Major Depressive Disorder (MDD)NCT07091643
Neuroimaging Markers of Midlife Depression and Cognitive Behavioural Therapy (CBT)
A study testing Cognitive Behavioural Therapy in people with Major Depressive Disorder (MDD), run by Baycrest at 1 site in Canada.
Trial summary
Major depressive disorder (MDD) is associated with significant cognitive impairment throughout the life-course, which may progress toward MCI and dementia with age. Antidepressant medications are the first line of treatment; however, they fail to adequately address cognitive deficits and prevent relapse. Read more about this study
- Who is it for?
- Ages 40 to 60 years
- Conditions the study is for
- Major Depressive Disorder (MDD)
- What is being tested?
- Cognitive Behavioural Therapy
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteCanada
- Study dates
- Jun 2026to Dec 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 40 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Age 40-60 years, inclusive.
- Diagnosis of MDD as per the Diagnostic and Statistical Manual of Mental Disorders (DSM-5)6 determined through a structured clinical interview.
- Current major depressive episode of at least 3 months in length.
- Depression of at least mild severity defined by a total score of ≥7 on the Montgomery Asberg Depression Rating Scale (MADRS)7.
- Ability to understand and comply with the requirements of the study, as judged by the investigator(s).
Who cannot join
- Presence of comorbid post-traumatic stress disorder, obsessive-compulsive disorder, eating disorder(s), schizophrenia, or other psychiatric disorders.
- History of a manic, hypomanic, or mixed depressive episode.
- Treatment with electroconvulsive therapy, intravenous and/or intranasal ketamine in the 6-weeks prior to study enrolment.
- History of substance-use disorder in the past 12 months.
- Presence of current alcohol-use disorder
- A positive urine toxicology screen for non-prescribed substance use.
Show all 10Show fewer
- A positive pregnancy test at screening.
- A history of major medical or neurological illness.
- A history of traumatic brain injury, stroke, seizures, or previous brain surgery.
- Contraindications to magnetic resonance imaging (MRI) scanning.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site
Baycrest Hospital
Toronto, Ontario, M6A 2E1
Principal Investigator, 416-785-2500 ext. 2017, jean.chen@utoronto.ca
About this study
Major depressive disorder (MDD) is associated with significant cognitive impairment throughout the life-course, which may progress toward MCI and dementia with age. Antidepressant medications are the first line of treatment; however, they fail to adequately address cognitive deficits and prevent relapse. Sustained cognitive impairment into euthymic periods may relate to underlying neurobiological changes, which could potentially be addressed through Cognitive Behavioural Therapy (CBT). Notably, CBT has been shown to improve cognitive domains including divided attention, memory, and processing speed while preventing depression relapse. Midlife represents a critical period in which shared neurobiological factors (such as brain changes on a vascular, morphological, and functional level) underlying depression and cognitive impairment could accelerate toward MCI and dementia. An updated understanding of neurobiological correlates of midlife depression and CBT response through multimodal neuroimaging is critical to improving affective and cognitive outcomes in this population.
The overarching objective of this project is to use multimodal neuroimaging to quantify the neurobiological and clinical impact of CBT in midlife depression. Specifically, we aim to:
Read more
- Investigate the clinical impact of CBT on cognitive function and mood outcomes in midlife depression
- Examine functional connectivity and microstructural determinants of CBT response in midlife depression using neuroimaging
- Identify vascular modulators of neural connectivity and CBT response in midlife depression.
We hypothesize that midlife depression will be associated with functional and structural neural connectivity changes, which will be accompanied by vascular pathology. Adequate CBT response (i.e., improvements in mood and cognitive function) will be associated with amelioration of neurobiological changes.
