Unipolar Major DepressionPhase 4NCT02637466
Vortioxetine for MDD, Cognition, and Systemic Inflammatory Biomarkers
A Phase 4 study testing Vortioxetine in people with Unipolar Major Depression and Stage I, II or III Breast Cancer, run by University of Miami.
Trial summary
The purpose of this antidepressant study is to determine the efficacy of vortioxetine on depression and cognition in 80 women with breast cancer, and to elucidate inflammatory-mediated mechanisms by which depression and its treatment influence cancer outcome. Read more about this study
- Who is it for?
- Ages 18 to 75 years, women only
- Conditions the study is for
- Unipolar Major Depression, Stage I, II or III Breast Cancer
- What is being tested?
- Vortioxetine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Jul 2016to Jul 2019
- Phase
- Phase 4
- 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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female patients 18 to 75 years of age
- Confirmed diagnosis of Stage I, II, or III breast cancer
- Completed curative cancer treatment (surgery, chemotherapy, and/or radiotherapy) at least four weeks (≥ 4 weeks) prior to study entry no more than 5 years.
- Unipolar major depression confirmed by the mood disorder module in Structured Clinical interview for DSM-V (SCID)
- Baseline depression severity total score ≥18 by Hamilton Depression Rating Scale-21 (HDRS-21)
- Negative urine pregnancy test in women of child-bearing potential (WOCBP).
- Use of medically-established contraceptive method (e.g., contraceptive hormone therapy or intrauterine device) in women of child-bearing potential (WOCBP) or abstinence from heterosexual intercourse from the time of signing informed consent through 14 days after the last dose of study drug.
- Ability to understand and the willingness to sign a written informed consent and HIPAA document/s
Who cannot join
- 1. Other active cancers [EXCEPTION: cured skin cancer]. 2. Actively suicidal, as determined by certified mental health provider. 3. Comorbid bipolar disorder or psychosis, as diagnosed by psychiatric clinical interview conducted by a certified mental health provider.
- 4. Mini-mental state exam (MMSE) score <24 at baseline assessment 5. Current use of stimulant and/or amphetamine for cancer-related fatigue or cognitive impairment.
- 6. Use of current and effective antidepressants during study period. [NOTE: Patients who have not responded to current antidepressant may be tapered off medication prior to study entry.] 7. Uncontrolled hypothyroidism. Must be biochemically (TSH, T3, T4) and clinically euthyroid at baseline assessment.
- 8. Use of monoamine oxidase inhibitors (MAOIs) in past 14 days. 9. Concomitant use of mood stabilizer including lithium, lamictal and atypical antipsychotics 10. Failed prior therapy with vortioxetine (VTX) 11. Positive urine toxicology screen for cocaine, opiates, marijuana, amphetamines.
- 12. Comorbid alcohol and/or substance use disorder within the prior 12 months of screening, as diagnosed by psychiatric clinical interview conducted by a certified mental health provider.
About this study
Official title: A Double-blind, Placebo-controlled, Randomized Study of Vortioxetine Treatment on Major Depression, Cognition, and Systemic Inflammatory Biomarkers Associated With Depression and Cancer Progression in Women With Breast Cancer.
The purpose of this antidepressant study is to determine the efficacy of vortioxetine on depression and cognition in 80 women with breast cancer, and to elucidate inflammatory-mediated mechanisms by which depression and its treatment influence cancer outcome. Our hypothesis is that effective vortioxetine antidepressant therapy in depressed women with breast cancer will attenuate increased intermediate endpoints of inflammation that contribute to the pathogenesis of depression, cognitive impairment, and cancer progression
Read the detailed description
Major depression is an independent risk factor for incident cancer, recurrence and mortality. Women with chronic major depression exhibit a four-fold increased rate of incident breast cancer and a 39% higher mortality rate compared to non-depressed women with breast cancer. Although the precise biological mechanism linking depression with cancer progression remains unclear, elevated concentrations of systemic inflammatory biomarkers (e.g., pro-inflammatory cytokine interleukin-6 (IL-6) and associated cytokine proteins) have been independently associated with depression and cancer progression. In the context of breast cancer, secretion of tumor-derived cytokines is a known mechanism by which epithelial tumors are able to recruit immune cells (MDSCs). The presence of MDSCs at the primary tumor site favors tumor pathogenesis and correlates with more aggressive breast cancer subtypes. At the systemic level, increased levels of interleukin-6, circulating MDSCs, circulating tumor cells (CTCs) and inflammatory markers in the bloodstream of breast cancer patients are found to strongly correlate with poor prognosis.
