Major Depressive DisorderPhase 4NCT01896934
Frontal Hypoperfusion Effects on Antidepressant Outcomes in Late-Life Depression
A Phase 4 study testing Sertraline in people with Major Depressive Disorder, run by Vanderbilt University at 1 site in United States.
Trial summary
The long-term goal of this line of research is to determine if decreased vascular reactivity and frontal hypoperfusion is associated with poor response antidepressants. Such perfusion deficits could contribute to antidepressant nonresponse as they would hinder improvements in dorsal system metabolism seen with… Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- Sertraline
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2013to Jun 2016
- Phase
- Phase 4
- 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 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 60 years or older.
- Current diagnosis of major depressive disorder (DSM-IV-TR), single episode, recurrent or chronic, without psychotic features, as detected by MINI and clinical exam.
- Minimum MADRS score ≥ 15.
- Mini-Mental State Exam ≥ 22.
- Ability to read and write English.
Who cannot join
- Current or past diagnoses of other Axis I psychiatric disorders, including panic disorder and substance dependence.
- Any use of illicit substances (such as marijuana or cocaine) or abuse of prescription medications (such as benzodiazepines or opiates) within the last three months.
- Presence of acute suicidality
- Current or past psychosis
- Known primary neurological disorder, including dementia, brain tumors, epilepsy, Parkinson's disease, or demyelinating diseases
- Chronic untreated medical disorders (including but not limited to hypertension, hyperlipidemia, fibromyalgia, hypothyroidism, or any other disorder) where treatment is warranted
Show all 14Show fewer
- Need for continuous oxygen use or any medical disorder where the hypercapnia challenge would be contraindicated or put the subject at increased risk. This would include active respiratory disease, chronic angina or other unstable cardiac conditions.
- Any physical or intellectual disability affecting completion of assessments
- MRI contraindications
- Electroconvulsive therapy in last 6 months
- Use of fluoxetine in the last 6 weeks. Occasional use of benzodiazepines or non-benzodiazepine sedatives (such as zolpidem, eszopiclone, or zaleplon) during the last month is allowable.
- Known allergy or hypersensitivity to sertraline
- A failed therapeutic trial of sertraline in the current depressive episode (defined as at least 6 weeks of treatment at a daily dose of 100mg or higher)
- Current or planned psychotherapy
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Frontal Hypoperfusion Effects on Antidepressant Outcomes in Late-Life Depression (R21)
The long-term goal of this line of research is to determine if decreased vascular reactivity and frontal hypoperfusion is associated with poor response antidepressants. Such perfusion deficits could contribute to antidepressant nonresponse as they would hinder improvements in dorsal system metabolism seen with antidepressant treatment. The objective of the current proposal is to determine if decreased vascular reactivity and frontal hypoperfusion in depressed elders predicts and persists with antidepressant nonremission. The investigators will pursue the primary aim testing the hypothesis that decreased reactivity and hypoperfusion, specifically in the dorsolateral prefrontal cortex and dorsal anterior cingulate cortex, predict antidepressant nonremission. The investigators will enroll 40 depressed elders who will complete clinical, cognitive, and MRI assessments before and after a 12-week open-label antidepressant trial of sertraline.
Read the detailed description
The long-term goal of this line of research is to determine if in late-life depression (LLD), cerebrovascular dysregulation is predictive of antidepressant outcomes. The investigators hypothesize that vascular pathology resulting in reduced cerebrovascular reactivity contributes to frontocingulate hypoperfusion. Such pathology would impair neurovascular coupling and reduce the ability of the vasculature to improve frontocingulate perfusion during antidepressant treatment. Thus decreased cerebrovascular reactivity and perfusion may be a biomarker of antidepressant nonresponse. As an initial step in this research, the current study will utilize MRI arterial spin labeling (ASL) to examine if cerebrovascular reactivity deficits and resting cerebral blood flow (CBF) deficits predict antidepressant nonremission in LLD. The rationale for this proposal is that it will identify mechanisms by which vascular pathology may contribute to LLD. If the study hypotheses are correct, this crucial next step will support studies examining antidepressant properties of cardiovascular drugs that may reverse vascular pathology and improve perfusion.
The investigators will pursue our initial goal by examining ASL predictors of nonremission to a 12-week trial of sertraline. Forty LLD subjects will complete MRI, cognitive testing, and hyperintensity assessment. ASL measured CBF will be obtained during a hypercapnia challenge and at rest with room air. This will help determine if deficits in cerebrovascular reactivity (CVR) and/or resting and on-demand CBF measures predict nonremission.
AIM: To test for differences in CVR and CBF in dorsal frontal cognitive control regions between individuals who do and do not remit to a 12-week course of sertraline (defined as MADRS ≤ 7).
Hypothesis 1: Compared with remitters, during a hypercapnia challenge nonremitters will exhibit less CVR in the dlPFC and dAC.