- Conditions
- Major Depressive Disorder (MDD)
- Being tested
- Cognitive Behavioural Therapy
- Keywords
- Midlife Depression, Depression, Cognitive Behavioural Therapy (CBT)
- Medical subject headings
- Depressive Disorder, Major, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cognitive Behavioural TherapyBehavioural
12 weeks of Cognitive Behavioural Therapy (CBT) will be administered. The first session will be accomplished in-person at Baycrest Hospital. After that, therapy will be conducted virtually, via video-conference. Individuals will undergo therapy once a week for approximately 1 hour, for 12-weeks. Following the 12-week period, individuals will receive three follow-up assessments with their therapist at 3, 6, and 9 months.
| Study group | Role | What they receive |
|---|---|---|
| Experimental Group | Experimental | Individuals with midlife depression (MDD, ages 40-60 years) will undergo 12 weeks of CBT, in addition to three follow-up assessments, clinical evaluation (including completion of self-report and clinician-rated questionnaires) and pre-post CBT magnetic resonance imaging (MRI). Receives: Behavioral: Cognitive Behavioural Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
MADRS
The Montgomery-Åsberg Depression Rating Scale (MADRS) is a clinician-rated scale used to assess the severity of depressive symptoms. It is a 10-item scale, with each item rated on a 7-point scale, and the total score ranges from 0 to 60, with higher scores indicating more severe depression. The MADRS is commonly used in clinical trials and research to evaluate treatment response in individuals with depression.
Measured: Once before administration of Cognitive Behavioural Therapy (CBT) and once after (baseline and 12 weeks).
DARS
The Dimensional Anhedonia Rating Scale (DARS) is a 17-item self-report scale used to assess anhedonia, a core symptom of depression characterized by a reduced ability to experience pleasure. It measures anhedonia across four domains: hobbies, food/drink, social activities, and sensory experiences, evaluating aspects like desire, motivation, effort, and consummatory pleasure.
Measured: Once before administration of Cognitive Behavioural Therapy (CBT) and once after (baseline and 12 weeks).
Secondary outcomes (3)
T1-anatomical
A T1 anatomical MRI, also known as a T1-weighted MRI, is a type of magnetic resonance imaging (MRI) sequence that excels at visualizing the structural details of tissues, particularly soft tissues and fat. It's often used to provide a clear view of the b
Measured: Once before administration of Cognitive Behavioural Therapy (CBT) and once after (baseline and 12 weeks).
Diffusion-tensor MRI
Diffusion tensor MRI (DTI) is an advanced magnetic resonance imaging (MRI) technique that maps the diffusion of water molecules in the brain to visualize the white matter pathways. It provides insights into the structural organization and integrity of white matter, which is crucial for understanding brain connectivity and function.
Measured: Once before administration of Cognitive Behavioural Therapy (CBT) and once after (baseline and 12 weeks).
Resting-state fMRI
Resting state fMRI (rs-fMRI) is a technique used to study brain activity when a person is not performing a specific task. It focuses on spontaneous fluctuations in the blood-oxygen-level-dependent (BOLD) signal to identify functional connections between different brain regions. We will use this signal to compute functional connectivity
Measured: Once before administration of Cognitive Behavioural Therapy (CBT) and once after (baseline and 12 weeks).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2025
- Study startJun 2026 (estimated)
- Primary completionDec 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Major Depressive Disorder (MDD)Studies of the same condition, open and under way.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Baycrest
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jean Chen, Baycrest
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07091643
- Sponsor's protocol ID
- REB 22-10
- Status last verified
- Jul 2025
- First submitted
- 22 Jul 2025
- Last updated
- 27 Feb 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
World Health Organization. Division of Mental Health and Prevention of Substance Abuse. (1997). WHOQOL : measuring quality of life. World Health Organization.
Leach, L., Kaplan, E., Rewilak, D., Richards, B., & Proulx, G. (2000). The Kaplan-Baycrest neurocognitive assessment (KBNA): Test manual. San Antonio, TX, Harcourt Assessment.
Soares CN. Mood disorders in midlife women: understanding the critical window and its clinical implications. Menopause. 2014 Feb;21(2):198-206. doi: 10.1097/GME.0000000000000193.