Medical conditions such as major depression are associated with increased levels of systemic pro-inflammatory cytokines, thereby creating a host environment that promotes cancer progression. Indeed, innate immune activation and chronic inflammation have been implicated in the pathogenesis of major depression and may account for the biological mechanism linking depression and cancer progression. Several studies have shown antidepressant treatment response attenuates and normalizes pro-inflammatory cytokine plasma levels in medically-healthy patients with depression. To date, only three randomized controlled antidepressant studies have been conducted in depressed women with breast cancer. Two studies found mainserin to be effective and superior to placebo, whereas paroxetine and desipramine were comparable to placebo. Notably, several randomized controlled trials in depressed breast cancer patients found psychotherapy to be an effective depression treatment. Moreover, these studies found psychotherapy significantly lengthened survival time in depressed breast cancer patients with metastatic disease. Remarkably, no randomized controlled trials have examined the impact of antidepressant medications on cancer survival.
To date, there have been no randomized, placebo-controlled antidepressant studies in depressed women with breast cancer to investigate the impact of depression treatment on cognition and the inflammatory mediators that promote cancer progression. This study will explore the efficacy of vortioxetine on depression and cognition in women with breast cancer, and determine whether successful treatment of depression alters circulating cytokines, immune mediators, and circulating tumor cells, thus elucidating a possible mechanism to explain improved cancer outcome with effective antidepressant treatment. Given the disproportionately high rate of depression in women with breast cancer and its negative impact on cancer outcome, understanding the biological mechanism that drives this relationship is critical. This study may uncover novel immune-mediated mechanisms by which vortioxetine treatment ameliorates depression, enhances cognition, and influences cancer outcome.
Primary Objective - To assess antidepressant efficacy of vortioxetine (VTX) treatment in women with major depressive disorder (MDD) who have completed curative treatment of Stage I, II or III breast cancer.
Primary Endpoint Antidepressant efficacy will be assessed by the Hamilton Depression Rating Scale-21 (HDRS-21) total score administered at specified time points. Antidepressant response is defined as a 50% reduction in baseline HDRS-21 total score, and treatment remission is defined as an HDRS-21 total score ≤7. Antidepressants will be deemed effective if the patient's depression does not worsen. A participant's depression will be classified as "worse" if a) the participant becomes suicidal or psychotic, b) their HAM-D score increases > 18, or over a four-week period of time: c) the HAM-D score increases, and d) the CGI Improvement Rating has increased by at least one point. The definitions of antidepressant efficacy and worsening depression remain the same during Cycle 2.
- Cognitive function will be assessed by Brief Assessment of Cognition in Affective Disorders (BAC-A) test battery with measures in: (1) list learning, (2) digit sequencing task, (3) token motor task, (4) verbal fluency, (5) tower of London test, (6) symbol coding, and (7) affective processing subtest. All BAC-A measures will be administered at specified time points, and the total composite z-scores will be compared to baseline total composite z-scores.
