Major Depressive DisorderEarly Phase 1NCT02454426
Vortioxetine in Patients With Major Depressive Disorder and Coronary Artery Disease
A Early Phase 1 study testing Vortioxetine in people with Major Depressive Disorder and Coronary Artery Disease, run by Thomas Jefferson University at 1 site in United States.
Trial summary
This is a preliminary, open-label, clinical trial designed to assess the efficacy, safety, and tolerability of vortioxetine for the treatment of major depressive disorder in patients with coronary artery disease. In addition, the study will assess the effects of vortioxetine on heart rate variability in these patients. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Major Depressive Disorder, Coronary Artery Disease
- What is being tested?
- Vortioxetine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2016to Jun 2016
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- DSM-5 diagnosis of a major depressive disorder based on clinical evaluation by the study psychiatrist
- At least moderate severity of depression as indicated by a Montgomery-Asberg Depression Rating Scale (MADRS) score of 22 or greater
- History of coronary artery disease as defined by:
- History of coronary stenosis in one or more vessels that is greater ≥ 70% by coronary angiography or CT angiogram, OR
- History of abnormal stress test (at least medium-sized, moderate, reversible defect), OR
- History of documented myocardial infarction including ST elevation myocardial infarction or non-ST elevation myocardial infarction (with elevated troponins), OR
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- Evidence of adequate treatment of the coronary artery disease as defined by at least one of the following that was done at least six months prior to the Screening visit, AND was followed by the patient being clinically stable in the opinion of a cardiologist who has evaluated the case:
- Coronary artery bypass grafting (CABG)
- Percutaneous coronary intervention (PCI)/ stenting
- Adequate management with optimal medical treatment (such as one or more of the following medications: aspirin, beta blockers, a statin (e.g., atorvastatin), and either an ACE inhibitor or an angiotensin-receptor blocker.)
Who cannot join
- Psychiatric Exclusion Criteria:
- Patients who in the past have failed to respond to a trial of vortioxetine at the minimum recommended dose (10 mg/day) or greater taken for at least six weeks, or had unacceptable adverse effects while taking vortioxetine.
- Patients must not have failed treatment with more than one antidepressant (taken at an adequate dose and for at least six weeks) in the current episode of major depressive disorder (i.e., did not have > 50% reduction in severity of depression based on patient history)
- Patients with a current primary DSM-5 diagnosis of:
- Delirium, dementia, amnestic, or other cognitive disorder; ii) Eating Disorder (including Anorexia Nervosa or Bulimia); iii) Obsessive Compulsive Disorder; iv) Panic Disorder; v) Post-Traumatic Stress Disorder (PTSD);
- Current or past (lifetime) DSM-5 diagnosis of:
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- Bipolar I or II disorder; ii) Hypomanic episode iii) Substance-induced manic or hypomanic episode iii) Schizophrenia or other psychotic disorder
- Cardiovascular Exclusion Criteria:
- Patients who have had a myocardial infarction within 30 days of the screening visit
- Any cardiovascular condition that is unstable or decompensated
- In the opinion of the Investigators, the patient is at significant risk of cardiovascular adverse events
- Coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI)/ stenting within three months of the screening visit
- Admission to a hospital for any cardiac condition within three months of the screening visit
- Decompensated heart failure within 6 months of the screening visit
- QTc prolongation (screening ECG with QTc ≥ 450 msec for men or QTc ≥ 470 msec for women) using QTc Fridericia correction
- Second-degree (if Mobitz II) or third-degree atrioventricular block
- Heart rate on ECG of ≤ 50 bpm or ≥ 120 bpm or any heart rate that is clinically symptomatic
- Premature Ventricular Contractions (PVCs) associated with clinical symptoms and/or any complex premature ventricular contractions (ie, PVCs that are frequent [> 30/hr] or ≥ 2 beats if multifocal, or show bigeminy, trigeminy, quadrigeminy, couplets, triplets [salvos], or the R on T phenomenon)
- Atrial fibrillation or flutter
- Supine (after patient has been supine for 5 minutes) systolic BP > 160 mm Hg or < 90 mm Hg or diastolic BP > 100 mm Hg or any systolic or diastolic BP that is symptomatic or clinically significant based on the opinion of the Principal Investigator
- Patients who are receiving warfarin
Trial locations and contacts
1 site in 1 country.
