Vortioxetine for Posttraumatic Stress Disorder

Study Overview
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Brief Summary
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Post-traumatic stress disorder (PTSD) can result from having experienced or witnessed a traumatic event. Patients with PTSD symptoms can sometimes experience symptom relief after treatment with antidepressants; however, few patients experience complete symptom relief. There is a need to develop new treatments for PTSD. This study will evaluate if 12 weeks of using Vortioxetine relieves PTSD symptoms. Vortioxetine has been approved for the treatment of depression; however, Vortioxetine has not been approved by the Food and Drug Administration for the treatment of PTSD.

Detailed Description
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Patients included in the study will either take the study medication or will take a placebo, a pill without the active medication. This will be determined by chance like a flip of a coin. Study procedures will include taking study medication and coming to regular in-clinic visits. Depending on the study visit, study tests may include the following: medical evaluations, physical exams, body measurements, vital signs, blood and urine tests, pregnancy tests, genetic testing, heart function monitoring, clinical and psychiatric measures, neuropsychological testing (for example, investigators will test how well you remember words or how fast you perform a certain task), a function test (for example, investigators will test how well you perform certain daily tasks), and a test to measure your startle response. A startle response is an unexpected response by a sudden activity.

Official Title
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Evaluation of the Efficacy of Vortioxetine for Posttraumatic Stress Disorder

Conditions
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Post-Traumatic Stress Disorder

Intervention / Treatment
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* Drug: Placebo
* Drug: Vortioxetine


Participation Criteria
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Eligibility Criteria
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Inclusion Males and Females between the ages of 18 and 65 Fulfills Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for primary diagnosis of PTSD. Able to give consent Willingness to sign the treatment contract A negative urine toxicology For females of reproductive age, use of an effective birth control method* for the duration of the study or abstinence. Duration of illness of PTSD for at least 3 months An initial score at Screening, and Visit 3 (randomization) of ≥ 50 on the Clinician Administered PTSD Scale (CAPS) for PTSD Studies Exclusion Lifetime or current diagnosis of schizophrenia or other psychotic disorder, dementia, bipolar disorder. Subject is currently participating in another clinical trial in which s/he is or will be exposed to an investigational or non-investigational drug or device, or has done so within the preceding month. Current evidence or history of significant unstable medical illness or organic brain impairment, including stroke, Central Nervous System (CNS) tumor, demyelinating disease, cardiac, pulmonary, gastrointestinal, renal or hepatic impairment that would likely interfere with the action, absorption, distribution, metabolism, or excretion of Vortioxetine. History of moderate or more severe Traumatic Brain Injury (TBI) will also be exclusionary. Patients who in the investigator's judgment pose a current suicidal or homicidal risk DSM-5 substance abuse or dependence within the past 90 days. Subject has a positive urine toxicology test for illegal substances. Diagnosis of anorexia nervosa, bulimia, or Obsessive Compulsive Disorder (OCD) in the past year. Subject has a documented history of hepato-biliary disease including a history of, or positive laboratory results for hepatitis (hepatitis B surface antigen and/or hepatitis C antibody), and clinically significant hepatic enzyme elevation, including any one of the following enzymes greater than 3 times the upper limit of normal (ULN) value (Alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase( ALP)), or total or direct bilirubin > 1.5 x ULN, unless consistent with presumed or diagnosed Gilbert's disease Subject has taken systemic corticosteroids within 2 weeks of the Randomization Visit Treatment with any other psychoactive medication within 2 weeks of Visit 1, including all antidepressants, psychoactive herbal or nutritional treatment (St Johns Wort,S-Adenosyl methionine(SAM-e)), lithium, other mood stabilizers, oral antipsychotics, depot antipsychotics within 12 weeks, beta blockers, thioridazine, pimozide, opiates, anxiolytics, and sedatives (with the exception of zolpidem, eszopiclone, and zaleplon). Also any treatment with any medication that the PI judges not acceptable for this study. Pregnancy or lactation* Subjects who, in the opinion of the investigator, would be noncompliant with the visit schedule or study procedures (e.g. illiteracy, planned vacations, or planned hospitalizations during the study). Any laboratory abnormality that in the investigator's judgment is considered to be clinically significant Patients who are receiving exposure-based psychotherapy that targets PTSD symptoms Current or planned litigation or other actions related to secondary gain regarding the traumatic event Subject has clinical evidence of, or ElectroCardiogram (ECG) results indicating any of the following at either screen or Randomization Visit unless repeat ECG shows that the parameter had returned to within normal range by the Randomization Visit: Q to T interval change (QTc)> 450 msec for men, or > 475 msec for women; any cardiac condition or ECG evidence that the investigator feels may pose a potential safety concern.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo pill once daily for 12 weeks of active treatment. | Drug: Placebo<br>* Placebo pill matching Vortioxetine.<br>|
| Active Comparator: Vortioxetine<br>Vortioxetine pill 10mg once daily up to 4 weeks followed by 20mg once daily if tolerated for the rest of the study. Patients unable to tolerate the 20 mg/day dose may be reduced to 10 mg/day between weeks 4 and 8. The dose of study medication should remain stable for weeks 8-12. | Drug: Vortioxetine<br>* Immediate Release 10 mg. Vortioxetine Pill<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change Clinician Administered PTSD Scale Score | Clinician-Administered PTSD Scale (CAPS-5) has a total score ranging from 0-80 with the higher score indicating greater degree of PTSD symptom severity. | Baseline, Up to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants That Achieve Treatment Response Via Clinician Administered PTSD Scale (CAPS)-5 | Number of participants that achieve treatment response will be reported as those that has achieved a 30% improvement in their CAPS-5 total score from baseline. CAPS-5 has a total score ranging from 0-80 with the higher score indicating greater degree of PTSD symptom severity. Observed cases only. | Week 12 | 
| Change in Depressive Symptoms in PTSD | Montgomery-Asberg Depression Rating Scale (MADRS) has a total score ranging from 0-60, with 0 meaning no depressive symptoms and 60 meaning severe depressive symptoms.(MADRS). From the total score 0-60, with 0 meaning no depressive symptoms and 60 meaning severe depressive symptoms. | Baseline, Up to Week 12 | 
| Number of Participants That Achieve Treatment Response Via CGI-I | Clinical Global Impression of Improvement (CGI-I) is a 7 point Likert-scale questionnaire assessing PTSD symptoms improvement. A score of 1 indicates very much improved, 4 indicates no change and 7 indicates much worse. Treatment response will be reported as the number of participants with an improvement of 1-2 points on their CGI-I score from baseline. Analysis includes observed cases only. | Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PTSD,, trauma, stress disorder, post-traumatic stress disorder, anxiety disorder