- Being tested
- Vortioxetine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VortioxetineDrug
Also called Brilliantex
| Study group | Role | What they receive |
|---|---|---|
| Vortioxetine | Experimental | In cycle I of the study, participants will be randomized on to flexible-dose VTX (10-20 mg) versus. Vortioxetine starting dose will be 10 mg daily. Vortioxetine starting dose will be 10 mg daily with a dose escalation up to 20 mg daily at week #4. Study cycle II is an 8-week, open label treatment design for non-responders completing the Cycle I RCT. One treatment arm will continue VTX non-responders to 8 week VTX (10-20 mg/day) augmentation with cognitive behavioral therapy (10 sessions). The 2nd treatment arm will continue placebo non-responders who complete the RCT to VTX (10 to 20 mg/day). The third treatment arm will continue VTX responders/remitters who complete the RCT to open-label VTX for another 8-weeks to assess maintenance efficacy for up to 16 weeks. Receives: Drug: Vortioxetine |
| Placebo | Placebo comparator | In cycle I of the study, 80 eligible depressed women with breast cancer will be randomized into an 8-week, double-blind, placebo-controlled, flexible-dose vortioxetine (10-20 mg) treatment arm versus placebo arm.
Responders to placebo treatment will complete their study participation at the end of Cycle I, and will not proceed to Cycle II. Receives: Drug: Vortioxetine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Antidepressant efficacy
Antidepressant efficacy will be assessed by the Hamilton Depression Rating Scale-21 (HDRS-21) total score administered at specified time points. Antidepressant response is defined as a 50% reduction in baseline HDRS-21 total score, and treatment remission is defined as an HDRS-21 total score ≤7. Antidepressants will be deemed effective if the patient's depression does not worsen. A participant's depression will be classified as "worse" if a) the participant becomes suicidal or psychotic, b) their HAM-D score increases > 18, or over a four-week period of time: c) the HAM-D score increases, and d) the CGI Improvement Rating has increased by at least one point. The definitions of antidepressant efficacy and worsening depression remain the same during Cycle 2.
Measured: 4-16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Dec 2015 (estimated)
- Study startJul 2016
- Primary completionJul 2018 (estimated)
- Study completionJul 2019 (estimated)
Why it stopped: Funding not received
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Unipolar Major DepressionStudies of the same condition, open and under way.
- More trials run by University of MiamiThe 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
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Miami
- Sponsor type
- University, hospital or other
- Collaborators
- Takeda
- Responsible party
- Principal investigator, Dominique Musselman, University of Miami
- Investigators
- Dominique Musselman, M.D., MSCR, Principal investigator, University of Miami
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02637466
- Sponsor's protocol ID
- 20150753
- Status last verified
- Sep 2016
- First submitted
- 17 Dec 2015
- Last updated
- 30 Sep 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-blind, Placebo-controlled, Randomized Study of Vortioxetine Treatment on Major Depression, Cognition, and Systemic Inflammatory Biomarkers Associated With Depression and Cancer Progression in Women With Breast Cancer.
- ClinicalTrials.gov ID
- NCT02637466
- Acronym / sponsor ID
- 20150753
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Funding not received
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of MiamiUniversity, hospital or other
- Collaborators
- Takeda
- Study start
- Jul 2016
- Primary completion
- Jul 2018 (estimated)
- Study completion
- Jul 2019 (estimated)
- First posted
- 22 Dec 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.
The purpose of this antidepressant study is to determine the efficacy of vortioxetine on depression and cognition in 80 women with breast cancer, and to elucidate inflammatory-mediated mechanisms by which depression and its treatment influence cancer outcome. Our hypothesis is that effective vortioxetine antidepressant therapy in depressed women with breast cancer will attenuate increased intermediate endpoints of inflammation that contribute to the pathogenesis of depression, cognitive impairment, and cancer progression
Detailed description
Major depression is an independent risk factor for incident cancer, recurrence and mortality. Women with chronic major depression exhibit a four-fold increased rate of incident breast cancer and a 39% higher mortality rate compared to non-depressed women with breast cancer. Although the precise biological mechanism linking depression with cancer progression remains unclear, elevated concentrations of systemic inflammatory biomarkers (e.g., pro-inflammatory cytokine interleukin-6 (IL-6) and associated cytokine proteins) have been independently associated with depression and cancer progression. In the context of breast cancer, secretion of tumor-derived cytokines is a known mechanism by which epithelial tumors are able to recruit immune cells (MDSCs). The presence of MDSCs at the primary tumor site favors tumor pathogenesis and correlates with more aggressive breast cancer subtypes. At the systemic level, increased levels of interleukin-6, circulating MDSCs, circulating tumor cells (CTCs) and inflammatory markers in the bloodstream of breast cancer patients are found to strongly correlate with poor prognosis.
