Transdiagnostic Brain-Behavior Profiling to Enhance Cognitive Behavioral Therapy Response

NCT03175068 | Completed Results DMC

• 2 other identifiers: 2017-02581R01MH112705-01A1
• Study Type: interventional
• Target: 203
• Locations: 1 country
• Sites: 1

Brief Summary

Many patients with Major Depressive Disorder (MDD) and generalized Social Anxiety Disorder (gSAD) are treated with cognitive behavioral therapy (CBT) but few have meaningful improvement. MDD and gSAD are diseases of brain dysfunction that manifest as impaired emotion regulation; CBT teaches emotion regulation strategies but how it works in the brain remains largely unknown. Individual differences in brain function related to emotion regulation may make some patients better suited for CBT and CBT may remedy the brain dysfunction that underlies these disorders. This project will compare CBT with a placebo psychotherapy (i.e., supportive therapy) in MDD and gSAD to test, validate, and refine brain-based markers and examine mechanisms of change to examine how CBT works and for whom.

Conditions

Major Depressive Disorder; Social Anxiety Disorder

Keywords

Functional magnetic resonance imaging; Electroencephalography; Cognitive Behavioral Therapy; Supportive Therapy

Outcome Measures

Primary Outcomes (5)

• Changes in Symptom Severity From Baseline to Week 12 Between Treatment Arms

  Patients were randomized to either 12 weeks of cognitive behavioral therapy or supportive therapy. Healthy control (HC) participants did not receive treatment but completed the same assessments at the same time points as patients. Liebowitz Social Anxiety Scale (LSAS) and Hamilton Depression Rating Scale (HDRS) served as primary outcome measures as they are interviewer based standard clinical measures. A composite score combining LSAS and HDRS was constructed using proportion of maximum scaling (POMS) method to represent symptom severity. Higher scores mean worse outcomes. The minimum value is 0 and the maximum value is 1.

  baseline and week 12

• Baseline Brain Activity During Emotion Regulation Differences Between Controls and Patients

  Outcomes are parameter estimates (arbitrary units) of brain activity for a priori brain regions of interest (bilateral amygdala, bilateral dorsolateral prefrontal cortex ('DLPFC'), bilateral inferior frontal gyrus ('IFG')) comparing brain activity during task conditions against a baseline condition (look at neutral images; 'Look Neut'). Task conditions are reappraising negative images ('Reappraise') and looking at negative images ('Look Neg'). The Reappraise vs. Look Neut and Look Neg vs. Look Neut are the contrasts of interest. Not all participants who consented to the study completed this task at all time points. Reasons include dropping out of the study, COVID shutdowns, scheduling issues, and participants not consenting to perform task due to use of negative images. Higher values represent greater activation.

  baseline

• Comparisons Between Emotion Regulation Task Brain Activity at Baseline and After Completing Therapy (12 Weeks).

  Planned comparisons (i.e., paired t-test). Outcomes are parameter estimates (arbitrary units) of brain activity for a priori brain regions (amygdala, dorsolateral prefrontal cortex (DLPFC), inferior frontal gyrus (IFG)) comparing reappraising negative images ('Reappraise') to baseline condition (look at neutral images; 'Look Neut'). Not all participants who consented to the study completed this task at all time points. Reasons include dropping out of the study, COVID shutdowns, scheduling issues, and participants not consenting to perform task due to use of negative images. Higher values represent greater activation.

  baseline and 12 weeks

• Baseline Brain Activity During Emotion Regulation as a Predictor of Psychotherapy Outcome Collapsed Across Treatment Arm.

  Outcomes are baseline parameter estimates (arbitrary units) of brain activity for a priori brain regions of interest (bilateral amygdala, bilateral dorsolateral prefrontal cortex ('DLPFC'), bilateral inferior frontal gyrus ('IFG')) comparing active conditions against 'baseline' condition (i.e., look at neutral images; 'Look Neut'). Active conditions are reappraising negative images ('Reappraise') and looking at negative images ('Look Neg'). The Reappraise vs. Look Neut and Look Neg vs. Look Neut are the contrasts of interest. Other outcome measure is symptom severity before and after psychotherapy collapsing across cognitive behavioral therapy and supportive therapy to examine general psychotherapy predictors across psychotherapies. Higher values (arbitrary units) represent greater activation. Aim 5 is a continuation of Aim 4 including symptom measures comprised of HAMD and LSAS composite score of maximum scaling method.

  baseline

• Baseline Brain Activity During Emotion Regulation as a Predictor of Psychotherapy Outcome Collapsed Across Treatment Arm.

