TBIPhase 3NCT02845349
Vortioxetine for the Treatment of Major Depression and Co-morbidities After Traumatic Brain Injury (TBI)
A Phase 3 study testing Vortioxetine in people with TBI and Major Depression, run by Johns Hopkins University.
Trial summary
Traumatic brain injury (TBI) is a major public health problem with an annual incidence of about 1.7 million per year. TBI is associated with various long-term morbidities. Among them, psychiatric disturbances are the major cause of chronic disability and poor quality of life. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- TBI, Major Depression
- 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
- Oct 2016to Oct 2018
- Phase
- Phase 3
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults aged 18 and over
- Meet Department of Defense Criteria for TBI
- Meet DSM 5 criteria for major depression
- Score greater than 16 on the HAM D17
- Currently not on any psychotropics for treatment of depression
Who cannot join
- Subjects who are medically or psychiatrically unstable
- Pregnant women
- History of active substance abuse x 1 month
- Other neurological problems, or a diagnosis of schizophrenia, dementia, or bipolar disorder
- Prior treatment with vortioxetine
About this study
Official title: Vortioxetine for the Treatment of Major Depression and Neuropsychiatric Co-morbidities After Traumatic Brain Injury (TBI)
Traumatic brain injury (TBI) is a major public health problem with an annual incidence of about 1.7 million per year. TBI is associated with various long-term morbidities. Among them, psychiatric disturbances are the major cause of chronic disability and poor quality of life. Major depression is the common psychiatric sequela post TBI with rates ranging from 13% at 1 year to 60% at 8 years after TBI. Major depression after TBI (henceforth referred to as TBI depression) is often associated with comorbid neuropsychiatric symptoms (NPS) such as anxiety, aggression, substance abuse and cognitive deficits that often makes treatment difficult. Despite increased rates of depression, there is no Food and Drug Administration (FDA) approved drug/s for its treatment.
The investigators propose to address these limitations by use of a novel serotonergic agent, vortioxetine, which has a multimodal mechanism of action through serotonin transporter (SERT) inhibition, 5-hydroxytryptamine (5-HT)3, 7, and 1D receptor antagonism, 1B receptor partial agonism, and 1A receptor agonism.
Read more
Overarching Goal: The overarching goal of the proposed pilot study is to determine the effectiveness and safety of vortioxetine for the treatment of post-TBI depression and co-morbid NPS.
Study Design: The study design will include a DBPCT of 30 TBI patients of all severities who meet the DSM 5 criteria for major depression. A total of 150 will be consented to allow for screen failures. Written informed consent will be obtained from these patients. Subjects will be followed for a total of 12 weeks. Subjects will be randomized to either the vortioxetine arm (N=15) or placebo arm (N=15). The treatment group will receive vortioxetine 10mg per day, which will be increased to 20 mg or decreased to 5 mg, if deemed clinically necessary, at week 4 or 8. Subjects will have a total of 4-5 visits: Baseline evaluation (1 or 2 visits) and follow-up visits at weeks 4, 8 and 12. Well-validated psychiatric instruments will be used to compare the effectiveness of vortioxetine versus placebo treatment at week 12 compared to baseline Relevance: This study has the potential to provide strong preliminary evidence for the use of vortioxetine as a safe and novel agent for treatment of TBI depression and its psychiatric co-morbidities. If found to be effective, results from this study can be used to design larger studies and also determine brain changes associated with its use via neuroimaging.
Read the detailed description
In this study the investigators propose to recruit 30 outpatients with TBI of varying degrees of severity who also meet DSM 5 criteria for major depression. The investigators will screen as many potential subjects as possible to get a total of 30 participants who meet the study criteria and complete the study ( Total 30 study completers). Written informed consent will be obtained from all participants prior to collection of any data. Participants will be evaluated using well validated psychiatric instruments Participants will be recruited from several sources: (1) Brain Injury Clinic at Johns Hopkins Bayview Medical Center; (2) referral from other Hopkins outpatient clinics; (3) Brain injury support groups organized by the Brain Injury Association of Maryland, and (4) Advertisements placed in local newspapers and (5) Trial Facts - an online recruiting source. The study sites will be at the Geriatric \& Neuropsychiatry clinics at Johns Hopkins Bayview Medical Center.
Overarching Goal: The overarching goal of the proposed pilot study is to determine the effectiveness and safety of vortioxetine for the treatment of post-TBI depression and co-morbid neuropsychiatric symptoms (NPS).