Medical conditions such as major depression are associated with increased levels of systemic pro-inflammatory cytokines, thereby creating a host environment that promotes cancer progression. Indeed, innate immune activation and chronic inflammation have been implicated in the pathogenesis of major depression and may account for the biological mechanism linking depression and cancer progression. Several studies have shown antidepressant treatment response attenuates and normalizes pro-inflammatory cytokine plasma levels in medically-healthy patients with depression. To date, only three randomized controlled antidepressant studies have been conducted in depressed women with breast cancer. Two studies found mainserin to be effective and superior to placebo, whereas paroxetine and desipramine were comparable to placebo. Notably, several randomized controlled trials in depressed breast cancer patients found psychotherapy to be an effective depression treatment. Moreover, these studies found psychotherapy significantly lengthened survival time in depressed breast cancer patients with metastatic disease. Remarkably, no randomized controlled trials have examined the impact of antidepressant medications on cancer survival.
To date, there have been no randomized, placebo-controlled antidepressant studies in depressed women with breast cancer to investigate the impact of depression treatment on cognition and the inflammatory mediators that promote cancer progression. This study will explore the efficacy of vortioxetine on depression and cognition in women with breast cancer, and determine whether successful treatment of depression alters circulating cytokines, immune mediators, and circulating tumor cells, thus elucidating a possible mechanism to explain improved cancer outcome with effective antidepressant treatment. Given the disproportionately high rate of depression in women with breast cancer and its negative impact on cancer outcome, understanding the biological mechanism that drives this relationship is critical. This study may uncover novel immune-mediated mechanisms by which vortioxetine treatment ameliorates depression, enhances cognition, and influences cancer outcome.
Primary Objective - To assess antidepressant efficacy of vortioxetine (VTX) treatment in women with major depressive disorder (MDD) who have completed curative treatment of Stage I, II or III breast cancer.
Primary Endpoint Antidepressant efficacy will be assessed by the Hamilton Depression Rating Scale-21 (HDRS-21) total score administered at specified time points. Antidepressant response is defined as a 50% reduction in baseline HDRS-21 total score, and treatment remission is defined as an HDRS-21 total score ≤7. Antidepressants will be deemed effective if the patient's depression does not worsen. A participant's depression will be classified as "worse" if a) the participant becomes suicidal or psychotic, b) their HAM-D score increases > 18, or over a four-week period of time: c) the HAM-D score increases, and d) the CGI Improvement Rating has increased by at least one point. The definitions of antidepressant efficacy and worsening depression remain the same during Cycle 2.