  This aim is connected to Aim 4 and represents an additional predictor in the regression model. Data analysis results for Aim 4 apply to this data as well. Outcome measure is symptom severity before and after psychotherapy collapsing across cognitive behavioral therapy and supportive therapy. Symptom measures comprised social anxiety (LSAS) and depression (HAMD) composite score proportion of maximum scaling method which ranges from 0 to 1. Higher symptom severity scores represent worse symptoms.

  baseline and 12 weeks

Study Arms (2)

CBT

ACTIVE COMPARATOR

The clinical psychologist will use a manualized CBT approach tailored to MDD or gSAD. Over a 12-week period sessions will include core CBT strategies -- psychoeducation, cognitive intervention (e.g., cognitive restructuring), behavioral changes (i.e., fear exposure, behavioral activation strategies) and relapse prevention.

Behavioral: CBT

ST

PLACEBO COMPARATOR

The clinical psychologist will use an ST approach that resembles client-centered therapy of Carl Rogers (1951) which has been used as a control psychotherapy. The manual is based on supportive psychotherapy principles. Over a 12-week period, sessions will emphasize reflective listening and elicitation of affect. In contrast to CBT, therapists allow patients to determine the focus of each session, pulling for emotion, validating emotions when possible, and offering empathetic comments. Therapists will refrain from delineating any CBT theoretical framework and avoided cognitive and behavioral techniques that might overlap with CBT.

Behavioral: ST

Interventions

CBT BEHAVIORAL

CBT works by changing people's attitudes and their behavior by focusing on the thoughts, images, beliefs and attitudes that are held (a person's cognitive processes) and how these processes relate to the way a person behaves, as a way of dealing with emotional problems.

Also known as: Cognitive Behavioral Therapy

CBT

ST BEHAVIORAL

Treatment designed to improve, reinforce, or sustain a patient's physiological well-being or psychological self-esteem and self-reliance

Also known as: Supportive Therapy

ST

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• generally medically and neurologically healthy, including no evidence of mental retardation or serious cognitive impairment that would interfere with protocol adherence and/or task performance
• between the ages of 18 - 65 years old, inclusive
• right-handed
• primary diagnosis of MDD or gSAD based on the SCID DSM-5. Patients will be permitted to have limited comorbid and/or history of internalizing psychopathologies (e.g., generalized anxiety disorder, specific phobia, adjustment disorder)

You may not qualify if:

• personal current or past manic/hypomanic episode or psychotic symptoms
• active suicidal ideation as determined by the Columbia Suicide Severity Rating Scale (C-SSRS)
• prior history of standard CBT (failure or success)
• any current or recent (past 4 weeks) use of medication (prescription or non-prescription) with psychotropic effects
• psychotherapy other than CBT or psychotropic medication use during the study
• cognitive dysfunction (traumatic brain injury, mental retardation, dementia)
• active moderate or severe alcohol and/or substance use disorders
• For healthy controls: history or current Axis I disorder.
• presence of ferrous-containing metals within the body (e.g., aneurysm clips, shrapnel/retained particles)
• inability to tolerate small, enclosed spaces without anxiety (e.g., claustrophobia)

Sponsors & Collaborators

• University of Illinois at Chicago: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

University of Illinois at Chicago

Chicago, Illinois, 60608, United States

Location

Related Publications (1)

• Feurer C, Jimmy J, Bhaumik R, Duffecy J, Medrano GR, Ajilore O, Shankman SA, Langenecker SA, Craske MG, Phan KL, Klumpp H. Anterior cingulate cortex activation during attentional control as a transdiagnostic marker of psychotherapy response: a randomized clinical trial. Neuropsychopharmacology. 2022 Jun;47(7):1350-1357. doi: 10.1038/s41386-021-01211-2. Epub 2021 Oct 30.

  PMID: 34718341 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major; Phobia, Social

Interventions

Cognitive Behavioral Therapy; Palliative Care

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Phobic Disorders; Anxiety Disorders

Intervention Hierarchy (Ancestors)

Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities; Patient Care; Therapeutics; Health Services; Health Care Facilities Workforce and Services

Limitations and Caveats

Not all participants completed all tasks at all time points for various reasons (e.g., attrition), which reduced power to test hypotheses. During COVID shutdowns, psychotherapy sessions changed from in-person to secure telehealth. COVID shutdowns interfered with data collection, particularly in the lab (e.g., fMRI). Analytic approaches used in ClinicalTrials.gov may not reflect approaches used in published results.

Results Point of Contact

• Title: Heide Klumpp, PhD
• Organization: University of Illinois at Chicago

hklumpp@uic.edu

312-996-0416

Study Officials

• Heide Klumpp, PhD

  University of Illinois at Chicago

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: May 31, 2017
• First Posted: June 5, 2017
• Study Start: July 5, 2017
• Primary Completion: March 1, 2022
• Study Completion: March 1, 2022
• Last Updated: June 23, 2026
• Results First Posted: June 23, 2026

Record last verified: 2026-05

Locations

US (1)