Hypothesis 2: Compared with remitters, while breathing room air nonremitters will exhibit lower resting CBF in the dorsal anterior cingulate (dAC) and dorsolateral prefrontal cortex (dlPFC).
Exploratory Aim: To examine the relationship between ASL measures (CVR to hypercapnia and resting CBF during normoxia) and performance in cognitive domains implicated in LLD treatment outcomes. For this Aim, we will focus on functions involving the dlPFC and dAC, specifically executive function and processing speed.
The study will enroll patients from clinical referrals and response to advertisements. In these cases, potential participants will call our study contact number. Study staff will describe the study to them, including a description of the study entry criteria. Those who continue to be interested will then be scheduled for an evaluation. After scheduling, a study physician will review their electronic medical record to assure that potential subjects meet entry criteria.
Following policies of the Vanderbilt University Health System Institutional Review Board, written informed consent will be obtained and documented by the study's Research Coordinator before any study-related procedures are performed. The study coordinator will review study procedures and the consent form with each potential participant. Each individual may take as much time as they like to decide if they do or do not wish to participate. There is no randomization. All participants receive open-label sertraline.
An initial evaluation will determine eligibility, depression severity, and evaluate medical and psychiatric history. Participants will also complete a detailed battery assessing cognitive function. During this time they will also complete the one-hour MRI session, which includes measurement of cerebral perfusion and vascular reactivity.
They will then begin the 12-week trial of open-label sertraline, allowing titration up to the maximum dose of 200mg daily. At the end of the study participants will be referred for ongoing clinical treatment.
- Conditions
- Major Depressive Disorder
- Being tested
- Sertraline
- Keywords
- Depression, Antidepressants, Elderly, Geriatrics
- 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.
SertralineDrug
Also called Zoloft
50-200mg daily
| Study group | Role | What they receive |
|---|---|---|
| Sertraline | Experimental | 50-200mg daily Receives: Drug: Sertraline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Remission of Depression
Montgomery-Asberg Depression Rating Scale (MADRS) is a measure of depression severity. This will be used to define remission as a score of 7 or less.
Measured: Week 12
Secondary outcomes (2)
Change in Clinician-rated Depression Severity
Change in depression severity will be measured by the clinician-rated Montgomery Asberg Depression Rating Scale (MADRS), range of 0-60, with higher scores indicating more severe depression
Measured: Assessed every 2 weeks from baseline to week 12, change from baseline to week 12 is reported
Change in Patient-rated Depression Severity
Change in depression severity measured by the patient-rated Quick Inventory of Depressive Symptoms, Self-Rated (QIDS-SR16). The QIDS-SR16 is a self-report measure of depression severity with a range of 0-27, with higher scores indicative of more severe depression.
Measured: Assessed every 2 weeks from baseline to week 12, change from baseline to week 12 is reported
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2013 (estimated)
- Study startJul 2013
- Primary completionJun 2016
- Study completionJun 2016
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.
- 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
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Warren Taylor, Vanderbilt University
- Investigators
- Warren D Taylor, MD, MHSc, Principal investigator, Vanderbilt University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01896934
- Sponsor's protocol ID
- 130360
- Other IDs
- R21MH099218-01A1
- Status last verified
- Jun 2017
- First submitted
- 1 Jul 2013
- Last updated
- 21 Jul 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Frontal Hypoperfusion Effects on Antidepressant Outcomes in Late-Life Depression (R21)
- ClinicalTrials.gov ID
- NCT01896934
- Acronym / sponsor ID
- 130360
- Conditions
- Major Depressive Disorder
- Keywords
- Depression, Antidepressants, Elderly, Geriatrics
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Vanderbilt UniversityUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- Jul 2013
- Primary completion
- Jun 2016 (actual)
- Study completion
- Jun 2016 (actual)
- First posted
- 11 Jul 2013 (estimated)
- Results
- Posted 21 Jul 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The long-term goal of this line of research is to determine if decreased vascular reactivity and frontal hypoperfusion is associated with poor response antidepressants. Such perfusion deficits could contribute to antidepressant nonresponse as they would hinder improvements in dorsal system metabolism seen with antidepressant treatment. The objective of the current proposal is to determine if decreased vascular reactivity and frontal hypoperfusion in depressed elders predicts and persists with antidepressant nonremission. The investigators will pursue the primary aim testing the hypothesis that decreased reactivity and hypoperfusion, specifically in the dorsolateral prefrontal cortex and dorsal anterior cingulate cortex, predict antidepressant nonremission. The investigators will enroll 40 depressed elders who will complete clinical, cognitive, and MRI assessments before and after a 12-week open-label antidepressant trial of sertraline.
