NCT01903447

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
271

participants targeted

Target at P75+ for phase_4

Timeline
Completed

Started Dec 2013

Longer than P75 for phase_4

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 9, 2013

Completed
10 days until next milestone

First Posted

Study publicly available on registry

July 19, 2013

Completed
5 months until next milestone

Study Start

First participant enrolled

December 13, 2013

Completed
4.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 21, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 21, 2018

Completed
Last Updated

October 11, 2018

Status Verified

January 1, 2018

Enrollment Period

4.2 years

First QC Date

July 9, 2013

Last Update Submit

October 9, 2018

Conditions

Internalizing Psychopathologies (IPs) Depression and Anxiety

Keywords

Internalizing psychopathologiesDepressionAnxietyMRImedication treatmentpsychotherapybrain function

Outcome Measures

Primary Outcomes (1)

  • 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)

    Change from Week 0 to Week 12

Study Arms (2)

SSRI

ACTIVE COMPARATOR

sertraline: 100-200mg, citalopram 20-40mg, escitalopram 10-20mg, paroxetine 20-60mg; fluoxetine 20-80mg

Drug: SSRI

CBT

ACTIVE COMPARATOR

12 weeks of individual cognitive behavioral therapy

Behavioral: CBT

Interventions

SSRIDRUG
SSRI
CBTBEHAVIORAL
CBT

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Generally medically and neurologically healthy
  • Chief complaint(s) of "anxiety, worry, and/or depressed mood

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Illinois at Chicago

Chicago, Illinois, 60608, United States

Location

Related Publications (3)

  • 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.

    PMID: 34274600DERIVED

  • 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.

    PMID: 31060042DERIVED

  • 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.

    PMID: 29894598DERIVED

MeSH Terms

Conditions

Ichthyosis prematurity syndromeDepressionAnxiety Disorders

Condition Hierarchy (Ancestors)

Behavioral SymptomsBehaviorMental Disorders

Study Officials

  • K. Luan Phan, MD

    University of Illinois at Chicago

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor of Psychiatry, Director

Study Record Dates

First Submitted

July 9, 2013

First Posted

July 19, 2013

Study Start

December 13, 2013

Primary Completion

February 21, 2018

Study Completion

February 21, 2018

Last Updated

October 11, 2018

Record last verified: 2018-01

Locations

US(1)