- Cognitive function will be assessed by Brief Assessment of Cognition in Affective Disorders (BAC-A) test battery with measures in: (1) list learning, (2) digit sequencing task, (3) token motor task, (4) verbal fluency, (5) tower of London test, (6) symbol coding, and (7) affective processing subtest. All BAC-A measures will be administered at specified time points, and the total composite z-scores will be compared to baseline total composite z-scores.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Vortioxetine | Experimental | Drug: VortioxetineIn cycle I of the study, participants will be randomized on to flexible-dose VTX (10-20 mg) versus. Vortioxetine starting dose will be 10 mg daily. Vortioxetine starting dose will be 10 mg daily with a dose escalation up to 20 mg daily at week #4. Study cycle II is an 8-week, open label treatment design for non-responders completing the Cycle I RCT. One treatment arm will continue VTX non-responders to 8 week VTX (10-20 mg/day) augmentation with cognitive behavioral therapy (10 sessions). The 2nd treatment arm will continue placebo non-responders who complete the RCT to VTX (10 to 20 mg/day). The third treatment arm will continue VTX responders/remitters who complete the RCT to open-label VTX for another 8-weeks to assess maintenance efficacy for up to 16 weeks. |
| Placebo | Placebo comparator | Drug: VortioxetineIn cycle I of the study, 80 eligible depressed women with breast cancer will be randomized into an 8-week, double-blind, placebo-controlled, flexible-dose vortioxetine (10-20 mg) treatment arm versus placebo arm. Responders to placebo treatment will complete their study participation at the end of Cycle I, and will not proceed to Cycle II. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Female patients 18 to 75 years of age
- Confirmed diagnosis of Stage I, II, or III breast cancer
- Completed curative cancer treatment (surgery, chemotherapy, and/or radiotherapy) at least four weeks (≥ 4 weeks) prior to study entry no more than 5 years.
- Unipolar major depression confirmed by the mood disorder module in Structured Clinical interview for DSM-V (SCID)
- Baseline depression severity total score ≥18 by Hamilton Depression Rating Scale-21 (HDRS-21)
Key exclusion criteria (5 listed)
- 1. Other active cancers [EXCEPTION: cured skin cancer]. 2. Actively suicidal, as determined by certified mental health provider. 3. Comorbid bipolar disorder or psychosis, as diagnosed by psychiatric clinical interview conducted by a certified mental health provider.
- 4. Mini-mental state exam (MMSE) score <24 at baseline assessment 5. Current use of stimulant and/or amphetamine for cancer-related fatigue or cognitive impairment.
- 6. Use of current and effective antidepressants during study period. [NOTE: Patients who have not responded to current antidepressant may be tapered off medication prior to study entry.] 7. Uncontrolled hypothyroidism. Must be biochemically (TSH, T3, T4) and clinically euthyroid at baseline assessment.
- 8. Use of monoamine oxidase inhibitors (MAOIs) in past 14 days. 9. Concomitant use of mood stabilizer including lithium, lamictal and atypical antipsychotics 10. Failed prior therapy with vortioxetine (VTX) 11. Positive urine toxicology screen for cocaine, opiates, marijuana, amphetamines.
- 12. Comorbid alcohol and/or substance use disorder within the prior 12 months of screening, as diagnosed by psychiatric clinical interview conducted by a certified mental health provider.
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: Brilliantex | Drug | Placebo, Vortioxetine |
Primary outcome
Antidepressant efficacy
Time frame: 4-16 weeks
Antidepressant efficacy will be assessed by the Hamilton Depression Rating Scale-21 (HDRS-21) total score administered at specified time points. Antidepressant response is defined as a 50% reduction in baseline HDRS-21 total score, and treatment remission is defined as an HDRS-21 total score ≤7. Antidepressants will be deemed effective if the patient's depression does not worsen. A participant's depression will be classified as "worse" if a) the participant becomes suicidal or psychotic, b) their HAM-D score increases > 18, or over a four-week period of time: c) the HAM-D score increases, and d) the CGI Improvement Rating has increased by at least one point. The definitions of antidepressant efficacy and worsening depression remain the same during Cycle 2.
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 30 Sep 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.
Dominique Musselman, M.D., MSCR principal investigator
University of Miami
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Vortioxetine in people with Unipolar Major Depression and Stage I, II or III Breast Cancer, run by University of Miami.
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 8 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: withdrawn, as of the sponsor's last update on 30 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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?
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?
Antidepressant efficacy (time frame: 4-16 weeks). 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 30 Sep 2016.