Study of Neuro-Cognitive Correlates of Pediatric Anxiety Disorders

Major Depressive Disorder Clinical Trial

Official title:

Study of Neuro-Cognitive Correlates of Pediatric Anxiety Disorders

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00018057
• Other study ID #: 010192
• Secondary ID: 01-M-0192
• Status: Recruiting
• Phase: Phase 2
• Start date: October 2, 2001
• Est. completion date: January 1, 2029

Study information

• Verified date: March 22, 2024
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Daniel S Pine, M.D.
• Phone: (301) 594-1318
• Email: daniel.pine[@]nih.gov
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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:

1. 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.

2. 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.

3. 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:

1. 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.

2. Levels of symptoms and behaviors evoked by tasks that engage attention, memory, and elicit responses to motivational stimuli.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2530
• Est. completion date: January 1, 2029
• Est. primary completion date: January 1, 2029
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 8 Years to 65 Years

Eligibility

• 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.)

• Language: all subjects will speak English (Tasks in this protocol have not been validated in languages other than English)

ALL SUBJECTS WITH AN ANXIETY DISORDER

• Diagnosis: Current Diagnosis of Social Phobia, Separation Anxiety, Generalized Anxiety Disorder, or Panic Disorder (Based on K-SADS (juveniles) or SCID (adults))

• Symptom Severity: Clinically significant, ongoing anxiety symptoms (This will be documented by clinician review with patients and their families during at least two visits with families.)

• Clinical Impairment: Clinically significant, ongoing distress or impairment from anxiety (This will be documented by clinician review with patients and their families during at least two visits with families.)

ALL PREVIOUSLY ENROLLED ADOLESCENT PATIENTS, CHILD AND ADULT HEALTHY VOLUNTEERS, AND ALL HEALTHY VOLUNTEERS TURNED PATIENTS

• Diagnosis: Current Diagnosis of Social Phobia, Separation Anxiety, Generalized Anxiety Disorder, or Panic Disorder; No current diagnosis (Based on K-SADS (juveniles) or SCID (adults))

• Clinical Impairment (as applicable): Clinically significant, ongoing symptoms (This will be documented by clinician review with patients and their families during at least two visits with families.)

• Symptom Severity (as applicable): Clinically significant, ongoing symptoms (This will be documented by clinician review with patients and their families during at least two visits with families.)

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 Tourette s Disorder, major depressive disorder (MDD); obsessive compulsive disorder (OCD), 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 or OCD will not be eligible for inclusion at the outset of the study. However, youth with anxiety disorders frequently develop OCD and 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 MDD or OCD will not be eligible for inclusion at the outset of the study. However, youth with anxiety disorders frequently develop OCD and MDD 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.)

• NIMH employees and staff and their immediate family members will be excluded from the study per NIMH policy.

• 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)

Related Conditions & MeSH terms

• Anxiety Disorders
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Intervention

Behavioral:
• Attention Bias Modification Training
The intervention is computer-based. The active and control treatments have two components. In one component of the active intervention, subjects are asked to indicate the identity of a letter that appears behind a neutral face, opposite from an angry face. In another component of the active intervention, subjects are asked to identify numbers that are hidden within a puzzle, in locations distal from angry faces. In both components of the active intervention, subjects implicitly learn to shift their attention away from angry faces. This is because the faces are systematically arranged to be far removed from letters and numbers that need to be identified. The control arm of the intervention involves similar components. However, unlike in the intervention arm, angry faces appear in various locations near letters and numbers. Therefore, attention is not shaped in the control arm. This intervention requires five minutes per session and is administered before weekly psychotherapy sessions.

Drug:
• Fluoxetine
Randomized assignment.

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center	Bethesda	Maryland

Sponsors (4)

Lead Sponsor	Collaborator
National Institute of Mental Health (NIMH)	University of Maryland, University of Minnesota, University of Oregon

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pediatric Anxiety Rating Scale (PARS)	Clinician-rated report	Weekly
Primary	Clinical Global Improvement (CGI) Scale	Clinician-rated report	Weekly

External Links

•   NIH Clinical Center Detailed Web Page