United States1 site
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
About this study
Official title: An 8-week, Open-Label Clinical Trial of the Efficacy and Safety of Vortioxetine in Patients With Major Depressive Disorder and Coronary Artery Disease
This is a preliminary, open-label, clinical trial designed to assess the efficacy, safety, and tolerability of vortioxetine for the treatment of major depressive disorder in patients with coronary artery disease. In addition, the study will assess the effects of vortioxetine on heart rate variability in these patients.
Read the detailed description
Comorbid Major Depressive Disorder (MDD) and Coronary Artery Disease (CAD) are common:
Major depressive disorder is a highly prevalent disorder that is serious, and in some cases life-threatening, condition. The 12-month prevalence of major depressive disorder in the United States is 6.6% (Kessler et al., 2003). Coronary artery disease (CAD) is also a large and growing problem in the United States. According to the 2014 American Heart Association (AHA) report on heart disease and stroke statistics, an estimated 15.4 million Americans ≥20 years of age have coronary artery disease. The total prevalence of coronary artery disease in this population is estimated to be 6.4%, with a prevalence of 7.9% in men and 5.1% in women. By the year 2030, the prevalence of coronary artery disease is projected to increase approximately 18% from 2013 estimates (Go et al., 2014). Thus, patients with major depressive disorder and comorbid CAD represent a large population of patients.
Depression in patients with CAD is clinically important:
Depression frequently accompanies coronary artery disease and has been linked more somatic symptoms, hospitalizations, increased financial burden, and poorer quality of life, as well as being a predictor of worse outcomes of cardiac disease. Reduction of cardiac risk factors is less likely to be successful in depressed patients. Depression may also interfere with medication adherence, as depressed patients are three times as likely to be noncompliant with their medication regimens. In addition, depression is associated with decreased rates of participation in cardiac rehabilitation, higher healthcare utilization and costs, and greatly reduced quality of life (Lichtman et al., 2009). Due to these effects of depression on coronary artery disease, there is increasing recognition that depression should be formally considered a risk factor for adverse medical outcomes in patients with acute coronary syndrome (Lichtman et al., 2014).
Thus, there is a great, unmet clinical need to treat patients with major depressive disorder and coronary artery disease.
In addition to the older tricyclic antidepressants, the newer serotonin-norepinephrine reuptake inhibitors are also associated with cardiovascular risks like hypertension, orthostatic hypotension, and perhaps QTc prolongation (Mago et al., 2014). Vortioxetine is a newly approved antidepressant thought to work by combining modulation of 5-HT receptor subtypes and inhibition of the serotonin transporter (Citrome, 2014). Early data suggests that this multimodal mechanism of action results in increased brain levels of serotonin, dopamine, and noradrenaline in the prefrontal cortex (Pehrson et al., 2013). Clinical trials of vortioxetine for major depressive disorder have not shown any cardiovascular adverse effects (Mago et al., 2014).
Heart Rate Variability (HRV) Heart Rate Variability is a measure is based on the changes in the interval between consecutive heart beats and between consecutive instantaneous heart rates. It has become the conventionally accepted term to describe variations of both instantaneous heart rate and RR intervals. Long term reduced heart rate variability can lead to immune dysfunction and inflammation, cardiovascular disease and mortality (Newhouse, 2014). Several studies in depressive patients have shown reduced heart rate variability that suggests an increased sympathetic activity and/or reduced vagal activity (Carney et al., 2009). Thus, treating depression effectively may reduce heart rate variability, which is a surrogate marker for better cardiovascular outcomes.
The proposed study has been planned as a pilot, open-label study of the use, for the first time, of vortioxetine in patients with documented coronary disease. Therefore, the sample size is not based on a formal sample size calculation but on feasibility of a small study that, if positive, can lead to a future larger, adequately powered study. A sample size of 25 patients is appropriate for the present purpose. The results of this proposed study would inform sample size calculation for a future, larger study.