Study Design: The study design will include a Double Blinded Placebo Controlled Trial (DBPCT) of 30 TBI patients of all severities who meet the DSM 5 criteria for major depression. A total of 150 will be consented to allow for screen failures. Written informed consent will be obtained from these patients. Subjects will be followed for a total of 12 weeks. Subjects will be randomized to either the vortioxetine arm (N=15) or placebo arm (N=15). The treatment group will receive vortioxetine 10mg per day, which will be increased to 20 mg or decreased to 5 mg, if deemed clinically necessary, at week 4 or 8. Subjects will have a total of 4-5 visits: Baseline evaluation (1 or 2 visits) and follow-up visits at weeks 4, 8 and 12.
Well-validated psychiatric instruments will be used to compare the effectiveness of vortioxetine versus placebo treatment at week 12 compared to baseline for the treatment of major depression and its neuropsychiatric co-morbidities.
Relevance: This study has the potential to provide strong preliminary evidence for the use of vortioxetine as a safe and novel agent for treatment of TBI depression and its psychiatric co-morbidities. If found to be effective, results from this study can be used to design larger studies and also determine brain changes associated with its use via neuroimaging. Depression is common in other neurological disorders such as stroke, multiple sclerosis, Parkinson's disease, and dementia syndromes. Results from this study can shed light in the management of depression in other neurological disorders.
- Conditions
- TBI, Major Depression
- Being tested
- Vortioxetine, Placebo
- 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.
VortioxetineDrug
Also called Trintellix
The study drug, vortioxetine received approval from the U.S. Food and Drug Administration (FDA) to treat adults with major depressive disorder. This study is being done to determine its effectiveness in a specialized population, i.e. those who have developed major depression after a traumatic brain injury. As patients who have sustained a TBI are medically fragile and sensitive to side-effects of medications, it is important to test the effectiveness and safety of vortioxetine in this population.
PlaceboDrug
Also called Sugar pill
A placebo comparator will be used in one subset of patients.
| Study group | Role | What they receive |
|---|---|---|
| Drug-Vortioxetine | Experimental | The treatment group will receive vortioxetine 10 mg per day, which will be increased to 20 mg or decreased to 5 mg, if deemed clinically necessary, at week 4 or 8. Receives: Drug: Vortioxetine |
| Placebo | Placebo comparator | Matching placebo will be used. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Reduction of depressive symptoms at 12 weeks as assessed by the Hamilton Depression Scale 17 items (HAMD-17)
Measured: at 12 weeks
Reduction of depressive symptoms at 12 weeks as assessed by the Clinical Global Impression Improvement (CGI-I) scale
Measured: at 12 weeks
Secondary outcomes (3)
Comparison of rates and severity of side-effects and adverse effects in subjects in the treatment arm versus placebo at week 1-12
Measured: Up to 12 weeks
Change from baseline at week 12 on the Columbia-Suicide Severity Rating Scale (C-SSRS)
Measured: baseline and at 12 weeks
Change from baseline at week 12 on the Arizona Sexual Experience (ASEX) scale
Measured: baseline and at 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2016 (estimated)
- Study startOct 2016
- Primary completionOct 2018 (estimated)
- Study completionOct 2018 (estimated)
Why it stopped: Funding withdrawn.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for TBIStudies of the same condition, open and under way.
- More trials run by Johns Hopkins 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
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Collaborators
- Takeda
- Responsible party
- Sponsor
- Investigators
- Vani Rao, MD, Principal investigator, Johns University and School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02845349
- Sponsor's protocol ID
- IRB00105196
- Status last verified
- Sep 2016
- First submitted
- 18 Jul 2016
- Last updated
- 2 Sep 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No: Prior to the initiation of the study, a method will be developed for data collection. Each participant will have a study folder with a unique identifying number to contain the results of study tests and evaluations. Another folder will also be kept that will hold all consent forms and identifying demographic information. The folders will be reviewed monthly for inconsistencies. The data will be entered into a database maintained in the Neuropsychiatry Division of Johns Hopkins Bayview Medical Center, which is password protected and only the PI and her Research team will have access to the study folders and database. The data monitoring committee will include Dr. Rao (PI), and members of the Data \& Safety monitoring board: Drs. Christopher Marano, Paul Rosenberg and Jin Joo. All members of the Diagnostic and Statistical Manual of Mental Disorders (DSM) board are psychiatrists and faculty Johns Hopkins University. The 3 DSM members are not connected with the study.
