, Baumel WT, Mills JA, Cecil KM, Schroeder HK, Mossman SA, Huang X, Gong Q, Sweeney JA, Strawn JR. Acute neurofunctional effects of escitalopram during emotional processing in pediatric anxiety: a double-blind, placebo-controlled trial. Neuropsychopharmacology. 2022 Apr;47(5):1081-1087. doi: 10.1038/s41386-021-01186-0. Epub 2021 Sep 27.
- Lu L, Mills JA, Li H, Schroeder HK, Mossman SA, Varney ST, Cecil KM, Huang X, Gong Q, Ramsey LB, DelBello MP, Sweeney JA, Strawn JR. Acute Neurofunctional Effects of Escitalopram in Pediatric Anxiety: A Double-Blind, Placebo-Controlled Trial. J Am Acad Child Adolesc Psychiatry. 2021 Oct;60(10):1309-1318. doi: 10.1016/j.jaac.2020.11.023. Epub 2021 Feb 4.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
May 1, 2015
Primary Completion (Actual)
May 1, 2019
Study Completion (Actual)
May 1, 2020
Study Registration Dates
First Submitted
June 2, 2016
First Submitted That Met QC Criteria
June 29, 2016
First Posted (Estimate)
June 30, 2016
Study Record Updates
Last Update Posted (Actual)
November 6, 2020
Last Update Submitted That Met QC Criteria
November 4, 2020
Last Verified
November 1, 2020
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Mental Disorders
- Anxiety Disorders
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Psychotropic Drugs
- Serotonin Uptake Inhibitors
- Neurotransmitter Uptake Inhibitors
- Membrane Transport Modulators
- Serotonin Agents
- Antidepressive Agents
- Antidepressive Agents, Second-Generation
- Citalopram
Other Study ID Numbers
- Strawn FiESTAA
- K23MH106037 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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