Anxiety DisordersAnxiety-CBTNCT02810171
Dimensional Brain Behavior Predictors of CBT Outcomes in Pediatric Anxiety
A study testing Cognitive Behavioral Therapy and Relaxation Therapy in people with Anxiety Disorders and Social Anxiety Disorder, run by University of Michigan at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 7 to 17 yearsHealthy volunteers can take part
- Conditions the study is for
- Anxiety Disorders, Social Anxiety Disorder, Social Phobia
- What is being tested?
- Cognitive Behavioral Therapy and Relaxation Therapy
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 207 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2016to 12 Nov 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 7 to 17 years
- All sexes
- Healthy volunteers accepted
- Child
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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Conditions
- Anxiety Disorders, Social Anxiety Disorder, Social Phobia, Generalized Anxiety Disorder, Separation Anxiety Disorder, Specific Phobia
- Being tested
- Cognitive Behavioral Therapy, Relaxation Therapy
- Keywords
- anxiety, social anxiety disorder, generalized anxiety disorder, phobias, fears, worry
- Medical subject headings
- Anxiety Disorders, Phobia, Social, Generalized Anxiety Disorder, Anxiety, Separation, Phobia, Specific, Phobic Disorders, Agoraphobia, Panic Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cognitive Behavioral TherapyBehavioural
Also called CBT
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.
Relaxation TherapyBehavioural
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.
| Study group | Role | What they receive |
|---|---|---|
| Cognitive Behavioral Therapy | Active comparator | Not described Receives: Behavioral: Cognitive Behavioral Therapy |
| Relaxation Therapy | Other | Not described Receives: Behavioral: Relaxation Therapy |
| No Intervention: Healthy youth only | No intervention | 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). |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and 12-weeks
Secondary outcomes (1)
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.
Measured: weeks 0, 3, 6, 9, 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2016 (estimated)
- Study startDec 2016
- Primary completionJul 2021
- Study completion12 Nov 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Anxiety DisordersStudies of the same condition, open and under way.
- More trials run by University of MichiganThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 207 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Christopher Monk, University of Michigan
- Investigators
- Kate D. Fitzgerald, M.D., Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02810171
- Sponsor's protocol ID
- HUM00118950
- Other IDs
- R01MH107419
- Acronym
- Anxiety-CBT
- Status last verified
- Jul 2021
- First submitted
- 20 Jun 2016
- Last updated
- 20 Dec 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Anonymized data will be shared with the National Database for Autism Research (NDAR) and the Research Domain Criteria Database (RDoCdb).
Publications
Bilek EL, Iturra-Mena AM, Becker HC, Phan KL, Monk CS, Fitzgerald KD. Exposure-Focused Cognitive-Behavioral Therapy for Youth Anxiety Disorders: Superiority Over Relaxation-Based Comparator and Predictors of Response. JAACAP Open. 2025 Apr 25;3(4):1161-1176. doi: 10.1016/j.jaacop.2025.04.003. eCollection 2025 Dec.
PubMed 41367992Diaz DE, Russman Block SR, Becker HC, Phan KL, Monk CS, Fitzgerald KD. Neural Substrates of Emotion Processing and Cognitive Control Over Emotion in Youth Anxiety: An RDoC-Informed Study Across the Clinical to Nonclinical Continuum of Severity. J Am Acad Child Adolesc Psychiatry. 2025 Apr;64(4):488-498. doi: 10.1016/j.jaac.2024.06.010. Epub 2024 Jul 24.
PubMed 39059719Rueppel 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.
PubMed 34966981
Study at a glance
From the registry record, last updated by the sponsor on 20 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dimensional Brain Behavior Predictors of CBT Outcomes in Pediatric Anxiety
- ClinicalTrials.gov ID
- NCT02810171
- Acronym / sponsor ID
- Anxiety-CBT / HUM00118950
- Conditions
- Anxiety Disorders, Social Anxiety Disorder, Social Phobia, Generalized Anxiety Disorder, Separation Anxiety Disorder, Specific Phobia
- Keywords
- anxiety, social anxiety disorder, generalized anxiety disorder, phobias, fears, worry
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 207 participants (actual)
- Lead sponsor
- University of MichiganUniversity, hospital or other
- Collaborators
- Ohio State University, National Institute of Mental Health (NIMH)
- Study start
- Dec 2016 (actual)
- Primary completion
- Jul 2021 (actual)
- Study completion
- 12 Nov 2021 (actual)
- First posted
- 22 Jun 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cognitive Behavioral Therapy | Active comparator | Behavioral: Cognitive Behavioral Therapy |
| Relaxation Therapy | Other | Behavioral: Relaxation Therapy |
| No Intervention: Healthy youth only | No intervention | –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). |
Who may qualify
- Ages
- 7 to 17 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cognitive Behavioral TherapyAlso: CBTA 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. | Behavioural | Cognitive Behavioral Therapy |
| Relaxation TherapyAn 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. | Behavioural | Relaxation Therapy |
Primary outcome
Brain function/structure as assessed by Magnetic Resonance Imaging scans
Time frame: Baseline and 12-weeks
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.
1 secondary outcome
Pediatric Anxiety Rating Scale
Time frame: weeks 0, 3, 6, 9, 12
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Dec 2021.
- Derived from this study: PubMed 41367992Bilek EL, Iturra-Mena AM, Becker HC, Phan KL, Monk CS, Fitzgerald KD. Exposure-Focused Cognitive-Behavioral Therapy for Youth Anxiety Disorders: Superiority Over Relaxation-Based Comparator and Predictors of Response. JAACAP Open. 2025 Apr 25;3(4):1161-1176. doi: 10.1016/j.jaacop.2025.04.003. eCollection 2025 Dec.
- Derived from this study: PubMed 39059719Diaz DE, Russman Block SR, Becker HC, Phan KL, Monk CS, Fitzgerald KD. Neural Substrates of Emotion Processing and Cognitive Control Over Emotion in Youth Anxiety: An RDoC-Informed Study Across the Clinical to Nonclinical Continuum of Severity. J Am Acad Child Adolesc Psychiatry. 2025 Apr;64(4):488-498. doi: 10.1016/j.jaac.2024.06.010. Epub 2024 Jul 24.
- Derived from this study: PubMed 34966981Rueppel 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.
- Individual participant dataSharing planned: Yes. Anonymized data will be shared with the National Database for Autism Research (NDAR) and the Research Domain Criteria Database (RDoCdb).
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kate D. Fitzgerald, M.D. principal investigator
University of Michigan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cognitive Behavioral Therapy and Relaxation Therapy in people with Anxiety Disorders and Social Anxiety Disorder, run by University of Michigan at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Brain function/structure as assessed by Magnetic Resonance Imaging scans (time frame: Baseline and 12-weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02810171, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Dec 2021.