Negative Valence Brain Targets and Predictors of Anxiety and Depression Treatment
Primary Purpose
Internalizing Psychopathologies (IPs) Depression and Anxiety
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
SSRI
CBT
Sponsored by
About this trial
This is an interventional treatment trial for Internalizing Psychopathologies (IPs) Depression and Anxiety focused on measuring Internalizing psychopathologies, Depression, Anxiety, MRI, medication treatment, psychotherapy, brain function
Eligibility Criteria
Inclusion Criteria:
- Generally medically and neurologically healthy
- Chief complaint(s) of "anxiety, worry, and/or depressed mood
Exclusion Criteria:
- Current or past manic/hypomanic episode or psychotic symptoms
- Suicidal ideation
- Presence of contraindications (e.g., history of SSRI adverse events) or prior history of SSRI resistance (no response to > 2 SSRI trials with adequate duration and dose)
- Obsessive compulsive disorder (OCD)
- Current cognitive dysfunction (traumatic brain injury, mental retardation, dementia)
- Current alcohol and substance dependence
- Ongoing therapy/medication treatment of any kind outside of this study
Sites / Locations
- University of Illinois at Chicago
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
SSRI
CBT
Arm Description
sertraline: 100-200mg, citalopram 20-40mg, escitalopram 10-20mg, paroxetine 20-60mg; fluoxetine 20-80mg
12 weeks of individual cognitive behavioral therapy
Outcomes
Primary Outcome Measures
Brain NVS Construct Measure (Composite)
Brain: functional magnetic resonance imaging (fMRI) BOLD percent signal change [PSC] within region of interests [ROIs: amygdala, bed nucleus of stria terminalis, striatum, hippocampus, anterior cingulate cortex (including dorsal, rostral, & subgenual subdivisions), anterior insula, ventro/dorso-medial prefrontal cortex, orbitofrontal cortex, ventro/dorso-lateral prefrontal cortex for Emotional Face Assessment Task (EFAT), Emotional Face Interference Task (EFIT), Contextual Threat Task (CTT), Emotion Regulation Task (ERT)
Secondary Outcome Measures
Full Information
NCT ID
NCT01903447
First Posted
July 9, 2013
Last Updated
October 9, 2018
Sponsor
University of Illinois at Chicago
Collaborators
National Institutes of Health (NIH), National Institute of Mental Health (NIMH)
1. Study Identification
Unique Protocol Identification Number
NCT01903447
Brief Title
Negative Valence Brain Targets and Predictors of Anxiety and Depression Treatment
Official Title
Negative Valence Brain Targets and Predictors of Anxiety and Depression Treatment
Study Type
Interventional
2. Study Status
Record Verification Date
January 2018
Overall Recruitment Status
Completed
Study Start Date
December 13, 2013 (Actual)
Primary Completion Date
February 21, 2018 (Actual)
Study Completion Date
February 21, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Illinois at Chicago
Collaborators
National Institutes of Health (NIH), National Institute of Mental Health (NIMH)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Internalizing psychopathologies (IPs) involving depression and anxiety are among the most prevalent, costly and disabling illnesses. Treatments for IPs are available but the extent to which individual patients respond is quite heterogeneous. Little information exists, particularly in the biological domain, which helps to explain individual differences in treatment response. IPs share similar patterns of dysfunction within the Fronto-Limbic Affect Regulation and Emotional Salience (FLARES) brain circuit, and two commonly used, 'gold standard' treatments - selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioral therapies (CBTs) - are equally effective for both anxiety and depressive disorders, and appear to change brain activity in the same areas within the FLARES circuit. The overarching goal of the project is delineate what are common versus specific FLARE brain targets for SSRI and CBT and identify specific aspects of FLARE dysfunction that might better predict response to both and to a specific modality of treatment. This experiment integrates emotion and its interaction with cognition across several stages of emotional experience, encompassing studies that probe sensitivity to acute and potential threat and automatic and volitional forms of affect regulation in relation to the FLARES brain network.