Study at a glance
From the registry record, last updated by the sponsor on 2 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Vortioxetine for the Treatment of Major Depression and Neuropsychiatric Co-morbidities After Traumatic Brain Injury (TBI)
- ClinicalTrials.gov ID
- NCT02845349
- Acronym / sponsor ID
- IRB00105196
- Conditions
- TBI, Major Depression
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Funding withdrawn.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Collaborators
- Takeda
- Study start
- Oct 2016
- Primary completion
- Oct 2018 (estimated)
- Study completion
- Oct 2018 (estimated)
- First posted
- 27 Jul 2016 (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.
Traumatic brain injury (TBI) is a major public health problem with an annual incidence of about 1.7 million per year. TBI is associated with various long-term morbidities. Among them, psychiatric disturbances are the major cause of chronic disability and poor quality of life. Major depression is the common psychiatric sequela post TBI with rates ranging from 13% at 1 year to 60% at 8 years after TBI. Major depression after TBI (henceforth referred to as TBI depression) is often associated with comorbid neuropsychiatric symptoms (NPS) such as anxiety, aggression, substance abuse and cognitive deficits that often makes treatment difficult. Despite increased rates of depression, there is no Food and Drug Administration (FDA) approved drug/s for its treatment.
The investigators propose to address these limitations by use of a novel serotonergic agent, vortioxetine, which has a multimodal mechanism of action through serotonin transporter (SERT) inhibition, 5-hydroxytryptamine (5-HT)3, 7, and 1D receptor antagonism, 1B receptor partial agonism, and 1A receptor agonism.
Overarching Goal: The overarching goal of the proposed pilot study is to determine the effectiveness and safety of vortioxetine for the treatment of post-TBI depression and co-morbid NPS.
Study Design: The study design will include a DBPCT of 30 TBI patients of all severities who meet the DSM 5 criteria for major depression. A total of 150 will be consented to allow for screen failures. Written informed consent will be obtained from these patients. Subjects will be followed for a total of 12 weeks. Subjects will be randomized to either the vortioxetine arm (N=15) or placebo arm (N=15). The treatment group will receive vortioxetine 10mg per day, which will be increased to 20 mg or decreased to 5 mg, if deemed clinically necessary, at week 4 or 8. Subjects will have a total of 4-5 visits: Baseline evaluation (1 or 2 visits) and follow-up visits at weeks 4, 8 and 12. Well-validated psychiatric instruments will be used to compare the effectiveness of vortioxetine versus placebo treatment at week 12 compared to baseline Relevance: This study has the potential to provide strong preliminary evidence for the use of vortioxetine as a safe and novel agent for treatment of TBI depression and its psychiatric co-morbidities. If found to be effective, results from this study can be used to design larger studies and also determine brain changes associated with its use via neuroimaging.
Detailed description
In this study the investigators propose to recruit 30 outpatients with TBI of varying degrees of severity who also meet DSM 5 criteria for major depression. The investigators will screen as many potential subjects as possible to get a total of 30 participants who meet the study criteria and complete the study ( Total 30 study completers). Written informed consent will be obtained from all participants prior to collection of any data. Participants will be evaluated using well validated psychiatric instruments Participants will be recruited from several sources: (1) Brain Injury Clinic at Johns Hopkins Bayview Medical Center; (2) referral from other Hopkins outpatient clinics; (3) Brain injury support groups organized by the Brain Injury Association of Maryland, and (4) Advertisements placed in local newspapers and (5) Trial Facts - an online recruiting source. The study sites will be at the Geriatric \& Neuropsychiatry clinics at Johns Hopkins Bayview Medical Center.
Overarching Goal: The overarching goal of the proposed pilot study is to determine the effectiveness and safety of vortioxetine for the treatment of post-TBI depression and co-morbid neuropsychiatric symptoms (NPS).
Study Design: The study design will include a Double Blinded Placebo Controlled Trial (DBPCT) of 30 TBI patients of all severities who meet the DSM 5 criteria for major depression. A total of 150 will be consented to allow for screen failures. Written informed consent will be obtained from these patients. Subjects will be followed for a total of 12 weeks. Subjects will be randomized to either the vortioxetine arm (N=15) or placebo arm (N=15). The treatment group will receive vortioxetine 10mg per day, which will be increased to 20 mg or decreased to 5 mg, if deemed clinically necessary, at week 4 or 8. Subjects will have a total of 4-5 visits: Baseline evaluation (1 or 2 visits) and follow-up visits at weeks 4, 8 and 12.
Well-validated psychiatric instruments will be used to compare the effectiveness of vortioxetine versus placebo treatment at week 12 compared to baseline for the treatment of major depression and its neuropsychiatric co-morbidities.
