Study of Neuro-Cognitive Correlates of Pediatric Anxiety Disorders
Overview
- Phase
- Phase 2
- Intervention
- Attention Bias Modification Training
- Conditions
- Anxiety Disorders
- Sponsor
- National Institute of Mental Health (NIMH)
- Enrollment
- 3500
- Locations
- 1
- Primary Endpoint
- Pediatric Anxiety Rating Scale (PARS)
- Status
- Recruiting
- Last Updated
- 8 days ago
Overview
Brief Summary
Study Description:
This study examines relations between neurocognitive and clinical features of pediatric anxiety disorders. The study uses neuro-cognitive tasks, functional magnetic resonance imaging (fMRI), as well as magneto- and electro-encephalography (M/EEG). Patients will be studied over one year, before and after receiving either one of two standard-of-care treatments: cognitive behavioral therapy (CBT) or fluoxetine, a serotonin reuptake inhibitor (SSRI). Healthy comparisons will be studied at comparable time points.
Primary Objectives:
To compare healthy youth and symptomatic, medication-free pediatric patients studied prior to receipt of treatment. The study seeks to detect relations between clinical features of anxiety disorders at baseline and a wide range of neurocognitive features associated with attention, memory, and response to motivational stimuli.
Secondary Objectives:
- To document relations between baseline neurocognitive features and response to Cognitive Behavioral Therapy (CBT) or fluoxetine, as defined by the Pediatric Anxiety Rating Scale (PARS) and Clinical Global Improvement (CGI) Scale.
- To document relations between post-treatment changes in neurocognitive features and anxiety symptoms on the PARS following treatment with Cognitive Behavioral Therapy (CBT) or fluoxetine.
- To document relations among broad arrays of clinical, cognitive, and neural measures
Primary Endpoints:
Indices of percent-signal change in hypothesized brain regions, comprising amygdala, striatum, and prefrontal cortex (PFC) for each fMRI and MEG paradigm.
Secondary Endpoints:
- Treatment-response as defined by a continuous measure, the Pediatric Anxiety Rating Scale score (PARS), and a categorial measure, the Clinical Global Improvement (CGI) score.
- Levels of symptoms and behaviors evoked by tasks that engage attention, memory, and elicit responses to motivational stimuli.
Detailed Description
Study Description: This study examines relations between neurocognitive and clinical features of pediatric anxiety disorders. The study uses neurocognitive tasks, functional magnetic resonance imaging (fMRI), as well as magneto- and electro-encephalography (M/EEG). Patients will be studied over one year, before and after receiving either one of two standard-of-care treatments: cognitive behavioral therapy (CBT) or fluoxetine, a serotonin reuptake inhibitor (SSRI). Healthy comparisons will be studied at comparable time points. Primary Objectives: -To compare healthy youth and symptomatic, medication-free pediatric patients studied prior to receipt of treatment. The study seeks to detect relations between clinical features of anxiety disorders at baseline and a wide range of neurocognitive features associated with attention, memory, and response to motivational stimuli. Secondary Objectives: * To document relations between baseline neurocognitive features and response to Cognitive Behavioral Therapy (CBT) or fluoxetine, as defined by the Pediatric Anxiety Rating Scale (PARS) and Clinical Global Improvement (CGI) Scale. * To document relations between post-treatment changes in neurocognitive features and anxiety symptoms on the PARS following treatment with Cognitive Behavioral Therapy (CBT) or fluoxetine. * To document relations among broad arrays of clinical, cognitive, and neural measures Primary Endpoints: -Indices of percent-signal change in hypothesized brain regions, comprising amygdala, striatum, and prefrontal cortex (PFC) for each fMRI and MEG paradigm. Secondary Endpoints: * Treatment-response as defined by a continuous measure, the Pediatric Anxiety Rating Scale score (PARS), and a categorial measure, the Clinical Global Improvement (CGI) score. * Levels of symptoms and behaviors evoked by tasks that engage attention, memory, and elicit responses to motivational stimuli.
Investigators
Eligibility Criteria
Inclusion Criteria
- •INCLUSION CRITERIA:
- •ALL JUVENILE SUBJECTS
- •Age: 8-17 (subjects who consent as 17-year-olds but turn 18 during the course of the study will be eligible to complete all procedures completed by other subjects who consent as 17-year-olds but do not turn 18).
- •Consent: can give consent/assent (Parents will provide consent; minors will provide assent)
- •IQ: all subjects will have IQ\>70 (Assessment relies on either a WASI or assessment by trained clinical staff during the subject s screening visit. Completion of required activities during the screening visit requires an IQ above 70.)