We will enroll 200 patients presenting to our Mood and Anxiety Disorders Program seeking treatment for disabling 'anxiety, worry, depressed mood' (IPs, including those characterized as Not Otherwise Specified) and randomize them to a 12-week course of SSRI or CBT. Dimensional, transdiagnostic negative valence systems (NVS) constructs, including FLARES function, will be measured before and after each treatment. Specifically, the project will examine 2 Specific Aims: 1) Where and how do SSRI and CBT treatments exert their effects on NVS constructs?; and 2) Which NVS construct can predict the likelihood of success from SSRI and CBT treatment? Such findings can be used to guide the right patients to the right treatments with the highest likelihood of success. They also elucidate a pathophysiologically-driven mechanistic model of where and how treatments work in the brain and thus hasten the development of new treatments that target the underlying pathophysiology across internalizing conditions.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Internalizing Psychopathologies (IPs) Depression and Anxiety
Keywords
Internalizing psychopathologies, Depression, Anxiety, MRI, medication treatment, psychotherapy, brain function
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
271 (Actual)
8. Arms, Groups, and Interventions
Arm Title
SSRI
Arm Type
Active Comparator
Arm Description
sertraline: 100-200mg, citalopram 20-40mg, escitalopram 10-20mg, paroxetine 20-60mg; fluoxetine 20-80mg
Arm Title
CBT
Arm Type
Active Comparator
Arm Description
12 weeks of individual cognitive behavioral therapy
Intervention Type
Drug
Intervention Name(s)
SSRI
Intervention Type
Behavioral
Intervention Name(s)
CBT
Primary Outcome Measure Information:
Title
Brain NVS Construct Measure (Composite)
Description
Brain: functional magnetic resonance imaging (fMRI) BOLD percent signal change [PSC] within region of interests [ROIs: amygdala, bed nucleus of stria terminalis, striatum, hippocampus, anterior cingulate cortex (including dorsal, rostral, & subgenual subdivisions), anterior insula, ventro/dorso-medial prefrontal cortex, orbitofrontal cortex, ventro/dorso-lateral prefrontal cortex for Emotional Face Assessment Task (EFAT), Emotional Face Interference Task (EFIT), Contextual Threat Task (CTT), Emotion Regulation Task (ERT)
Time Frame
Change from Week 0 to Week 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Generally medically and neurologically healthy
Chief complaint(s) of "anxiety, worry, and/or depressed mood
Exclusion Criteria:
Current or past manic/hypomanic episode or psychotic symptoms
Suicidal ideation
Presence of contraindications (e.g., history of SSRI adverse events) or prior history of SSRI resistance (no response to > 2 SSRI trials with adequate duration and dose)
Obsessive compulsive disorder (OCD)
Current cognitive dysfunction (traumatic brain injury, mental retardation, dementia)
Current alcohol and substance dependence
Ongoing therapy/medication treatment of any kind outside of this study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
K. Luan Phan, MD
Organizational Affiliation
University of Illinois at Chicago
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Illinois at Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60608
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
34274600
Citation
Kinney KL, Burkhouse KL, Chang F, MacNamara A, Klumpp H, Phan KL. Neural mechanisms and predictors of SSRI and CBT treatment of anxiety: A randomized trial focused on emotion and cognitive processing. J Anxiety Disord. 2021 Aug;82:102449. doi: 10.1016/j.janxdis.2021.102449. Epub 2021 Jul 10.
Results Reference
derived
PubMed Identifier
31060042
Citation
Gorka SM, Young CB, Klumpp H, Kennedy AE, Francis J, Ajilore O, Langenecker SA, Shankman SA, Craske MG, Stein MB, Phan KL. Emotion-based brain mechanisms and predictors for SSRI and CBT treatment of anxiety and depression: a randomized trial. Neuropsychopharmacology. 2019 Aug;44(9):1639-1648. doi: 10.1038/s41386-019-0407-7. Epub 2019 May 6.
Results Reference
derived
PubMed Identifier
29894598
Citation
Burkhouse KL, Gorka SM, Klumpp H, Kennedy AE, Karich S, Francis J, Ajilore O, Craske MG, Langenecker SA, Shankman SA, Hajcak G, Phan KL. Neural Responsiveness to Reward as an Index of Depressive Symptom Change Following Cognitive-Behavioral Therapy and SSRI Treatment. J Clin Psychiatry. 2018 Jun 12;79(4):17m11836. doi: 10.4088/JCP.17m11836.
Results Reference
derived
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Negative Valence Brain Targets and Predictors of Anxiety and Depression Treatment
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