Novel Neural Circuit Biomarkers of Major Depression Response to CCBT

NCT03096886 | Completed Results

• 1 other identifier: R01MH110939-01A1
• Study Type: interventional
• Target: 132
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to learn more about computer-assisted cognitive behavioral therapy or "CCBT" and to examine connections in the brains of patients with depression. CCBT is approved by the FDA as a form of treatment for depression. It is done partly on the computer and partly with a therapist. This study will enroll participants with depression and participants without depression. The investigators will recruit a total of 100 participants: 80 with Major Depressive Disorder (MDD) and 50 matched comparison participants. Healthy control subjects will participate for approximately 8 weeks. All MDD participants will receive CCBT. Half of the MDD participants will all receive computer-augmented skills training with the Good Days Ahead (GDA) protocol immediately (Early CCBT). Early CCBT subjects will participate for approximately 8 weeks. The other half of the MDD participants initially will be randomized to a waitlist of up to 4 weeks and subsequently will receive CCBT treatment (Late CCBT). Late CCBT subjects will participate for approximately 12 weeks. All participants are asked to complete a screening, which includes a series of clinical interviews and self-report questionnaires about the individual's thoughts, moods, and behaviors. All participants are asked to wear an actigraph, which is a watch-like device that measures activity levels. Additionally, participants are asked to completed short questions and have their activity levels monitored through phone app(s). All participants (Healthy Control and MDD participants) will receive functional magnetic resonance imaging (fMRI) scanning at baseline. Early CCBT participants will receive fMRI scanning after 8 weeks of CCBT, and Late CCBT participants will receive fMRI scanning at the conclusion of the waitlist and after the 8-week course of CCBT. Brain activity will be compared between MDD and controls at baseline and between Early CCBT vs Late CCBT. The 2nd and 3rd brain scans of Late CCBT participants at the end of the waitlist and 8-week course of CCBT, respectively, will allow within-subject comparison of CCBT vs Waitlist treatment effects. This clinical trial has two IRB protocol numbers: 826910 and 832295. The data collected through both protocol numbers will be analyzed together to accomplish the target of 100 subjects for this clinical trial.

Conditions

Depression; Major Depressive Disorder; Depressive Disorder; Depression, Unipolar

Keywords

Cognitive Behavioral Therapy; Computer-Assisted Cognitive Behavioral Therapy; Computer-Augmented Cognitive Behavioral Therapy; CBT; Computer-Assisted CBT; Computer-Augmented CBT

Outcome Measures

Primary Outcomes (1)

• Resting State Functional Connectivity: MDD vs Controls

  Compare baseline resting state functional connectivity and task-induced activity between MDD (early and late CCBT combined) and controls. The connectivity values were Z-normalized Pearson's r values. Specifically, time series values were averaged across all voxels within each given Region Of Interest (ROI) (Left Dorsolateral Prefrontal Cortex and Subgenual Anterior Cingulate Cortex). For each study visit for each participant, the resulting region-wise time series values were then correlated with those from another ROI using a Pearson correlation. This correlation coefficient was then Z-normalized to yield the connectivity value. Improvement was defined as connectivity that is closer to negative (less positive). There is no relevant clinical threshold.

  Baseline

Secondary Outcomes (1)

• Resting State Functional Connectivity: Immediate CCBT vs Waitlist Followed by CCBT

  Week 8

Study Arms (3)

Early CCBT

EXPERIMENTAL

Intervention: Computer-Augmented Cognitive Behavioral Therapy Half of participants presenting with MDD will be randomized to receive 8 weeks of Computer-Augmented Cognitive Behavior Therapy (CCBT) immediately after completing pre-treatment assessments; imaging data will be collected pre- and post-treatment.

Behavioral: Computer-Augmented Cognitive Behavioral Therapy

Late CCBT

EXPERIMENTAL

Intervention: Waitlist followed by Computer-Augmented Cognitive Behavioral Therapy Half of participants presenting with MDD will be randomized to be waitlisted for up to 4 weeks and will receive CCBT within 4 weeks; imaging data will also be collected pre--treatment, following waitlist, and post-treatment of CCBT. This arm will serve as the equivalent of a "placebo comparator" arm during the waitlist; and then as an experimental arm when receiving 8 weeks of CCBT treatment.

Behavioral: Computer-Augmented Cognitive Behavioral Therapy

Matched Comparison

NO INTERVENTION

No Intervention: Matched Comparison Healthy controls will act as a matched comparator. Participants will complete pre-treatment assessments and imaging.

Interventions

Computer-Augmented Cognitive Behavioral Therapy BEHAVIORAL

The model of CCBT, "Good Days Ahead" (GDA) will be utilized, it has been found that it is not inferior to CBT in MDD treatment efficacy. CCBT participants will complete 9 modules of the GDA program, including 240 minutes of computer training; participants will also meet with a therapist on 6 occasions for a total of 180 minutes of clinician administered cognitive behavioral therapy.