PubMed 24448106Perini G, Cotta Ramusino M, Sinforiani E, Bernini S, Petrachi R, Costa A. Cognitive impairment in depression: recent advances and novel treatments. Neuropsychiatr Dis Treat. 2019 May 10;15:1249-1258. doi: 10.2147/NDT.S199746. eCollection 2019.
PubMed 31190831Brenowitz WD, Zeki Al Hazzouri A, Vittinghoff E, Golden SH, Fitzpatrick AL, Yaffe K. Depressive Symptoms Imputed Across the Life Course Are Associated with Cognitive Impairment and Cognitive Decline. J Alzheimers Dis. 2021;83(3):1379-1389. doi: 10.3233/JAD-210588.
PubMed 34420969
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neuroimaging Markers of Midlife Depression and Cognitive Behavioural Therapy (CBT)
- ClinicalTrials.gov ID
- NCT07091643
- Acronym / sponsor ID
- REB 22-10
- Conditions
- Major Depressive Disorder (MDD)
- Keywords
- Midlife Depression, Depression, Cognitive Behavioural Therapy (CBT)
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- BaycrestUniversity, hospital or other
- Study start
- Jun 2026 (estimated)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 29 Jul 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Major depressive disorder (MDD) is associated with significant cognitive impairment throughout the life-course, which may progress toward MCI and dementia with age. Antidepressant medications are the first line of treatment; however, they fail to adequately address cognitive deficits and prevent relapse. Sustained cognitive impairment into euthymic periods may relate to underlying neurobiological changes, which could potentially be addressed through Cognitive Behavioural Therapy (CBT). Notably, CBT has been shown to improve cognitive domains including divided attention, memory, and processing speed while preventing depression relapse. Midlife represents a critical period in which shared neurobiological factors (such as brain changes on a vascular, morphological, and functional level) underlying depression and cognitive impairment could accelerate toward MCI and dementia. An updated understanding of neurobiological correlates of midlife depression and CBT response through multimodal neuroimaging is critical to improving affective and cognitive outcomes in this population.
The overarching objective of this project is to use multimodal neuroimaging to quantify the neurobiological and clinical impact of CBT in midlife depression. Specifically, we aim to:
- Investigate the clinical impact of CBT on cognitive function and mood outcomes in midlife depression
- Examine functional connectivity and microstructural determinants of CBT response in midlife depression using neuroimaging
- Identify vascular modulators of neural connectivity and CBT response in midlife depression.
We hypothesize that midlife depression will be associated with functional and structural neural connectivity changes, which will be accompanied by vascular pathology. Adequate CBT response (i.e., improvements in mood and cognitive function) will be associated with amelioration of neurobiological changes.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental Group | Experimental | Behavioral: Cognitive Behavioural TherapyIndividuals with midlife depression (MDD, ages 40-60 years) will undergo 12 weeks of CBT, in addition to three follow-up assessments, clinical evaluation (including completion of self-report and clinician-rated questionnaires) and pre-post CBT magnetic resonance imaging (MRI). |
Who may qualify
- Ages
- 40 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Age 40-60 years, inclusive.
- Diagnosis of MDD as per the Diagnostic and Statistical Manual of Mental Disorders (DSM-5)6 determined through a structured clinical interview.
- Current major depressive episode of at least 3 months in length.
- Depression of at least mild severity defined by a total score of ≥7 on the Montgomery Asberg Depression Rating Scale (MADRS)7.
- Ability to understand and comply with the requirements of the study, as judged by the investigator(s).
Key exclusion criteria (10 listed)
- Presence of comorbid post-traumatic stress disorder, obsessive-compulsive disorder, eating disorder(s), schizophrenia, or other psychiatric disorders.
- History of a manic, hypomanic, or mixed depressive episode.
- Treatment with electroconvulsive therapy, intravenous and/or intranasal ketamine in the 6-weeks prior to study enrolment.
