Major Depressive DisorderPhase 4NBOLDNCT05273996
Predictors of Cognitive Outcomes in Geriatric Depression
A Phase 4 study testing Sertraline, bupropion, desvenlafaxine in people with Major Depressive Disorder and Neuroticism, run by David Steffens at 1 site in United States.
Trial summary
This study will focus on examining effects of stress on long-term mood and cognitive outcomes of late-life depression. It will also example the neural underpinnings of these changes using structural and functional brain imaging. Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Major Depressive Disorder, Neuroticism, Cognitive Change
- What is being tested?
- Sertraline, bupropion, desvenlafaxine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 75 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Sep 2021to 30 Apr 2027
- Phase
- Phase 4
- 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 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- major depression, single episode or recurrent;
- ability to read and write English;
- Mini-Mental State Examination >25.
Who cannot join
- lifetime alcohol/drug dependence
- conditions associated with brain abnormalities such hydrocephalus, benign and cancerous brain tumors, epilepsy, Parkinson's disease, Huntington's chorea, dementia, demyelinating diseases, etc.
- untreated endocrine disorder other than diabetes mellitus
- established clinical diagnosis of dementia
- other primary psychiatric disorders, e.g., panic disorder, social phobia, obsessive- compulsive disorder, schizoaffective disorder, schizophrenia, bipolar disorder
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phenotype Predictors of Cognitive Outcomes in Geriatric Depression
This study will focus on examining effects of stress on long-term mood and cognitive outcomes of late-life depression. It will also example the neural underpinnings of these changes using structural and functional brain imaging. Understanding how effects of stress in older depressed adults, as well as factors that might minimize those effects, lead to particular mood and cognitive outcomes will inform future development of novel prevention strategies.
Read the detailed description
In this renewal of R01MH108578, the investigators are seeking to extend findings from the initial study to focus on effects of stress in longitudinal mood and cognitive outcomes of late-life depression (LLD) and to examine stress effects on brain structure and function in LLD. Severe or persistent stressors can result in a number of behavioral and mood changes, including anxiety, dysphoric mood, sleep disruption, altered appetite, and withdrawal from social and pleasurable activities. These stress-related consequences are particularly salient when considering longitudinal outcomes of treated LLD. They may be compounded by an individual's longstanding maladaptive patterns of response to stress, embodied in the construct of neuroticism, which the investigators have shown to be related to poor mood and cognitive LLD outcomes. Moreover, Andreescu et al. (2019) introduced a model of depression recurrence that incorporates the homeostatic disequilibrium hypothesis, which proposes that in geriatric remitted depression, neural networks are in fragile homeostasis that is threatened by stress exposure. Networks of particular importance in stress of LLD outcome are the Default Mode Network (DMN), Salience Network (SN) and Executive Control Network (ECN).
The Neurobiology of Late Life Depression (NBOLD) study began enrolling older depressed and never depressed controls in 2013, enrolling 132 depressed and 44 controls, and currently follows 77 depressed and 22 controls. Subjects are well characterized in terms of mood, cognition, personality and stress (including specific measures obtained during the present COVID pandemic). It is well suited to examine stress effects on longitudinal mood and cognitive outcomes. For the renewal, the study will follow current subjects and recruit 75 new subjects, who will be followed for up to 5 years with annual cognitive testing, stress measures and baseline and two-year functional brain magnetic resonance imaging (fMRI) scan.
In this renewal, the investigators will examine the following specific aims:
- To study effects of stressors (obtained on a variety of measures) and neuroticism on longitudinal mood and cognitive outcomes in older adults with history of major depressive disorder (MDD).
- To study effects of stress and neuroticism on brain structure and function in older adults with MDD history.
- To explore relationships among variables in Aims 1 and 2 with longitudinal multivariable statistical models.
- Conditions
- Major Depressive Disorder, Neuroticism, Cognitive Change, Stress
- Being tested
- Sertraline, bupropion, desvenlafaxine
- Keywords
- Late Life Depression
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sertraline, bupropion, desvenlafaxineDrug
Also called Zoloft, Wellbutrin, Pristiq
Study geriatric psychiatrists prescribe FDA-approved antidepressants using a treatment algorithm consistent with the STAGED (Duke Somatic Treatment Algorithm for Geriatric Depression) approach, with standardization of treatment in the first six months beginning with sertraline, with the option of augmentation with bupropion or switch to desvenlafaxine. Beyond six months of acute treatment, subjects are treated based on the study psychiatrist's clinical assessment and recommendations, consistent with STAGED guidelines.