Also known as: CCBT, Computer-Assisted Cognitive Behavioral Therapy

Early CCBT; Late CCBT

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Adults 18 - 60 years old, gender inclusive
• Willing to not take psychotropic medications for the duration of the study
• Fluent in English (both verbally and written)
• Able and willing to provide consent
• Has reliable access to a private computer or electronic tablet
• Owns a smart phone (iPhone or Android) with ability to download apps
• Experimental group 1) Diagnosis of MDD, experiencing current episode as determined by SCID-5 2) Current major depressive episode of moderate severity, as determined by MADRS score of 20 or higher
• Control group 1) No history of MDD in lifetime 2) No indication of current, significant depressive symptoms, as determined by MADRS score of 8 or lower

You may not qualify if:

• Diagnosis of severe or poorly controlled concurrent medical disorders that may cause depression or require medication that could cause depressive symptoms
• Unwilling to provide informed consent
• Diagnosis of concurrent DSM-5 (SCID) psychiatric disorders: any psychotic or organic mental disorder, bipolar disorder, active alcohol or drug dependence, primary anxiety disorder or primary eating disorders (primary refers to the diagnosis associated with the most functional impairment)
• Diagnosed (DSM-5 criteria) by the clinical coordinator with attention deficit hyperactivity disorder, learning disorder, borderline personality disorder, antisocial personality disorder, or paranoid personality disorder
• Cannot complete questionnaires written in English
• Have not completed at least a 10th grade education or a general education degree (GED)
• Represent an active suicide risk
• Centrally acting antiadrenergic agents
• Have MRI contraindications (e.g., foreign metallic implants, pacemaker, severe claustrophobia)
• Currently demonstrating a response to antidepressant/psychotropic medication (besides SSRIs, which are acceptable if use has been stable over at least a 2 month period)
• Experimental group 1) Score less than 20 on the MADRS at either initial interview or 18 at second interview 2) Have previously failed to respond to a trial of at least 8 weeks of CBT conducted by a certified therapist) 3) Are currently demonstration a response to antidepressant/psychotropic medication besides SSRIs, which are acceptable if use has been stable over at least a 2 month period (individuals taking a psychotropic medication may stop taking it for the purpose of the study ONLY if they are not receiving clinical benefits from taking it and after meeting with one of the study doctors to discuss the risks/benefits of discontinuing the medication and other treatment options)
• Control group 1) Must have no lifetime history of a major depressive episode 2) Must score below 8 on the MADRS

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19144, United States

Location

Related Publications (18)

• Shou H, Yang Z, Satterthwaite TD, Cook PA, Bruce SE, Shinohara RT, Rosenberg B, Sheline YI. Cognitive behavioral therapy increases amygdala connectivity with the cognitive control network in both MDD and PTSD. Neuroimage Clin. 2017 Jan 27;14:464-470. doi: 10.1016/j.nicl.2017.01.030. eCollection 2017.

  PMID: 28275546 BACKGROUND

• Newman MG, Szkodny LE, Llera SJ, Przeworski A. A review of technology-assisted self-help and minimal contact therapies for anxiety and depression: is human contact necessary for therapeutic efficacy? Clin Psychol Rev. 2011 Feb;31(1):89-103. doi: 10.1016/j.cpr.2010.09.008. Epub 2010 Oct 14.

  PMID: 21130939 BACKGROUND

• Vittengl JR, Clark LA, Jarrett RB. Continuation-phase cognitive therapy's effects on remission and recovery from depression. J Consult Clin Psychol. 2009 Apr;77(2):367-71. doi: 10.1037/a0015238.

  PMID: 19309197 BACKGROUND

• Biesheuvel-Leliefeld KE, Kok GD, Bockting CL, Cuijpers P, Hollon SD, van Marwijk HW, Smit F. Effectiveness of psychological interventions in preventing recurrence of depressive disorder: meta-analysis and meta-regression. J Affect Disord. 2015 Mar 15;174:400-10. doi: 10.1016/j.jad.2014.12.016. Epub 2014 Dec 13.

  PMID: 25553400 BACKGROUND

• Seligman ME. The effectiveness of psychotherapy. The Consumer Reports study. Am Psychol. 1995 Dec;50(12):965-74. doi: 10.1037//0003-066x.50.12.965.

  PMID: 8561380 BACKGROUND

• Andersson G, Cuijpers P. Internet-based and other computerized psychological treatments for adult depression: a meta-analysis. Cogn Behav Ther. 2009;38(4):196-205. doi: 10.1080/16506070903318960.

  PMID: 20183695 BACKGROUND

• Wright JH, Wright AS, Albano AM, Basco MR, Goldsmith LJ, Raffield T, Otto MW. Computer-assisted cognitive therapy for depression: maintaining efficacy while reducing therapist time. Am J Psychiatry. 2005 Jun;162(6):1158-64. doi: 10.1176/appi.ajp.162.6.1158.

  PMID: 15930065 BACKGROUND

• Eells TD, Barrett MS, Wright JH, Thase M. Computer-assisted cognitive-behavior therapy for depression. Psychotherapy (Chic). 2014 Jun;51(2):191-7. doi: 10.1037/a0032406. Epub 2013 Sep 23.

