DepressionPhase 4NCT01794455
Effects of Cerebral Hypoperfusion and Its Reversal on Late-Life Depression
A Phase 4 study testing Sertraline and Candesartan in people with Depression and Hypertension, run by Vanderbilt University at 1 site in United States.
Trial summary
This pilot proposal will test the hypothesis that altered cerebral vessel reactivity and cerebral hypoperfusion (decreased blood flow to the brain) is a core mechanism underlying the relationship between vascular disease and depression in older adults. Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Depression, Hypertension
- What is being tested?
- Sertraline and Candesartan
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- May 2013to Mar 2015
- 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
- Diagnosis of Major Depressive Disorder, single or recurrent episode, without psychotic features by Diagnostic and Statistical Manual IV Text Revision (DSMIV-TR) criteria
- Presence of hypertension (defined as systolic > 140 or diastolic > 90 or currently receiving antihypertensive therapy)
- Minimum depression severity of ≥ 15 on the Montgomery-Asberg Depression Rating Scale (MADRS)
- Cognitively intact or with mild cognitive deficits, with a minimum score ≥ 23 on the Montreal Cognitive Assessment (MoCA).
Who cannot join
- Other psychiatric Axis I disorders
- Acute suicidality
- Electroconvulsive therapy in the last 6 months
- Primary neurological disorder, including dementia and stroke
- Significant cardiovascular disease, specifically diagnosis of congestive heart failure, known bilateral renal artery stenosis, symptomatic hypotension, or critical aortic or mitral stenosis
- Myocardial infarction or open-heart surgery in last 6 weeks
Show all 14Show fewer
- Serum creatinine ≥ 265 micromol /L
- Serum potassium ≥ 5.5 mmol/L
- MRI contraindications
- Known allergy to sertraline or candesartan specifically or known allergy to other SSRIs or ARBs.
- History of prolonged (> 3 weeks) or self-described severe discontinuation syndrome in the past after stopping an antidepressant.
- Current use of an angiotensin receptor blocker
- Current or planned psychotherapy
- 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 acute respiratory disease, chronic angina, or other unstable cardiac conditions.
Trial locations and contacts
1 site in 1 country.
United States1 site
Vanderbilt Psychiatric Hospital
Nashville, Tennessee, 37212
About this study
This pilot proposal will test the hypothesis that altered cerebral vessel reactivity and cerebral hypoperfusion (decreased blood flow to the brain) is a core mechanism underlying the relationship between vascular disease and depression in older adults. The long-term objective of this line of research is to: A) determine the relationship between vascular reactivity, cerebral hypoperfusion and the persistence of late-life depression and B) determine if improving cerebral perfusion with angiotensin receptor blockers (ARBs) improves depression outcomes.
Read the detailed description
This study will examine how magnetic resonance imaging (MRI) measures of cerebral perfusion relate to antidepressant response. There are two phases to the study. In the first phase, we will examine how cerebral perfusion is related to response to sertraline, a commonly used antidepressant. In the second phase, we will examine individuals who do not respond to sertraline or other selective serotonin reuptake inhibitors (SSRI). We will examine if candesartan, an ARB, improves depression and if it does so by improving cerebral perfusion.
After providing informed consent, participants will undergo medical and psychiatric screening. Participants determined to be eligible at the screen will proceed to a baseline evaluation, which will include brief cognitive neuropsychological testing and MRI. Participants will then begin open-label sertraline for eight weeks (baseline to week 8). Dosing will begin at 50mg daily and, based on response and tolerability, can increase up to the FDA approved maximum dose of 200mg daily.
After the eight weeks, participants will be re-evaluated and complete another MRI. Those who respond to sertraline and experience remission of their depression will end their study participation. Those who do not experience remission will continue to the phase 2 open-label candesartan arm.