| Study group | Role | What they receive |
|---|---|---|
| Depressed | Other | Subjects receive FDA-approved antidepressants Receives: Drug: Sertraline, bupropion, desvenlafaxine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Montgomery-Asberg Depression Rating Scale (MADRAS)
Measure of depression severity and Recurrence of Depression Minimum Score = 0; Maximum Score = 60; Higher score means worse outcome
Measured: Three years
Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Neuropsychological Battery Total Score
Global cognitive measure; Minimum Score = 0; Maximum Score = 100; Higher score means better outcome
Measured: Three years
Cognitive clinical diagnosis
Participant records will be reviewed annually by the consensus panel. The study will convene a panel of experts to review each case, including the PI, treating geriatric psychiatrists and study neuropsychologist. Panel members review the following information for each participant: 1) initial evaluation and most recent clinical depression study notes, 2) neuropsychological testing profiles, 3) informant report of cognitive decline based on the Dementia Severity Rating Scale, 4) study structural MRI images to determine vascular burden, and 5) additional neurological and clinical neuropsychological consultations when available. The panel discusses the case until a consensus cognitive diagnosis is reached.
Measured: three years
Secondary outcomes (2)
Functional brain magnetic resonance imaging (fMRI) scan changes in resting state functional connectivity.
A change in the strength of connectivity within a network and between two networks will be determined by comparing the strength of connectivity at baseline and at two years. The functional connectivity strength is reflected by a z score of normalized Pearson correlation coefficient using the Fisher transformation.
Measured: Two years
Functional brain magnetic resonance imaging (fMRI) scan structural imaging changes
Measures from structural imaging in the key brain regions will be the volumetric measurement from T1-weighted MRI. A change in the volume of a brain structure will be determined by subtracting the regional volume at baseline from two years.
Measured: Two years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2022
- Study start28 Sep 2021
- Primary completion30 Apr 2027 (estimated)
- Study completion30 Apr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depressive DisorderStudies 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 4
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Naturalistic study using FDA approved antidepressants to examine the effects of stress and neuroticism on outcomes
- Masking
- None (open label)
- Enrolment
- 75 participants (estimated)
Sponsor and investigators
- Lead sponsor
- David Steffens
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor-investigator, David Steffens, UConn Health
- Investigators
- David Steffens, M.D., M.H.S., Principal investigator, UConn Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05273996
- Sponsor's protocol ID
- IE-13-048H-6.1
- Other IDs
- R01MH108578
- Acronym
- NBOLD
- Status last verified
- May 2026
- First submitted
- 13 Dec 2021
- Last updated
- 22 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: This R01 will develop important new data on 75 subjects. These data will be available to investigators both within UConn and outside the institution.
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phenotype Predictors of Cognitive Outcomes in Geriatric Depression
- ClinicalTrials.gov ID
- NCT05273996
- Acronym / sponsor ID
- NBOLD / IE-13-048H-6.1
- Conditions
- Major Depressive Disorder, Neuroticism, Cognitive Change, Stress
- Keywords
- Late Life Depression
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 75 participants (estimated)
- Lead sponsor
- David SteffensUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 28 Sep 2021 (actual)
- Primary completion
- 30 Apr 2027 (estimated)
- Study completion
- 30 Apr 2027 (estimated)
- First posted
- 10 Mar 2022 (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.
This study will focus on examining effects of stress on long-term mood and cognitive outcomes of late-life depression. It will also example the neural underpinnings of these changes using structural and functional brain imaging. Understanding how effects of stress in older depressed adults, as well as factors that might minimize those effects, lead to particular mood and cognitive outcomes will inform future development of novel prevention strategies.
Detailed description
In this renewal of R01MH108578, the investigators are seeking to extend findings from the initial study to focus on effects of stress in longitudinal mood and cognitive outcomes of late-life depression (LLD) and to examine stress effects on brain structure and function in LLD. Severe or persistent stressors can result in a number of behavioral and mood changes, including anxiety, dysphoric mood, sleep disruption, altered appetite, and withdrawal from social and pleasurable activities. These stress-related consequences are particularly salient when considering longitudinal outcomes of treated LLD. They may be compounded by an individual's longstanding maladaptive patterns of response to stress, embodied in the construct of neuroticism, which the investigators have shown to be related to poor mood and cognitive LLD outcomes. Moreover, Andreescu et al. (2019) introduced a model of depression recurrence that incorporates the homeostatic disequilibrium hypothesis, which proposes that in geriatric remitted depression, neural networks are in fragile homeostasis that is threatened by stress exposure. Networks of particular importance in stress of LLD outcome are the Default Mode Network (DMN), Salience Network (SN) and Executive Control Network (ECN).