  PMID: 24059735 BACKGROUND

• Korgaonkar MS, Fornito A, Williams LM, Grieve SM. Abnormal structural networks characterize major depressive disorder: a connectome analysis. Biol Psychiatry. 2014 Oct 1;76(7):567-74. doi: 10.1016/j.biopsych.2014.02.018. Epub 2014 Mar 6.

  PMID: 24690111 BACKGROUND

• Mayberg HS. Limbic-cortical dysregulation: a proposed model of depression. J Neuropsychiatry Clin Neurosci. 1997 Summer;9(3):471-81. doi: 10.1176/jnp.9.3.471.

  PMID: 9276848 BACKGROUND

• Drevets WC, Price JL, Furey ML. Brain structural and functional abnormalities in mood disorders: implications for neurocircuitry models of depression. Brain Struct Funct. 2008 Sep;213(1-2):93-118. doi: 10.1007/s00429-008-0189-x. Epub 2008 Aug 13.

  PMID: 18704495 BACKGROUND

• Sheline YI, Barch DM, Donnelly JM, Ollinger JM, Snyder AZ, Mintun MA. Increased amygdala response to masked emotional faces in depressed subjects resolves with antidepressant treatment: an fMRI study. Biol Psychiatry. 2001 Nov 1;50(9):651-8. doi: 10.1016/s0006-3223(01)01263-x.

  PMID: 11704071 BACKGROUND

• Hamilton JP, Etkin A, Furman DJ, Lemus MG, Johnson RF, Gotlib IH. Functional neuroimaging of major depressive disorder: a meta-analysis and new integration of base line activation and neural response data. Am J Psychiatry. 2012 Jul;169(7):693-703. doi: 10.1176/appi.ajp.2012.11071105.

  PMID: 22535198 BACKGROUND

• Zhang J, Wang J, Wu Q, Kuang W, Huang X, He Y, Gong Q. Disrupted brain connectivity networks in drug-naive, first-episode major depressive disorder. Biol Psychiatry. 2011 Aug 15;70(4):334-42. doi: 10.1016/j.biopsych.2011.05.018.

  PMID: 21791259 BACKGROUND

• Kaiser M. A tutorial in connectome analysis: topological and spatial features of brain networks. Neuroimage. 2011 Aug 1;57(3):892-907. doi: 10.1016/j.neuroimage.2011.05.025. Epub 2011 May 14.

  PMID: 21605688 BACKGROUND

• Fales CL, Barch DM, Rundle MM, Mintun MA, Snyder AZ, Cohen JD, Mathews J, Sheline YI. Altered emotional interference processing in affective and cognitive-control brain circuitry in major depression. Biol Psychiatry. 2008 Feb 15;63(4):377-84. doi: 10.1016/j.biopsych.2007.06.012. Epub 2007 Aug 24.

  PMID: 17719567 BACKGROUND

• Satterthwaite TD, Cook PA, Bruce SE, Conway C, Mikkelsen E, Satchell E, Vandekar SN, Durbin T, Shinohara RT, Sheline YI. Dimensional depression severity in women with major depression and post-traumatic stress disorder correlates with fronto-amygdalar hypoconnectivty. Mol Psychiatry. 2016 Jul;21(7):894-902. doi: 10.1038/mp.2015.149. Epub 2015 Sep 29.

  PMID: 26416545 BACKGROUND

• Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979 Apr;134:382-9. doi: 10.1192/bjp.134.4.382.

  PMID: 444788 BACKGROUND

MeSH Terms

Conditions

Depression; Depressive Disorder, Major; Depressive Disorder

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Mood Disorders; Mental Disorders

Results Point of Contact

• Title: Dr. Yvette Sheline
• Organization: University of Pennsylvania

sheline@pennmedicine.upenn.edu

(215) 573-0082

Study Officials

• Yvette I Sheline, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: An experienced clinical evaluator with established reliability will assess patients pre-treatment and biweekly during CCBT treatment (Weeks 1, 2, 4, 6, 8, 9 of CCBT). All evaluations will be conducted without knowledge of treatment assignment. The evaluator will assess symptom severity according to the MADRS and Hamilton Rating Scale for Depression (HAM-D). Evaluators will have offices remote to the day-to-day operations of the treatment study and will not participate in weekly study management meetings in order to help preserve the blind.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a 3-arm, parallel study design. Individuals presenting with MDD will be randomized into either Arm 1: 8 weeks of Computer-Augmented Cognitive Behavioral Therapy (CCBT) Immediately or Arm 2: Waitlist up to 4 weeks followed by 8 weeks of CCBT. Arm 3 is a no treatment arm for matched comparison participants (i.e., healthy controls).

Study Record Dates

• First Submitted: March 24, 2017
• First Posted: March 30, 2017
• Study Start: June 5, 2017
• Primary Completion: October 23, 2023
• Study Completion: October 23, 2023
• Last Updated: December 5, 2024
• Results First Posted: December 5, 2024

Record last verified: 2024-11

Locations

US (1)