Relevance: This study has the potential to provide strong preliminary evidence for the use of vortioxetine as a safe and novel agent for treatment of TBI depression and its psychiatric co-morbidities. If found to be effective, results from this study can be used to design larger studies and also determine brain changes associated with its use via neuroimaging. Depression is common in other neurological disorders such as stroke, multiple sclerosis, Parkinson's disease, and dementia syndromes. Results from this study can shed light in the management of depression in other neurological disorders.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Drug-Vortioxetine | Experimental | Drug: VortioxetineThe treatment group will receive vortioxetine 10 mg per day, which will be increased to 20 mg or decreased to 5 mg, if deemed clinically necessary, at week 4 or 8. |
| Placebo | Placebo comparator | Drug: PlaceboMatching placebo will be used. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Adults aged 18 and over
- Meet Department of Defense Criteria for TBI
- Meet DSM 5 criteria for major depression
- Score greater than 16 on the HAM D17
- Currently not on any psychotropics for treatment of depression
Key exclusion criteria (5 listed)
- Subjects who are medically or psychiatrically unstable
- Pregnant women
- History of active substance abuse x 1 month
- Other neurological problems, or a diagnosis of schizophrenia, dementia, or bipolar disorder
- Prior treatment with vortioxetine
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: TrintellixThe study drug, vortioxetine received approval from the U.S. Food and Drug Administration (FDA) to treat adults with major depressive disorder. This study is being done to determine its effectiveness in a specialized population, i.e. those who have developed major depression after a traumatic brain injury. As patients who have sustained a TBI are medically fragile and sensitive to side-effects of medications, it is important to test the effectiveness and safety of vortioxetine in this population. | Drug | Drug-Vortioxetine |
| PlaceboAlso: Sugar pillA placebo comparator will be used in one subset of patients. | Drug | Placebo |
Primary outcome
Reduction of depressive symptoms at 12 weeks as assessed by the Hamilton Depression Scale 17 items (HAMD-17)
Time frame: at 12 weeks
Reduction of depressive symptoms at 12 weeks as assessed by the Clinical Global Impression Improvement (CGI-I) scale
Time frame: at 12 weeks
3 secondary outcomes
Comparison of rates and severity of side-effects and adverse effects in subjects in the treatment arm versus placebo at week 1-12
Time frame: Up to 12 weeks
Change from baseline at week 12 on the Columbia-Suicide Severity Rating Scale (C-SSRS)
Time frame: baseline and at 12 weeks
Change from baseline at week 12 on the Arizona Sexual Experience (ASEX) scale
Time frame: baseline and at 12 weeks
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 2 Sep 2016.
- Individual participant dataSharing planned: No. Prior to the initiation of the study, a method will be developed for data collection. Each participant will have a study folder with a unique identifying number to contain the results of study tests and evaluations. Another folder will also be kept that will hold all consent forms and identifying demographic information. The folders will be reviewed monthly for inconsistencies. The data will be entered into a database maintained in the Neuropsychiatry Division of Johns Hopkins Bayview Medical Center, which is password protected and only the PI and her Research team will have access to the study folders and database. The data monitoring committee will include Dr. Rao (PI), and members of the Data \& Safety monitoring board: Drs. Christopher Marano, Paul Rosenberg and Jin Joo. All members of the Diagnostic and Statistical Manual of Mental Disorders (DSM) board are psychiatrists and faculty Johns Hopkins University. The 3 DSM members are not connected with the study.
Related trials for TBI
Active, not recruitingObservational study
Transforming Research and Clinical Knowledge in Traumatic Brain Injury Epileptogenesis Project (TRACK-TBI EPI)
Traumatic Brain Injury, Post-traumatic Epilepsy
Enrolling by invitationPhase 2
Thiotepa + TBI + Fludarabine + Etoposide for Allo-HSCT in Patients With R/R or High-risk Acute Leukemia
Acute Leukemia, High Risk, Acute Leukemia Refractory
Enrolling by invitationPhase 1
Pilot Safety and Exploratory Efficacy of PSC-05 for the Treatment of Chronic Mild Traumatic Brain Injury
Mild Traumatic Brain Injury
RecruitingObservational study
Intracranial Pressure Monitoring in Moderate Traumatic Brain Injury
Moderate Traumatic Brain Injury
Not yet recruitingPhase 1
Nanopulse Laser Therapy
TBI (Traumatic Brain Injury)
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.
Vani Rao, MD principal investigator
Johns University and School of Medicine
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Vortioxetine in people with TBI and Major Depression, run by Johns Hopkins University.
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 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 2 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Reduction of depressive symptoms at 12 weeks as assessed by the Hamilton Depression Scale 17 items (HAMD-17) (time frame: at 12 weeks). 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 2 Sep 2016.