Vortioxetine for the Treatment of Major Depression and Co-morbidities After Traumatic Brain Injury (TBI)

NCT02845349 | Withdrawn Phase 3 DMC

• 1 other identifier: IRB00105196
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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. 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.

Conditions

TBI; Major Depression

Outcome Measures

Primary Outcomes (2)

• Reduction of depressive symptoms at 12 weeks as assessed by the Hamilton Depression Scale 17 items (HAMD-17)

  at 12 weeks

• Reduction of depressive symptoms at 12 weeks as assessed by the Clinical Global Impression Improvement (CGI-I) scale

  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

  Up to 12 weeks

• Change from baseline at week 12 on the Columbia-Suicide Severity Rating Scale (C-SSRS)

  baseline and at 12 weeks

• Change from baseline at week 12 on the Arizona Sexual Experience (ASEX) scale

  baseline and at 12 weeks

Other Outcomes (7)

• Reduction of anxiety symptoms at 12 weeks as assessed by the Generalized Anxiety Disorder-7-item (GAD-)

  at 12

• Reduction of post traumatic stress symptoms at 12 weeks as assessed by the Post traumatic stress disorder Checklist for DSM-5 (PCL-5)

  at 12 weeks

• Improvement in sleep symptoms at 12 weeks as assessed by the Pittsburgh Sleep Quality Index (PSQI)

  at 12 weeks

Study Arms (2)

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.

Drug: Vortioxetine

Placebo

PLACEBO COMPARATOR

Matching placebo will be used.

Drug: Placebo

Interventions

Vortioxetine DRUG

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.

Also known as: Trintellix

Drug-Vortioxetine

Placebo DRUG

A placebo comparator will be used in one subset of patients.

Also known as: Sugar pill

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Johns Hopkins University: lead
• Takeda: collaborator

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Vortioxetine; Sugars

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Carbohydrates

Study Officials

• Vani Rao, MD

  Johns University and School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 18, 2016
• First Posted: July 27, 2016
• Study Start: October 1, 2016
• Primary Completion: October 1, 2018
• Study Completion: October 1, 2018
• Last Updated: September 2, 2016

Record last verified: 2016-09

Data Sharing

• IPD Sharing: Will not share