- Conditions
- Major Depressive Disorder, Coronary Artery Disease
- Being tested
- Vortioxetine
- Keywords
- Depression, Heart disease
- Medical subject headings
- Depressive Disorder, Major, Coronary Artery Disease, Depression, Heart Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VortioxetineDrug
Also called Brintellix
open label treatment
| Study group | Role | What they receive |
|---|---|---|
| Open-Label Treatment | Experimental | Patients will be initiated on vortioxetine 5 mg/day for 4 days, then increased to 10 mg/day. After the week 2 visit, patients will then be increased to 20 mg/day for the remainder of the study Receives: Drug: Vortioxetine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Severity of depressive episodes measured using the Montgomery-Asberg Depression Rating Scale (MADRS)
Measured: Baseline-Week 10
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 May 2015 (estimated)
- Study startApr 2016
- Primary completionJun 2016
- Study completionJun 2016
Why it stopped: PI left institution
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.
- More trials run by Thomas Jefferson UniversityThe 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Thomas Jefferson University
- Sponsor type
- University, hospital or other
- Collaborators
- Takeda
- Responsible party
- Sponsor
- Investigators
- Rajnish Mago, MD, Principal investigator, Thomas Jefferson University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02454426
- Sponsor's protocol ID
- TakedaHRV
- Status last verified
- Aug 2016
- First submitted
- 21 May 2015
- Last updated
- 25 Aug 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An 8-week, Open-Label Clinical Trial of the Efficacy and Safety of Vortioxetine in Patients With Major Depressive Disorder and Coronary Artery Disease
- ClinicalTrials.gov ID
- NCT02454426
- Acronym / sponsor ID
- TakedaHRV
- Conditions
- Major Depressive Disorder, Coronary Artery Disease
- Keywords
- Depression, Heart disease
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: PI left institution
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Thomas Jefferson UniversityUniversity, hospital or other
- Collaborators
- Takeda
- Study start
- Apr 2016
- Primary completion
- Jun 2016 (actual)
- Study completion
- Jun 2016 (actual)
- First posted
- 27 May 2015 (estimated)
- 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 is a preliminary, open-label, clinical trial designed to assess the efficacy, safety, and tolerability of vortioxetine for the treatment of major depressive disorder in patients with coronary artery disease. In addition, the study will assess the effects of vortioxetine on heart rate variability in these patients.
Detailed description
Comorbid Major Depressive Disorder (MDD) and Coronary Artery Disease (CAD) are common:
Major depressive disorder is a highly prevalent disorder that is serious, and in some cases life-threatening, condition. The 12-month prevalence of major depressive disorder in the United States is 6.6% (Kessler et al., 2003). Coronary artery disease (CAD) is also a large and growing problem in the United States. According to the 2014 American Heart Association (AHA) report on heart disease and stroke statistics, an estimated 15.4 million Americans ≥20 years of age have coronary artery disease. The total prevalence of coronary artery disease in this population is estimated to be 6.4%, with a prevalence of 7.9% in men and 5.1% in women. By the year 2030, the prevalence of coronary artery disease is projected to increase approximately 18% from 2013 estimates (Go et al., 2014). Thus, patients with major depressive disorder and comorbid CAD represent a large population of patients.
Depression in patients with CAD is clinically important:
Depression frequently accompanies coronary artery disease and has been linked more somatic symptoms, hospitalizations, increased financial burden, and poorer quality of life, as well as being a predictor of worse outcomes of cardiac disease. Reduction of cardiac risk factors is less likely to be successful in depressed patients. Depression may also interfere with medication adherence, as depressed patients are three times as likely to be noncompliant with their medication regimens. In addition, depression is associated with decreased rates of participation in cardiac rehabilitation, higher healthcare utilization and costs, and greatly reduced quality of life (Lichtman et al., 2009). Due to these effects of depression on coronary artery disease, there is increasing recognition that depression should be formally considered a risk factor for adverse medical outcomes in patients with acute coronary syndrome (Lichtman et al., 2014).