- •Language: all subjects will speak English (Tasks in this protocol have not been validated in languages other than English)
- •ALL ADULT SUBJECTS
- •Age: 18-65
- •Consent: can give consent
- •IQ: all subjects will have IQ\>70 (Assessment relies on either a WASI or assessment by trained clinical staff during the subject s screening visit. Completion of required activities during the screening visit requires an IQ above 70.)
Exclusion Criteria
- •ALL SUBJECTS
- •Any serious medical condition or condition that interferes with fMRI or M/EEG scanning, and for patients electing medication, any condition that increases risk of SSRI treatment. (All patients will complete a medical history. Healthy volunteer participants will be medication- free and have no current serious medical conditions, based on a review of their medical history. Subjects only will be excluded from the MRI portions of the study based on this exclusion criterion.)
- •Pregnancy (Subjects only will be excluded from the MRI portions of the study based on this exclusion criterion.)
- •Current use of any psychoactive substance; current suicidal ideation; current diagnosis of attention deficit hyperactivity disorder (ADHD) of sufficient severity to require pharmacotherapy. (These factors could complicate treatment with an SSRI. No subject on medication will be accepted into the trial. Subjects will not be taken off of medications to enter the trial.)
- •Current diagnoses, major depressive disorder (MDD), post-traumatic distress disorder, conduct disorder. (These factors may be affected by SSRI treatment, influencing ability to detect effects on anxiety/symptoms of depression. Of note, subjects who present with a diagnosis of MDD will not be eligible for inclusion at the outset of the study. However, youth with anxiety disorders frequently develop MDD when followed over time. Subjects will be allowed to remain in the study if they develop these diagnoses after enrollment.)
- •Past or current history of mania, psychosis, or severe pervasive developmental disorder. (These factors may be affected by SSRI treatment, influencing ability to detect effects on anxiety/symptoms of depression. Of note, subjects who present with a diagnosis of OCD will not be eligible for inclusion at the outset of the study. However, youth with anxiety disorders frequently develop OCD when followed over time. Subjects will be allowed to remain in the study if they develop these diagnoses after enrollment.)
- •Recent use of an SSRI with failure to respond or tolerate SSRI treatment at an adequate dose and duration. (This is designed to exclude subjects who have failed a trial of an SSRI for their current problem with anxiety. For previously enrolled participants, including patients and healthy volunteers, current use of an SSRI does not exclude participation from follow-up research tasks.)
- •History of any (excepting nicotine-related and cannabis-related) DSM5-defined moderate to severe substance use disorder (or DSM-IV-defined substance dependence).
- •HEALTHY ADULT SUBJECTS
- •Any current psychiatric diagnosis (Assessment relies on SCID)
Arms & Interventions
Active
Subjects in both treatment arms receive cognitive behavioral therapy (CBT) for a 12-week period. In the final eight weeks of the trial, the subjects complete either the active-intervention arm or the control invention arm. In these arms, either the active or control treatment is administered immediately before a CBT session.
Intervention: Attention Bias Modification Training
Active
Subjects in both treatment arms receive cognitive behavioral therapy (CBT) for a 12-week period. In the final eight weeks of the trial, the subjects complete either the active-intervention arm or the control invention arm. In these arms, either the active or control treatment is administered immediately before a CBT session.
Intervention: Fluoxetine
Control
Subjects in both treatment arms receive cognitive behavioral therapy (CBT) for a 12-week period. In the final eight weeks of the trial, the subjects complete either the active-intervention arm or the control invention arm. In these arms, either the active or control treatment is administered immediately before a CBT session.
Intervention: Attention Bias Modification Training
Active
Subjects in both treatment arms receive cognitive behavioral therapy (CBT) for a 12-week period. In the final eight weeks of the trial, the subjects complete either the active-intervention arm or the control invention arm. In these arms, either the active or control treatment is administered immediately before a CBT session.
Intervention: Cognitive Behavioral Therapy
Outcomes
Primary Outcomes
Pediatric Anxiety Rating Scale (PARS)
Time Frame: Weekly
Clinician-rated report
Clinical Global Improvement (CGI) Scale
Time Frame: Weekly
Clinician-rated report
Secondary Outcomes
- Another secondary objective is to document relations between post-treatment changes in neurocognitive features and anxiety symptoms on the PARS following treatment with Cognitive Behavioral Therapy (CBT) or fluoxetine.(Changes in symptoms on PARS and changes after 8-12 weeks of treatment in patients)