The Neurobiology of Late Life Depression (NBOLD) study began enrolling older depressed and never depressed controls in 2013, enrolling 132 depressed and 44 controls, and currently follows 77 depressed and 22 controls. Subjects are well characterized in terms of mood, cognition, personality and stress (including specific measures obtained during the present COVID pandemic). It is well suited to examine stress effects on longitudinal mood and cognitive outcomes. For the renewal, the study will follow current subjects and recruit 75 new subjects, who will be followed for up to 5 years with annual cognitive testing, stress measures and baseline and two-year functional brain magnetic resonance imaging (fMRI) scan.
In this renewal, the investigators will examine the following specific aims:
- To study effects of stressors (obtained on a variety of measures) and neuroticism on longitudinal mood and cognitive outcomes in older adults with history of major depressive disorder (MDD).
- To study effects of stress and neuroticism on brain structure and function in older adults with MDD history.
- To explore relationships among variables in Aims 1 and 2 with longitudinal multivariable statistical models.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Naturalistic study using FDA approved antidepressants to examine the effects of stress and neuroticism on outcomes
| Arm | Type | Receives |
|---|---|---|
| Depressed | Other | Drug: Sertraline, bupropion, desvenlafaxineSubjects receive FDA-approved antidepressants |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (3 listed)
- major depression, single episode or recurrent;
- ability to read and write English;
- Mini-Mental State Examination >25.
Key exclusion criteria (5 listed)
- lifetime alcohol/drug dependence
- conditions associated with brain abnormalities such hydrocephalus, benign and cancerous brain tumors, epilepsy, Parkinson's disease, Huntington's chorea, dementia, demyelinating diseases, etc.
- untreated endocrine disorder other than diabetes mellitus
- established clinical diagnosis of dementia
- other primary psychiatric disorders, e.g., panic disorder, social phobia, obsessive- compulsive disorder, schizoaffective disorder, schizophrenia, bipolar 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 |
|---|---|---|
| Sertraline, bupropion, desvenlafaxineAlso: Zoloft, Wellbutrin, PristiqStudy geriatric psychiatrists prescribe FDA-approved antidepressants using a treatment algorithm consistent with the STAGED (Duke Somatic Treatment Algorithm for Geriatric Depression) approach, with standardization of treatment in the first six months beginning with sertraline, with the option of augmentation with bupropion or switch to desvenlafaxine. Beyond six months of acute treatment, subjects are treated based on the study psychiatrist's clinical assessment and recommendations, consistent with STAGED guidelines. | Drug | Depressed |
Primary outcome
Montgomery-Asberg Depression Rating Scale (MADRAS)
Time frame: Three years
Measure of depression severity and Recurrence of Depression Minimum Score = 0; Maximum Score = 60; Higher score means worse outcome
Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Neuropsychological Battery Total Score
Time frame: Three years
Global cognitive measure; Minimum Score = 0; Maximum Score = 100; Higher score means better outcome
Cognitive clinical diagnosis
Time frame: three years
Participant records will be reviewed annually by the consensus panel. The study will convene a panel of experts to review each case, including the PI, treating geriatric psychiatrists and study neuropsychologist. Panel members review the following information for each participant: 1) initial evaluation and most recent clinical depression study notes, 2) neuropsychological testing profiles, 3) informant report of cognitive decline based on the Dementia Severity Rating Scale, 4) study structural MRI images to determine vascular burden, and 5) additional neurological and clinical neuropsychological consultations when available. The panel discusses the case until a consensus cognitive diagnosis is reached.
2 secondary outcomes
Functional brain magnetic resonance imaging (fMRI) scan changes in resting state functional connectivity.
Time frame: Two years
Functional brain magnetic resonance imaging (fMRI) scan structural imaging changes
Time frame: Two years
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 22 May 2026.
- Individual participant dataSharing planned: Yes. This R01 will develop important new data on 75 subjects. These data will be available to investigators both within UConn and outside the institution.
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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. This study is not recruiting at the moment.
David Steffens, M.D., M.H.S. principal investigator
UConn Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Sertraline, bupropion, desvenlafaxine in people with Major Depressive Disorder and Neuroticism, run by David Steffens 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 3 inclusion and 5 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: under way, not looking for participants, as of the sponsor's last update on 22 May 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 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
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?
Montgomery-Asberg Depression Rating Scale (MADRAS) (time frame: Three years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 22 May 2026.