Thus, there is a great, unmet clinical need to treat patients with major depressive disorder and coronary artery disease.
In addition to the older tricyclic antidepressants, the newer serotonin-norepinephrine reuptake inhibitors are also associated with cardiovascular risks like hypertension, orthostatic hypotension, and perhaps QTc prolongation (Mago et al., 2014). Vortioxetine is a newly approved antidepressant thought to work by combining modulation of 5-HT receptor subtypes and inhibition of the serotonin transporter (Citrome, 2014). Early data suggests that this multimodal mechanism of action results in increased brain levels of serotonin, dopamine, and noradrenaline in the prefrontal cortex (Pehrson et al., 2013). Clinical trials of vortioxetine for major depressive disorder have not shown any cardiovascular adverse effects (Mago et al., 2014).
Heart Rate Variability (HRV) Heart Rate Variability is a measure is based on the changes in the interval between consecutive heart beats and between consecutive instantaneous heart rates. It has become the conventionally accepted term to describe variations of both instantaneous heart rate and RR intervals. Long term reduced heart rate variability can lead to immune dysfunction and inflammation, cardiovascular disease and mortality (Newhouse, 2014). Several studies in depressive patients have shown reduced heart rate variability that suggests an increased sympathetic activity and/or reduced vagal activity (Carney et al., 2009). Thus, treating depression effectively may reduce heart rate variability, which is a surrogate marker for better cardiovascular outcomes.
The proposed study has been planned as a pilot, open-label study of the use, for the first time, of vortioxetine in patients with documented coronary disease. Therefore, the sample size is not based on a formal sample size calculation but on feasibility of a small study that, if positive, can lead to a future larger, adequately powered study. A sample size of 25 patients is appropriate for the present purpose. The results of this proposed study would inform sample size calculation for a future, larger study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Open-Label Treatment | Experimental | Drug: VortioxetinePatients will be initiated on vortioxetine 5 mg/day for 4 days, then increased to 10 mg/day. After the week 2 visit, patients will then be increased to 20 mg/day for the remainder of the study |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- DSM-5 diagnosis of a major depressive disorder based on clinical evaluation by the study psychiatrist
- At least moderate severity of depression as indicated by a Montgomery-Asberg Depression Rating Scale (MADRS) score of 22 or greater
- History of coronary artery disease as defined by:
- Evidence of adequate treatment of the coronary artery disease as defined by at least one of the following that was done at least six months prior to the Screening visit, AND was followed by the patient being clinically stable in the opinion of a cardiologist who has evaluated the case:
Key exclusion criteria (21 listed)
- Patients who in the past have failed to respond to a trial of vortioxetine at the minimum recommended dose (10 mg/day) or greater taken for at least six weeks, or had unacceptable adverse effects while taking vortioxetine.
- Patients must not have failed treatment with more than one antidepressant (taken at an adequate dose and for at least six weeks) in the current episode of major depressive disorder (i.e., did not have > 50% reduction in severity of depression based on patient history)
- Patients with a current primary DSM-5 diagnosis of:
- Current or past (lifetime) DSM-5 diagnosis of:
- Patients who have had a myocardial infarction within 30 days of the screening visit
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 |
|---|---|---|
| VortioxetineAlso: Brintellixopen label treatment | Drug | Open-Label Treatment |
Primary outcome
Severity of depressive episodes measured using the Montgomery-Asberg Depression Rating Scale (MADRS)
Time frame: Baseline-Week 10
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Aug 2016.
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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.
Rajnish Mago, MD principal investigator
Thomas Jefferson University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Vortioxetine in people with Major Depressive Disorder and Coronary Artery Disease, run by Thomas Jefferson 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 10 inclusion and 21 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: withdrawn, as of the sponsor's last update on 25 Aug 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Severity of depressive episodes measured using the Montgomery-Asberg Depression Rating Scale (MADRS) (time frame: Baseline-Week 10). 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 25 Aug 2016.