Vortioxetine for Posttraumatic Stress Disorder

• Sponsor: University of Miami (Other)
• Overall Status: Completed
• CT.gov ID: NCT02637895
• Collaborator: Takeda (Industry), Emory University (Other)
• Enrollment: 41
• Locations: 2
• Arms: 2
• Actual Duration (Months): 38.2
• Patients Per Site: 20.5
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Post-Traumatic Stress Disorder	Drug: Placebo; Drug: Vortioxetine	Phase 4

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 41 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Evaluation of the Efficacy of Vortioxetine for Posttraumatic Stress Disorder
• Actual Study Start Date: Dec 1, 2016
• Actual Primary Completion Date: Jan 22, 2020
• Actual Study Completion Date: Feb 6, 2020

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Placebo pill once daily for 12 weeks of active treatment.	Drug: Placebo; Placebo pill matching Vortioxetine.
Active Comparator: Vortioxetine 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; Immediate Release 10 mg. Vortioxetine Pill

Outcome Measures

Primary Outcome Measures

1. Change Clinician Administered PTSD Scale Score [Baseline, Up to Week 12]

   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.

Secondary Outcome Measures

1. Number of Participants That Achieve Treatment Response Via Clinician Administered PTSD Scale (CAPS)-5 [Week 12]

   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.

2. Change in Depressive Symptoms in PTSD [Baseline, Up to Week 12]

   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.

3. Number of Participants That Achieve Treatment Response Via CGI-I [Week 12]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion

1. Males and Females between the ages of 18 and 65

2. Fulfills Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for primary diagnosis of PTSD.

3. Able to give consent

4. Willingness to sign the treatment contract

5. A negative urine toxicology

6. For females of reproductive age, use of an effective birth control method* for the duration of the study or abstinence.

7. Duration of illness of PTSD for at least 3 months

8. An initial score at Screening, and Visit 3 (randomization) of ≥ 50 on the Clinician Administered PTSD Scale (CAPS) for PTSD Studies

Exclusion

1. Lifetime or current diagnosis of schizophrenia or other psychotic disorder, dementia, bipolar disorder.

2. 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.

3. 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.

4. Patients who in the investigator's judgment pose a current suicidal or homicidal risk

5. DSM-5 substance abuse or dependence within the past 90 days. Subject has a positive urine toxicology test for illegal substances.

6. Diagnosis of anorexia nervosa, bulimia, or Obsessive Compulsive Disorder (OCD) in the past year.

7. 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

8. Subject has taken systemic corticosteroids within 2 weeks of the Randomization Visit

9. 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.

10. Pregnancy or lactation*

11. 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).

12. Any laboratory abnormality that in the investigator's judgment is considered to be clinically significant

13. Patients who are receiving exposure-based psychotherapy that targets PTSD symptoms

14. Current or planned litigation or other actions related to secondary gain regarding the traumatic event

15. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Miami	Miami	Florida	United States	33136
2	Emory University	Atlanta	Georgia	United States	30322

Sponsors and Collaborators

• University of Miami
• Takeda
• Emory University

Investigators

• Principal Investigator: Philip Harvey, PhD, University of Miami

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 22, 2019

More Information

Publications

None provided.

• Responsible Party: Philip D. Harvey, Professor, University of Miami
• ClinicalTrials.gov Identifier: NCT02637895
• Other Study ID Numbers: 20150534
• First Posted: Dec 22, 2015
• Last Update Posted: Feb 8, 2021
• Last Verified: Jan 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Philip D. Harvey, Professor, University of Miami: PTSD,; trauma; stress disorder; post-traumatic stress disorder; anxiety disorder
• Additional relevant MeSH terms: Disease; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Vortioxetine

Study Results

Participant Flow

Arm/Group Title	Placebo	Vortioxetine
Arm/Group Description	Placebo pill once daily for 12 weeks of active treatment. Placebo: Placebo pill matching Vortioxetine.	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. Vortioxetine: 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.
Period Title: Overall Study
STARTED	21	20
COMPLETED	15	17
NOT COMPLETED	6	3

