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Dimensional Brain Behavior Predictors of CBT Outcomes in Pediatric Anxiety (Anxiety-CBT)

Primary Purpose

Anxiety Disorders, Social Anxiety Disorder, Social Phobia

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Cognitive Behavioral Therapy
Relaxation Therapy
Sponsored by
University of Michigan
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Anxiety Disorders focused on measuring anxiety, social anxiety disorder, generalized anxiety disorder, phobias, fears, worry

Eligibility Criteria

7 Years - 17 Years (Child)All SexesAccepts Healthy Volunteers

Inclusion Criteria for all participants (Clinically Anxious and Healthy):

  • Age 7.0 - 17.99 years
  • Parent or guardian able and willing to give informed consent
  • Ability to tolerate small, enclosed spaces

Exclusion criteria for all participants (Clinically Anxious and Healthy)

  • No metals, implants or metallic substances within or on the body (e.g., orthodontic braces)
  • Vision equal to or better than 20/30 on a Snelling chart, with correction if necessary
  • Not currently taking any psychotropic medication or receiving any psychotherapy (stable doses of stimulants allowable for anxiety subjects with comorbid attention deficit hyperactivity disorder) or receiving hormone therapy other than birth control
  • No lifetime diagnoses of psychotic disorder, mental retardation or autism
  • No history of current substance/alcohol abuse/dependence
  • No evidence of suicidal intentions or behaviors in the past 6 months
  • No history of serious medical or neurological illness
  • If post-pubertal female, not pregnant

Additional Inclusion Criteria for Clinically Anxious Participants:

  • Clinically significant anxiety as determined by structured clinical interview
  • Past history of major depressive episodes are allowable
  • Past history substance/alcohol abuse allowable if in remission for at least 1 year
  • Obsessive-compulsive disorder symptoms are acceptable if not the primary source of interference or distress
  • Anxiety must be primary concern, still bothersome, and CBT for anxiety determined to be appropriate treatment

Additional exclusion criteria for Healthy Participants:

  • No history of past or current mental illness as determined by structured clinical interview

Sites / Locations

  • University of Michigan

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Other

No Intervention

Arm Label

Cognitive Behavioral Therapy

Relaxation Therapy

No Intervention: Healthy youth only

Arm Description

Healthy control participants, matched to gender and age with anxiety patients, will be enrolled. These healthy participants will be scanned with fMRI before and after ~16 weeks, but without any intervention (i.e., no therapy).

Outcomes

Primary Outcome Measures

Brain function/structure as assessed by Magnetic Resonance Imaging scans
Pre- to post-CBT changes in functional, connectivity and structural MRI measures of brain networks relevant for anxiety. Brain regions include the amygdala, anterior insula, dorsal anterior cingulate cortex (dACC) and ventrolateral prefrontal cortex (vlPFC). Functional activation and connectivity of these brain regions are assessed using simple computer tasks performed during MRI scanning. Tasks engage threat reactivity, self-regulatory control and the interaction of these processes. Structural connections between regions will be measured using a MRI technique that measures water diffusion in the brain.

Secondary Outcome Measures

Pediatric Anxiety Rating Scale
The Pediatric Anxiety Rating Scale (PARS) is a clinician-administered assessment to rate the severity of anxiety symptoms associated with common DSM-V anxiety disorders (social phobia, separation anxiety disorder, and generalized anxiety disorder) in children. The investigators are looking for decreases in anxiety severity ratings from pre- to post-treatment.

Full Information

First Posted
June 20, 2016
Last Updated
December 4, 2021
Sponsor
University of Michigan
Collaborators
Ohio State University, National Institute of Mental Health (NIMH)
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1. Study Identification

Unique Protocol Identification Number
NCT02810171
Brief Title
Dimensional Brain Behavior Predictors of CBT Outcomes in Pediatric Anxiety
Acronym
Anxiety-CBT
Official Title
Dimensional Brain Behavior Predictors of CBT Outcomes in Pediatric Anxiety
Study Type
Interventional

2. Study Status

Record Verification Date
July 2021
Overall Recruitment Status
Completed
Study Start Date
December 2016 (Actual)
Primary Completion Date
July 2021 (Actual)
Study Completion Date
November 12, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Michigan
Collaborators
Ohio State University, National Institute of Mental Health (NIMH)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Anxiety is among the most prevalent, costly and disabling illnesses and tends emerge early in childhood. Cognitive behavioral therapy (CBT) is the first-line treatment for early life anxiety, but as many as 40% of young patients who receive CBT fail to get better. The proposed study will examine brain changes marking positive response to CBT for anxiety and how these changes may differ in children compared adolescents. By helping us to understand how CBT works, this study will pave the way for new treatments to stop anxiety early.
Detailed Description
Impairing anxiety affects 33% of the population by adolescence and can become chronic, leading to depression, substance abuse, school-drop out and even suicide. To reduce anxiety and prevent its sequelae, patients must be effectively treated early; yet, the first line intervention, cognitive behavioral therapy (CBT), has a heterogeneous response with 40-60% of treated patients continuing to experience impairment from residual symptoms. The reasons for variability in CBT outcomes remain poorly understood, but individual (including developmental) differences in brain-behavioral targets of CBT may contribute. This proposal addresses two primary questions: 1) Do individual differences in CBT-relevant brain-behavioral functions lead to variation in CBT outcomes? and 2) Does development contribute to this variation? To answer these questions, this study will measure changes in brain and behavior markers of anxiety, before and after CBT, in children and adolescents across traditional, categorical anxiety disorders (e.g., social, generalized and separation anxiety disorders). Given that CBT facilitates control over fear to enable effective regulation, the investigators hypothesize that brain-behavioral markers of fear sensitivity, cognitive regulatory capacity and cognitive regulation of fear will predict and characterize mechanisms of CBT effect. In addition, the investigators hypothesize that these markers will differentially relate to CBT effect, depending on patient age. Children and adolescents (7.0 - 17.99 years) with clinically impairing anxiety will be randomized to receive CBT or a relaxation control therapy for 12 weeks. Before and after therapy, all participants will receive an MRI scan to see what regions of the brain become active when emotion and concentration tasks are performed and how that activation is changed after CBT. While the study itself is of parallel design for its data-collection and measurement purpose, it is listed as a partial-crossover design in the IRB-approved protocol because subjects randomized to the relaxation therapy are given the option of receiving 12-weeks of CBT sessions after the relaxation therapy data has been collected. Some limited data will be collected in patients who are initially randomized to relaxation therapy but then opt to crossover to CBT. MRI data will also be collected in healthy youth before and after 12 weeks (but without intervening therapy) to allow the investigators to control for the simple effects of time that may cause brain changes that are not related to therapy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anxiety Disorders, Social Anxiety Disorder, Social Phobia, Generalized Anxiety Disorder, Separation Anxiety Disorder, Specific Phobia, Phobia, Agoraphobia, Panic Disorder, Panic Attack, Anxiety
Keywords
anxiety, social anxiety disorder, generalized anxiety disorder, phobias, fears, worry

