DepressionNCT03096886
Novel Neural Circuit Biomarkers of Major Depression Response to CCBT
A study testing Computer-Augmented Cognitive Behavioral Therapy in people with Depression and Major Depressive Disorder, run by University of Pennsylvania at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Depression, Major Depressive Disorder, Depressive Disorder
- What is being tested?
- Computer-Augmented Cognitive Behavioral Therapy
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 132 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Jun 2017to 23 Oct 2023
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pennsylvania
Philadelphia, Pennsylvania, 19144
About this study
Official title: Novel Neural Circuit Biomarkers of Major Depression Response to Computer-augmented CBT
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.
Read more
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.
Read the detailed description
This study is a randomized study. 80 subjects with MDD will be randomly assigned (1:1) to immediately receive 8 weeks of CCBT or delayed treatment, consisting of up to 4 weeks of waitlist, followed by 8 weeks of CCBT. 50 healthy controls of similar age/sex will be recruited to serve as a comparison group for baseline magnetic resonance imaging (MRI) scanning.
The study will enroll subjects for approximately 4 years (~2 subjects per month for 48 months). The length of subject participation will vary based on what group the participants are randomized to. Healthy controls will participate for approximately 8 weeks. Subjects with MDD who were randomized to Early CCBT will participate for approximately 8 weeks; subjects with MDD who were randomized to Late CCBT will participate for approximately 12 weeks. Variability in the study duration for each group depends on each subjects' personal availability for visits and the availability of the magnetic resonance scanner.
Potential participants will complete a phone screen to determine eligibility. If the individual is eligible, the individual will be scheduled for an in-person screening visit. Information collected during the phone screening will not be used in the data analysis; phone screening information will be collected and retained in REDCap. Remote contact options are available as needed/possible.
Screening Visit - all participants will have the study described to them in detail, including the risks and study procedures as outlined in the informed consent form and will sign the informed consent form (ICF) and HIPAA authorization, prior to any study procedures being completed. Participants will be screened for symptoms of psychological disorders and severity of major depressive symptoms by a trained research team member.
If determined eligible, HEALTHY CONTROLS will be scheduled for return to complete an fMRI scan and baseline visit, in which self-report measures, including reports of mood, behavior, and thoughts will be collected, as well as neuropsychological testing. The HIPAA-compliant phone app Beiwe and actigraph setup will take place during the baseline visit. Participants will complete mood monitoring questions on the phone app and also have their activity levels monitored by the phone app and the actigraph for the duration of the study.
If determined eligible at screening, MDD (EXPERIMENTAL GROUP) participants will be randomized (1:1) as follows: One half of the depressed participants will be randomized to receive 8 weeks of CCBT immediately after completing pretreatment assessments and the remainder will be randomized to a waitlist of up to 4 weeks followed by 8 weeks of CCBT.
MDD, EARLY CCBT GROUP Early CCBT participants will be scheduled for return to complete an fMRI scan at the baseline visit, in which self-report measures, including reports of mood, behavior, and thoughts will be collected, as well as neuropsychological testing. The phone apps Beiwe and Ethica and actigraph setup will take place during the baseline visit. Participants will complete mood monitoring questions on the phone apps and also have their activity levels monitored by the phone app and the actigraph for the duration of the study. Participants will complete Good Days Ahead (GDA) computer training throughout the 8 weeks of CCBT, and having 6 encounters with a licensed psychologist/psychiatrist. Additionally, outcome measures will be assessed by an independent clinical evaluator (without knowledge of treatment assignment) every other week. As soon as can be arranged after Week 9 of CCBT treatment (last CCBT Clinical Contact), participants will return to complete an fMRI scan and end of study visit, in which self-report measures, including reports of mood, behavior, and thoughts will be collected, as well as neuropsychological testing.
MDD, LATE CCBT GROUP Late CCBT participants will be scheduled for return to complete an fMRI scan and baseline visit, in which self-report measures, including reports of mood, behavior, and thoughts will be collected, as well as neuropsychological testing. The phone apps Beiwe and Ethica and actigraph setup will take place during the baseline visit. During the 2-4 week waitlist phase, participants will complete mood monitoring questions on the phone apps and also have their activity levels monitored by the phone app and the actigraph.
At the conclusion of the waitlist of up to 4 weeks, participants will complete a second fMRI scan and complete self-report measures, including reports of mood, behavior, and thoughts will be collected, as well as neuropsychological testing.
Participants will then enter the CCBT phase and will complete Good Days Ahead (GDA) computer training throughout the 8 weeks of CCBT. They will have 6 encounters with a licensed psychologist/psychiatrist at multiple time points during this period. Additionally, outcome measures will be assessed by an independent clinical evaluator (without knowledge of treatment assignment) every other week during this study phase. At Week 9 of CCBT treatment (last CCBT Clinical Contact), participants will complete a 1-hour fMRI scan and self-report measures, including reports of mood, behavior, and thoughts will be collected, as well as neuropsychological testing.
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 130 subjects for this clinical trial.