Baseline Characteristics

Arm/Group Title	Placebo	Vortioxetine	Total
Arm/Group Description	Placebo pill once daily for 12 weeks of active treatment. Placebo: Placebo pill matching Vortioxetine.	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. Vortioxetine: 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.	Total of all reporting groups
Overall Participants	21	20	41
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	40.1 (11.0)	44.3 (11.9)	42.2 (11.4)
Sex: Female, Male (Count of Participants)
Female	14 66.7%	14 70%	28 68.3%
Male	7 33.3%	6 30%	13 31.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	5 23.8%	4 20%	9 22%
Not Hispanic or Latino	16 76.2%	16 80%	32 78%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	2 9.5%	2 10%	4 9.8%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	9 42.9%	9 45%	18 43.9%
White	10 47.6%	9 45%	19 46.3%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Change Clinician Administered PTSD Scale Score
Description	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.
Time Frame	Baseline, Up to Week 12

Outcome Measure Data

Analysis Population Description

Mixed Model Repeated Measures (MMRM) Analysis of all Intent To Treat (ITT) cases

Arm/Group Title	Placebo	Vortioxetine
Arm/Group Description	Placebo pill once daily for 12 weeks of active treatment. Placebo: Placebo pill matching Vortioxetine.	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. Vortioxetine: 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.
Measure Participants	21	20
Mean (Standard Error) [score on a scale]	16 (3.00)	17 (2.70)

2. Secondary Outcome

Title	Number of Participants That Achieve Treatment Response Via Clinician Administered PTSD Scale (CAPS)-5
Description	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.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Vortioxetine
Arm/Group Description	Placebo pill once daily for 12 weeks of active treatment. Placebo: Placebo pill matching Vortioxetine.	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. Vortioxetine: 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.
Measure Participants	15	17
Count of Participants [Participants]	9 42.9%	11 55%

3. Secondary Outcome

Title	Change in Depressive Symptoms in PTSD
Description	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.
Time Frame	Baseline, Up to Week 12

Outcome Measure Data

Analysis Population Description

Mixed Model Repeated Measures (MMRM) Analysis of all Intent To Treat (ITT) cases

Arm/Group Title	Placebo	Vortioxetine
Arm/Group Description	Placebo pill once daily for 12 weeks of active treatment. Placebo: Placebo pill matching Vortioxetine.	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. Vortioxetine: Immediate Release 10 mg. Vortioxetine Pill
Measure Participants	21	20
Mean (Standard Error) [score on a scale]	9.73 (1.95)	12.06 (2.27)

4. Secondary Outcome

Title	Number of Participants That Achieve Treatment Response Via CGI-I
Description	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.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Vortioxetine
Arm/Group Description	Placebo pill once daily for 12 weeks of active treatment. Placebo: Placebo pill matching Vortioxetine.	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. Vortioxetine: 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.
Measure Participants	15	17
Count of Participants [Participants]	10 47.6%	11 55%

Adverse Events

Time Frame	16 weeks
Adverse Event Reporting Description	Only treatment-related adverse events, as evaluated by treating physician, will be reported at the 5% reporting threshold.
Arm/Group Title	Placebo		Vortioxetine
Arm/Group Description	Placebo pill once daily for 12 weeks of active treatment. Placebo: Placebo pill matching Vortioxetine.		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. Vortioxetine: 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.
All Cause Mortality
	Placebo		Vortioxetine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		0/20 (0%)
Serious Adverse Events
	Placebo		Vortioxetine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		0/20 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Vortioxetine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/21 (52.4%)		15/20 (75%)
Gastrointestinal disorders
Diarrhea	4/21 (19%)	10	3/20 (15%)	4
Constipation	2/21 (9.5%)	3	4/20 (20%)	5
Nausea	4/21 (19%)	6	10/20 (50%)	16
General disorders
Headache	4/21 (19%)	11	6/20 (30%)	10

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.