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
InvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
207 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cognitive Behavioral Therapy
Arm Type
Active Comparator
Arm Title
Relaxation Therapy
Arm Type
Other
Arm Title
No Intervention: Healthy youth only
Arm Type
No Intervention
Arm Description
Healthy control participants, matched to gender and age with anxiety patients, will be enrolled. These healthy participants will be scanned with fMRI before and after ~16 weeks, but without any intervention (i.e., no therapy).
Intervention Type
Behavioral
Intervention Name(s)
Cognitive Behavioral Therapy
Other Intervention Name(s)
CBT
Intervention Description
A therapy which teaches patients coping skills to manage anxiety and gradually yet repeatedly exposes patients to anxiety-provoking thoughts and situations until the anxiety habituates/diminishes.
Intervention Type
Behavioral
Intervention Name(s)
Relaxation Therapy
Intervention Description
An active control therapy with minimal effects on anxiety symptoms. If randomized to this therapy, participants will have the option to cross-over to CBT once the relaxation therapy arms has been completed.
Primary Outcome Measure Information:
Title
Brain function/structure as assessed by Magnetic Resonance Imaging scans
Description
Pre- to post-CBT changes in functional, connectivity and structural MRI measures of brain networks relevant for anxiety. Brain regions include the amygdala, anterior insula, dorsal anterior cingulate cortex (dACC) and ventrolateral prefrontal cortex (vlPFC). Functional activation and connectivity of these brain regions are assessed using simple computer tasks performed during MRI scanning. Tasks engage threat reactivity, self-regulatory control and the interaction of these processes. Structural connections between regions will be measured using a MRI technique that measures water diffusion in the brain.
Time Frame
Baseline and 12-weeks
Secondary Outcome Measure Information:
Title
Pediatric Anxiety Rating Scale
Description
The Pediatric Anxiety Rating Scale (PARS) is a clinician-administered assessment to rate the severity of anxiety symptoms associated with common DSM-V anxiety disorders (social phobia, separation anxiety disorder, and generalized anxiety disorder) in children. The investigators are looking for decreases in anxiety severity ratings from pre- to post-treatment.
Time Frame
weeks 0, 3, 6, 9, 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
7 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria for all participants (Clinically Anxious and Healthy): Age 7.0 - 17.99 years Parent or guardian able and willing to give informed consent Ability to tolerate small, enclosed spaces Exclusion criteria for all participants (Clinically Anxious and Healthy) No metals, implants or metallic substances within or on the body (e.g., orthodontic braces) Vision equal to or better than 20/30 on a Snelling chart, with correction if necessary Not currently taking any psychotropic medication or receiving any psychotherapy (stable doses of stimulants allowable for anxiety subjects with comorbid attention deficit hyperactivity disorder) or receiving hormone therapy other than birth control No lifetime diagnoses of psychotic disorder, mental retardation or autism No history of current substance/alcohol abuse/dependence No evidence of suicidal intentions or behaviors in the past 6 months No history of serious medical or neurological illness If post-pubertal female, not pregnant Additional Inclusion Criteria for Clinically Anxious Participants: Clinically significant anxiety as determined by structured clinical interview Past history of major depressive episodes are allowable Past history substance/alcohol abuse allowable if in remission for at least 1 year Obsessive-compulsive disorder symptoms are acceptable if not the primary source of interference or distress Anxiety must be primary concern, still bothersome, and CBT for anxiety determined to be appropriate treatment Additional exclusion criteria for Healthy Participants: No history of past or current mental illness as determined by structured clinical interview
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kate D. Fitzgerald, M.D.
Organizational Affiliation
University of Michigan
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Anonymized data will be shared with the National Database for Autism Research (NDAR) and the Research Domain Criteria Database (RDoCdb).
Citations:
PubMed Identifier
34966981
Citation
Rueppel M, Mannella KA, Fitzgerald KD, Schroder HS. Post-error slowing in anxiety and obsessive-compulsive disorders. Cogn Affect Behav Neurosci. 2022 Jun;22(3):610-624. doi: 10.3758/s13415-021-00976-9. Epub 2021 Dec 29.
Results Reference
derived

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Dimensional Brain Behavior Predictors of CBT Outcomes in Pediatric Anxiety

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