The candesartan arm will last for 12 weeks (week 8 to week 20). Dosing will begin at 4mg daily and can increase to a maximum dose of 32mg, based on tolerability and response. Participants will be monitored closely, and other antihypertensive medications adjusted to avoid low blood pressure. At the end of the 12-week trial, participants will again complete MRI and neuropsychological testing. Their study participation will then end.
- Conditions
- Depression, Hypertension
- Being tested
- Sertraline, Candesartan
- Keywords
- Depression, Depressive Disorder, Geriatrics, Hypertension
- Medical subject headings
- Depression, Hypertension, Depressive Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SertralineDrug
Also called Zoloft
50mg - 200mg daily
CandesartanDrug
Also called Atacand
4mg - 32mg daily
| Study group | Role | What they receive |
|---|---|---|
| Phase 1: Sertraline | Experimental | Eight-week trial of sertraline mono therapy, dosing ranging from 50mg- 200mg daily. Receives: Drug: Sertraline |
| Phase 2: Candesartan | Experimental | For subjects who do not remit to sertraline, they will receive candesartan for 12 weeks, with doses ranging from 4mg - 32mg daily. Receives: Drug: Candesartan |
What is being measured
The primary outcome is the main question the study is designed to answer.
MRI Arterial Spin Labeling
MRI arterial spin labeling is a noninvasive approach to measuring cerebral blood flow. This relates to the Phase 1 sertraline arm.
Measured: Change in perfusion from baseline to week 8
Montgomery Asberg Depression Rating Scale (MADRS)
MADRS is a measure of depression severity. This outcome applies to the sertraline Phase 1 arm.
Measured: Week 8
Secondary outcomes (4)
Quick Inventory of Depressive Symptoms, Self-Rated (QIDS-SR16)
Self-report measure of depression severity. This applies to the sertraline Phase 1 arm.
Measured: Week 8
Quick Inventory of Depressive Symptoms, Self-Rated (QIDS-SR16)
Self-report measure of depression severity (range 0 - 27, higher scores indicate more severe depressive symptoms). This applies to the candesartan Phase 2 arm.
Measured: Week 20
Montgomery-Asberg Depression Rating Scale
MADRS is a measure of depression severity (range 0 - 60, higher scores indicate more severe depressive symptoms). This outcome applies to the candesartan Phase 2 arm.
Measured: Week 20
MRI Arterial Spin Labeling
MRI arterial spin labeling is a noninvasive approach to measuring cerebral blood flow. This relates to the Phase 2 candesartan arm.
Measured: Change from week 8 to week 20
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Feb 2013 (estimated)
- Study startMay 2013
- Primary completionMar 2015
- Study completionMar 2015
Why it stopped: Enrollment difficulties
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 DepressionStudies 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University
- Sponsor type
- University, hospital or other
- 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
- NCT01794455
- Sponsor's protocol ID
- VR5642
- Status last verified
- Aug 2016
- First submitted
- 12 Feb 2013
- Last updated
- 20 Oct 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Cerebral Hypoperfusion and Its Reversal on Late-Life Depression
- ClinicalTrials.gov ID
- NCT01794455
- Acronym / sponsor ID
- VR5642
- Conditions
- Depression, Hypertension
- Keywords
- Depression, Depressive Disorder, Geriatrics, Hypertension
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Enrollment difficulties
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Vanderbilt UniversityUniversity, hospital or other
- Study start
- May 2013
- Primary completion
- Mar 2015 (actual)
- Study completion
- Mar 2015 (actual)
- First posted
- 18 Feb 2013 (estimated)
- Results
- Posted 20 Oct 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This pilot proposal will test the hypothesis that altered cerebral vessel reactivity and cerebral hypoperfusion (decreased blood flow to the brain) is a core mechanism underlying the relationship between vascular disease and depression in older adults. The long-term objective of this line of research is to: A) determine the relationship between vascular reactivity, cerebral hypoperfusion and the persistence of late-life depression and B) determine if improving cerebral perfusion with angiotensin receptor blockers (ARBs) improves depression outcomes.