Detailed description
The long-term goal of this line of research is to determine if in late-life depression (LLD), cerebrovascular dysregulation is predictive of antidepressant outcomes. The investigators hypothesize that vascular pathology resulting in reduced cerebrovascular reactivity contributes to frontocingulate hypoperfusion. Such pathology would impair neurovascular coupling and reduce the ability of the vasculature to improve frontocingulate perfusion during antidepressant treatment. Thus decreased cerebrovascular reactivity and perfusion may be a biomarker of antidepressant nonresponse. As an initial step in this research, the current study will utilize MRI arterial spin labeling (ASL) to examine if cerebrovascular reactivity deficits and resting cerebral blood flow (CBF) deficits predict antidepressant nonremission in LLD. The rationale for this proposal is that it will identify mechanisms by which vascular pathology may contribute to LLD. If the study hypotheses are correct, this crucial next step will support studies examining antidepressant properties of cardiovascular drugs that may reverse vascular pathology and improve perfusion.
The investigators will pursue our initial goal by examining ASL predictors of nonremission to a 12-week trial of sertraline. Forty LLD subjects will complete MRI, cognitive testing, and hyperintensity assessment. ASL measured CBF will be obtained during a hypercapnia challenge and at rest with room air. This will help determine if deficits in cerebrovascular reactivity (CVR) and/or resting and on-demand CBF measures predict nonremission.
AIM: To test for differences in CVR and CBF in dorsal frontal cognitive control regions between individuals who do and do not remit to a 12-week course of sertraline (defined as MADRS ≤ 7).
Hypothesis 1: Compared with remitters, during a hypercapnia challenge nonremitters will exhibit less CVR in the dlPFC and dAC.
Hypothesis 2: Compared with remitters, while breathing room air nonremitters will exhibit lower resting CBF in the dorsal anterior cingulate (dAC) and dorsolateral prefrontal cortex (dlPFC).
Exploratory Aim: To examine the relationship between ASL measures (CVR to hypercapnia and resting CBF during normoxia) and performance in cognitive domains implicated in LLD treatment outcomes. For this Aim, we will focus on functions involving the dlPFC and dAC, specifically executive function and processing speed.
The study will enroll patients from clinical referrals and response to advertisements. In these cases, potential participants will call our study contact number. Study staff will describe the study to them, including a description of the study entry criteria. Those who continue to be interested will then be scheduled for an evaluation. After scheduling, a study physician will review their electronic medical record to assure that potential subjects meet entry criteria.
Following policies of the Vanderbilt University Health System Institutional Review Board, written informed consent will be obtained and documented by the study's Research Coordinator before any study-related procedures are performed. The study coordinator will review study procedures and the consent form with each potential participant. Each individual may take as much time as they like to decide if they do or do not wish to participate. There is no randomization. All participants receive open-label sertraline.
An initial evaluation will determine eligibility, depression severity, and evaluate medical and psychiatric history. Participants will also complete a detailed battery assessing cognitive function. During this time they will also complete the one-hour MRI session, which includes measurement of cerebral perfusion and vascular reactivity.
They will then begin the 12-week trial of open-label sertraline, allowing titration up to the maximum dose of 200mg daily. At the end of the study participants will be referred for ongoing clinical treatment.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sertraline | Experimental | Drug: Sertraline50-200mg daily |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age 60 years or older.
- Current diagnosis of major depressive disorder (DSM-IV-TR), single episode, recurrent or chronic, without psychotic features, as detected by MINI and clinical exam.
- Minimum MADRS score ≥ 15.
- Mini-Mental State Exam ≥ 22.
- Ability to read and write English.
Key exclusion criteria (14 listed)
- Current or past diagnoses of other Axis I psychiatric disorders, including panic disorder and substance dependence.
- Any use of illicit substances (such as marijuana or cocaine) or abuse of prescription medications (such as benzodiazepines or opiates) within the last three months.
- Presence of acute suicidality
- Current or past psychosis
- Known primary neurological disorder, including dementia, brain tumors, epilepsy, Parkinson's disease, or demyelinating diseases
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 |
|---|---|---|
| SertralineAlso: Zoloft50-200mg daily | Drug | Sertraline |
Primary outcome
Remission of Depression
Time frame: Week 12
Montgomery-Asberg Depression Rating Scale (MADRS) is a measure of depression severity. This will be used to define remission as a score of 7 or less.
2 secondary outcomes
Change in Clinician-rated Depression Severity
Time frame: Assessed every 2 weeks from baseline to week 12, change from baseline to week 12 is reported
Change in Patient-rated Depression Severity
Time frame: Assessed every 2 weeks from baseline to week 12, change from baseline to week 12 is reported
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jul 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Warren D Taylor, MD, MHSc principal investigator
Vanderbilt University
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 in people with Major Depressive Disorder, run by Vanderbilt University 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 5 inclusion and 14 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 21 Jul 2017. 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?
Yes. Results are posted in the registry (first posted 21 Jul 2017). 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?
Remission of Depression (time frame: Week 12). 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 21 Jul 2017.