- Being tested
- Computer-Augmented Cognitive Behavioral Therapy
- Keywords
- Cognitive Behavioral Therapy, Computer-Assisted Cognitive Behavioral Therapy, Computer-Augmented Cognitive Behavioral Therapy, CBT, Computer-Assisted CBT, Computer-Augmented CBT
- Medical subject headings
- Depression, Depressive Disorder, Major, Depressive Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Computer-Augmented Cognitive Behavioral TherapyBehavioural
Also called CCBT, Computer-Assisted Cognitive Behavioral Therapy
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline
Secondary outcomes (1)
Resting State Functional Connectivity: Immediate CCBT vs Waitlist Followed by CCBT
Assess CCBT treatment effects on resting state functional connectivity and task-induced activity in MDD comparing Immediate CCBT treatment vs Waitlist followed by CCBT at 8 weeks. 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.
Measured: Week 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Mar 2017
- Study start5 Jun 2017
- Primary completion23 Oct 2023
- Study completion23 Oct 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (19)Papers the sponsor has linked to this study.
- Other trials for DepressionStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe 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
- Model description
- 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).
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 132 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Yvette I Sheline, MD, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03096886
- Sponsor's protocol ID
- R01MH110939-01A1
- Status last verified
- Nov 2024
- First submitted
- 24 Mar 2017
- Last updated
- 5 Dec 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 28275546Newman 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.
PubMed 21130939Vittengl 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.
PubMed 19309197Biesheuvel-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.
PubMed 25553400Seligman 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.
PubMed 8561380Andersson 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.
PubMed 20183695Wright 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.
PubMed 15930065Eells 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.
PubMed 24059735Korgaonkar 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.
PubMed 24690111Mayberg 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.
PubMed 9276848Drevets 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.
PubMed 18704495Sheline 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.
PubMed 11704071Hamilton 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.
PubMed 22535198Zhang 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.
PubMed 21791259Kaiser 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.
PubMed 21605688
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Novel Neural Circuit Biomarkers of Major Depression Response to Computer-augmented CBT
- ClinicalTrials.gov ID
- NCT03096886
- Acronym / sponsor ID
- R01MH110939-01A1
- Keywords
- Cognitive Behavioral Therapy, Computer-Assisted Cognitive Behavioral Therapy, Computer-Augmented Cognitive Behavioral Therapy, CBT, Computer-Assisted CBT, Computer-Augmented CBT
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 132 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- 5 Jun 2017 (actual)
- Primary completion
- 23 Oct 2023 (actual)
- Study completion
- 23 Oct 2023 (actual)
- First posted
- 30 Mar 2017 (actual)
- Results
- Posted 5 Dec 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This study is a randomized study. 80 subjects with MDD will be randomly assigned (1:1) to immediately receive 8 weeks of CCBT or delayed treatment, consisting of up to 4 weeks of waitlist, followed by 8 weeks of CCBT. 50 healthy controls of similar age/sex will be recruited to serve as a comparison group for baseline magnetic resonance imaging (MRI) scanning.
The study will enroll subjects for approximately 4 years (~2 subjects per month for 48 months). The length of subject participation will vary based on what group the participants are randomized to. Healthy controls will participate for approximately 8 weeks. Subjects with MDD who were randomized to Early CCBT will participate for approximately 8 weeks; subjects with MDD who were randomized to Late CCBT will participate for approximately 12 weeks. Variability in the study duration for each group depends on each subjects' personal availability for visits and the availability of the magnetic resonance scanner.
Potential participants will complete a phone screen to determine eligibility. If the individual is eligible, the individual will be scheduled for an in-person screening visit. Information collected during the phone screening will not be used in the data analysis; phone screening information will be collected and retained in REDCap. Remote contact options are available as needed/possible.
Screening Visit - all participants will have the study described to them in detail, including the risks and study procedures as outlined in the informed consent form and will sign the informed consent form (ICF) and HIPAA authorization, prior to any study procedures being completed. Participants will be screened for symptoms of psychological disorders and severity of major depressive symptoms by a trained research team member.
If determined eligible, HEALTHY CONTROLS will be scheduled for return to complete an fMRI scan and baseline visit, in which self-report measures, including reports of mood, behavior, and thoughts will be collected, as well as neuropsychological testing. The HIPAA-compliant phone app Beiwe and actigraph setup will take place during the baseline visit. Participants will complete mood monitoring questions on the phone app and also have their activity levels monitored by the phone app and the actigraph for the duration of the study.
If determined eligible at screening, MDD (EXPERIMENTAL GROUP) participants will be randomized (1:1) as follows: One half of the depressed participants will be randomized to receive 8 weeks of CCBT immediately after completing pretreatment assessments and the remainder will be randomized to a waitlist of up to 4 weeks followed by 8 weeks of CCBT.