Detailed description
This study will examine how magnetic resonance imaging (MRI) measures of cerebral perfusion relate to antidepressant response. There are two phases to the study. In the first phase, we will examine how cerebral perfusion is related to response to sertraline, a commonly used antidepressant. In the second phase, we will examine individuals who do not respond to sertraline or other selective serotonin reuptake inhibitors (SSRI). We will examine if candesartan, an ARB, improves depression and if it does so by improving cerebral perfusion.
After providing informed consent, participants will undergo medical and psychiatric screening. Participants determined to be eligible at the screen will proceed to a baseline evaluation, which will include brief cognitive neuropsychological testing and MRI. Participants will then begin open-label sertraline for eight weeks (baseline to week 8). Dosing will begin at 50mg daily and, based on response and tolerability, can increase up to the FDA approved maximum dose of 200mg daily.
After the eight weeks, participants will be re-evaluated and complete another MRI. Those who respond to sertraline and experience remission of their depression will end their study participation. Those who do not experience remission will continue to the phase 2 open-label candesartan arm.
The candesartan arm will last for 12 weeks (week 8 to week 20). Dosing will begin at 4mg daily and can increase to a maximum dose of 32mg, based on tolerability and response. Participants will be monitored closely, and other antihypertensive medications adjusted to avoid low blood pressure. At the end of the 12-week trial, participants will again complete MRI and neuropsychological testing. Their study participation will then end.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Phase 1: Sertraline | Experimental | Drug: SertralineEight-week trial of sertraline mono therapy, dosing ranging from 50mg- 200mg daily. |
| Phase 2: Candesartan | Experimental | Drug: CandesartanFor subjects who do not remit to sertraline, they will receive candesartan for 12 weeks, with doses ranging from 4mg - 32mg 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
- Diagnosis of Major Depressive Disorder, single or recurrent episode, without psychotic features by Diagnostic and Statistical Manual IV Text Revision (DSMIV-TR) criteria
- Presence of hypertension (defined as systolic > 140 or diastolic > 90 or currently receiving antihypertensive therapy)
- Minimum depression severity of ≥ 15 on the Montgomery-Asberg Depression Rating Scale (MADRS)
- Cognitively intact or with mild cognitive deficits, with a minimum score ≥ 23 on the Montreal Cognitive Assessment (MoCA).
Key exclusion criteria (14 listed)
- Other psychiatric Axis I disorders
- Acute suicidality
- Electroconvulsive therapy in the last 6 months
- Primary neurological disorder, including dementia and stroke
- Significant cardiovascular disease, specifically diagnosis of congestive heart failure, known bilateral renal artery stenosis, symptomatic hypotension, or critical aortic or mitral stenosis
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: Zoloft50mg - 200mg daily | Drug | Phase 1: Sertraline |
| CandesartanAlso: Atacand4mg - 32mg daily | Drug | Phase 2: Candesartan |
Primary outcome
MRI Arterial Spin Labeling
Time frame: Change in perfusion from baseline to week 8
MRI arterial spin labeling is a noninvasive approach to measuring cerebral blood flow. This relates to the Phase 1 sertraline arm.
Montgomery Asberg Depression Rating Scale (MADRS)
Time frame: Week 8
MADRS is a measure of depression severity. This outcome applies to the sertraline Phase 1 arm.
4 secondary outcomes
Quick Inventory of Depressive Symptoms, Self-Rated (QIDS-SR16)
Time frame: Week 8
Quick Inventory of Depressive Symptoms, Self-Rated (QIDS-SR16)
Time frame: Week 20
Montgomery-Asberg Depression Rating Scale
Time frame: Week 20
MRI Arterial Spin Labeling
Time frame: Change from week 8 to week 20
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Oct 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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.
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 and Candesartan in people with Depression and Hypertension, 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: stopped early, as of the sponsor's last update on 20 Oct 2016. 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 20 Oct 2016). 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?
MRI Arterial Spin Labeling (time frame: Change in perfusion from baseline to week 8). 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?
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 20 Oct 2016.