- History of substance-use disorder in the past 12 months.
- Presence of current alcohol-use disorder
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 |
|---|---|---|
| Cognitive Behavioural Therapy12 weeks of Cognitive Behavioural Therapy (CBT) will be administered. The first session will be accomplished in-person at Baycrest Hospital. After that, therapy will be conducted virtually, via video-conference. Individuals will undergo therapy once a week for approximately 1 hour, for 12-weeks. Following the 12-week period, individuals will receive three follow-up assessments with their therapist at 3, 6, and 9 months. | Behavioural | Experimental Group |
Primary outcome
MADRS
Time frame: Once before administration of Cognitive Behavioural Therapy (CBT) and once after (baseline and 12 weeks).
The Montgomery-Åsberg Depression Rating Scale (MADRS) is a clinician-rated scale used to assess the severity of depressive symptoms. It is a 10-item scale, with each item rated on a 7-point scale, and the total score ranges from 0 to 60, with higher scores indicating more severe depression. The MADRS is commonly used in clinical trials and research to evaluate treatment response in individuals with depression.
DARS
Time frame: Once before administration of Cognitive Behavioural Therapy (CBT) and once after (baseline and 12 weeks).
The Dimensional Anhedonia Rating Scale (DARS) is a 17-item self-report scale used to assess anhedonia, a core symptom of depression characterized by a reduced ability to experience pleasure. It measures anhedonia across four domains: hobbies, food/drink, social activities, and sensory experiences, evaluating aspects like desire, motivation, effort, and consummatory pleasure.
3 secondary outcomes
T1-anatomical
Time frame: Once before administration of Cognitive Behavioural Therapy (CBT) and once after (baseline and 12 weeks).
Diffusion-tensor MRI
Time frame: Once before administration of Cognitive Behavioural Therapy (CBT) and once after (baseline and 12 weeks).
Resting-state fMRI
Time frame: Once before administration of Cognitive Behavioural Therapy (CBT) and once after (baseline and 12 weeks).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2026.
- BackgroundWorld Health Organization. Division of Mental Health and Prevention of Substance Abuse. (1997). WHOQOL : measuring quality of life. World Health Organization.
- BackgroundLeach, L., Kaplan, E., Rewilak, D., Richards, B., & Proulx, G. (2000). The Kaplan-Baycrest neurocognitive assessment (KBNA): Test manual. San Antonio, TX, Harcourt Assessment.
- Background: PubMed 24448106Soares CN. Mood disorders in midlife women: understanding the critical window and its clinical implications. Menopause. 2014 Feb;21(2):198-206. doi: 10.1097/GME.0000000000000193.
- Background: PubMed 31190831Perini G, Cotta Ramusino M, Sinforiani E, Bernini S, Petrachi R, Costa A. Cognitive impairment in depression: recent advances and novel treatments. Neuropsychiatr Dis Treat. 2019 May 10;15:1249-1258. doi: 10.2147/NDT.S199746. eCollection 2019.
- Background: PubMed 34420969Brenowitz WD, Zeki Al Hazzouri A, Vittinghoff E, Golden SH, Fitzpatrick AL, Yaffe K. Depressive Symptoms Imputed Across the Life Course Are Associated with Cognitive Impairment and Cognitive Decline. J Alzheimers Dis. 2021;83(3):1379-1389. doi: 10.3233/JAD-210588.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cognitive Behavioural Therapy in people with Major Depressive Disorder (MDD), run by Baycrest at 1 site in Canada.
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 5 inclusion and 10 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: opening soon, as of the sponsor's last update on 27 Feb 2026. 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 Canada. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Principal Investigator (416-785-2500 ext. 2017, jean.chen@utoronto.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
MADRS (time frame: Once before administration of Cognitive Behavioural Therapy (CBT) and once after (baseline and 12 weeks).). The study lists 2 primary outcomes in all. 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 NCT07091643, which also lists 5 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 27 Feb 2026.