MDD, EARLY CCBT GROUP Early CCBT participants will be scheduled for return to complete an fMRI scan at the baseline visit, in which self-report measures, including reports of mood, behavior, and thoughts will be collected, as well as neuropsychological testing. The phone apps Beiwe and Ethica and actigraph setup will take place during the baseline visit. Participants will complete mood monitoring questions on the phone apps and also have their activity levels monitored by the phone app and the actigraph for the duration of the study. Participants will complete Good Days Ahead (GDA) computer training throughout the 8 weeks of CCBT, and having 6 encounters with a licensed psychologist/psychiatrist. Additionally, outcome measures will be assessed by an independent clinical evaluator (without knowledge of treatment assignment) every other week. As soon as can be arranged after Week 9 of CCBT treatment (last CCBT Clinical Contact), participants will return to complete an fMRI scan and end of study visit, in which self-report measures, including reports of mood, behavior, and thoughts will be collected, as well as neuropsychological testing.
MDD, LATE CCBT GROUP Late CCBT participants will be scheduled for return to complete an fMRI scan and baseline visit, in which self-report measures, including reports of mood, behavior, and thoughts will be collected, as well as neuropsychological testing. The phone apps Beiwe and Ethica and actigraph setup will take place during the baseline visit. During the 2-4 week waitlist phase, participants will complete mood monitoring questions on the phone apps and also have their activity levels monitored by the phone app and the actigraph.
At the conclusion of the waitlist of up to 4 weeks, participants will complete a second fMRI scan and complete self-report measures, including reports of mood, behavior, and thoughts will be collected, as well as neuropsychological testing.
Participants will then enter the CCBT phase and will complete Good Days Ahead (GDA) computer training throughout the 8 weeks of CCBT. They will have 6 encounters with a licensed psychologist/psychiatrist at multiple time points during this period. Additionally, outcome measures will be assessed by an independent clinical evaluator (without knowledge of treatment assignment) every other week during this study phase. At Week 9 of CCBT treatment (last CCBT Clinical Contact), participants will complete a 1-hour fMRI scan and self-report measures, including reports of mood, behavior, and thoughts will be collected, as well as neuropsychological testing.
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 130 subjects for this clinical trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 3
- Model description
- 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).
| Arm | Type | Receives |
|---|---|---|
| Early CCBT | Experimental | Behavioral: Computer-Augmented Cognitive Behavioral TherapyIntervention: 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. |
| Late CCBT | Experimental | Behavioral: Computer-Augmented Cognitive Behavioral TherapyIntervention: 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. |
| Matched Comparison | No intervention | –No Intervention: Matched Comparison Healthy controls will act as a matched comparator. Participants will complete pre-treatment assessments and imaging. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (12 listed)
- 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
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 |
|---|---|---|
| Computer-Augmented Cognitive Behavioral TherapyAlso: CCBT, Computer-Assisted Cognitive Behavioral TherapyThe 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. | Behavioural | Early CCBT, Late CCBT |
Primary outcome
Resting State Functional Connectivity: MDD vs Controls
Time frame: Baseline
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.
1 secondary outcome
Resting State Functional Connectivity: Immediate CCBT vs Waitlist Followed by CCBT
Time frame: Week 8
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 28275546Shou 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.
- Background: PubMed 21130939Newman 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.
- Background: PubMed 19309197Vittengl 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.
- Background: PubMed 25553400Biesheuvel-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.
- Background: PubMed 8561380Seligman 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.
- Background: PubMed 20183695Andersson 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.
- Background: PubMed 15930065Wright 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.
- Background: PubMed 24059735Eells 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.
- Background: PubMed 24690111Korgaonkar 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.
- Background: PubMed 9276848Mayberg 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.
- Background: PubMed 18704495Drevets 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.
- Background: PubMed 11704071Sheline 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.
- Individual participant dataSharing planned: Undecided
Related trials for Depression
Recruiting
Unified Protocol in Penitentiary Facilities
Depression Disorders, Anxiety
Not yet recruiting
Preventive and Personalized Digital Emotion Regulation Skills Intervention to Reduce Depression and Anxiety in Youths With Adverse Childhood Experiences
Adverse Childhood Experience, Depression / Major Depressive Disorder
Not yet recruitingObservational study
Functional Impact of Psychological Symptoms in Patients With Superior Semicircular Canal Dehiscence Syndrome (SSCD): a National Cross-sectional Study
Superior Semicircular Canal Dehiscence
Recruiting
Trial Phase: Syndemic Adapted Medly Uganda
Mental Health
Recruiting
Cultural Adaptation of an Online Parenting Intervention to Reduce the Risk of Depression and Anxiety in Adolescents
Risk of Depression and Anxiety
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.
Yvette I Sheline, MD principal investigator
University of Pennsylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Computer-Augmented Cognitive Behavioral Therapy in people with Depression and Major Depressive Disorder, run by University of Pennsylvania 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?
The sponsor lists 8 inclusion and 12 exclusion criteria. 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 5 Dec 2024. 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?
Yes. Results are posted in the registry (first posted 5 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Resting State Functional Connectivity: MDD vs Controls (time frame: Baseline). 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 NCT03096886, which also lists 19 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 5 Dec 2024.