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The Relationship Among Changes in Brain Network Activation in Adult Outpatients With Major Depressive Disorder

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ClinicalTrials.gov Identifier: NCT02749721
Recruitment Status : Recruiting
First Posted : April 25, 2016
Last Update Posted : March 30, 2018
Sponsor:
Collaborators:
Takeda Pharmaceuticals North America, Inc.
ElMindA Ltd
Information provided by (Responsible Party):
Rush University Medical Center

Brief Summary:
The purpose of this study is to explore patterns of Brain Network Activation (BNA) changes from baseline to endpoint on 1) efficacy of core symptoms of Major Depressive Disorder (MDD) and 2) improvement of cognitive dysfunction with acute treatment with flexible dose vortioxetine in adult outpatients with MDD and subjective complaints of cognitive dysfunction.

Condition or disease Intervention/treatment Phase
Major Depressive Disorder Drug: vortioxetine Phase 4

Detailed Description:

Vortioxetine is a novel antidepressant with hypothetical multimodal mechanism of action. It is thought to work through a combination of multiple pharmacological modes of action: 5-HT (hydroxytryptamine, or serotonin) reuptake inhibition, 5-HT3 (hydroxytryptamine, or serotonin) and 5-HT7 (hydroxytryptamine, or serotonin) receptor antagonism, 5-HT1A (hydroxytryptamine, or serotonin) receptor agonism, and 5-HT1B (hydroxytryptamine, or serotonin) receptor partial agonism. In vivo nonclinical studies have demonstrated that vortioxetine enhances levels of the neurotransmitters 5-HT (hydroxytryptamine, or serotonin), norepinephrine (NE), dopamine (DA), acetylcholine and histamine in specific areas of the brain. These affinities are all considered to be of clinical relevance and involved in the mechanism of action at therapeutic doses.

Vortioxetine has been shown to improve core depressive symptoms and improve cognitive function in adult outpatients with MDD and subjective complaints of cognitive function. This pilot study is intended to evaluate the extent to which BNA technology can provide clinically valuable information and provide information toward designing a subsequent confirmatory study that will further elucidate the effect of vortioxetine on MDD and cognitive function in this population. This exploratory study will ascertain the acute changes in core depression symptoms, cognitive function, tolerability, and safety using flexible-dose vortioxetine in adult outpatients with MDD with subjective complaints of cognitive functioning, as measured by BNA changes and standard outcome measures for depression and cognition.

The study consists of 8 weeks of open-label treatment for MDD with response to treatment measured by standard research depression scales and BNA electroencephalogram (EEG) readings taken at certain points during the trial. An important aim in this study is to explore what correlations may exist between changes in measured brainwave patterns and reported change in depressive symptoms


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Relationship Among Changes in Brain Network Activation, Changes in Core Depressive and Cognitive Symptoms and Safety and Tolerability in Adults With Major Depressive Disorder Treated With Open-Label, Flexible-Dose Vortioxetine
Study Start Date : December 2016
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : February 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Open-label vortioxetine Drug: vortioxetine



Primary Outcome Measures :
  1. Change in Montgomery and Asberg Depression Rating Scale (MADRS) [ Time Frame: from baseline to endpoint (up to 8 weeks) ]
    The MADRS is a 10-item rating scale designed to assess the severity of symptoms of depression.



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • The subject has single episode or recurrent MDD (acute onset of recurrence of recurrent MDD with poor inter-episode recovery) (inter-episode periods cannot meet full MDD criteria) as the primary diagnosis according to DSM-IV-TR criteria. The current major depressive episode (MDE) will be confirmed using the Mini International Neuropsychiatric Interview (MINI V6.0.0).
  • The subject has a MADRS total score ≥26.
  • Subject reports subjective cognitive dysfunction (such as difficulty concentrating, slow thinking, and difficulty in learning new things or remembering things).
  • The reported duration of the current MDE is at least 3 months and no longer than 24 months.
  • The subject is a man or woman between 18 and 65 years old, inclusive.
  • Right-handed, normal (corrected) vision, and normal hearing.

Exclusion Criteria:

  • The subject has a score of ≥70 on the Digit Symbol Substitution Test (DSST) at the Baseline Visit.
  • Failure to respond to or inability to tolerate an adequate trial of vortioxetine in the past.
  • Exposure to an investigational compound 30 days prior to enrollment
  • Exposure to any psychoactive or otherwise excluded medication within five half-lives of the baseline visit or during the study. Excluded medications include: antidepressants, anxiolytics, anticonvulsants, barbiturates, chloral hydrate, lithium, antipsychotics, benzodiazepines, hypnotics, monoamine oxidase inhibitors (MAOIs), muscle relaxers, triptans, centrally-acting antihistamines, central alpha-2 agonists, decongestants, psychostimulants, dopamine agonists, opioid pain medications, oral corticosteroids, L-methylfolate, S-adenosyl methionine (SAMe), 5-HTP (hydroxytryptophan), St. John's Wort,
  • The subject has 1 or more of the following:

    • Primary psychiatric disorder other than MDD as defined in the Diagnostic and Statistical Manual of Mental Disorders 4 Text Revision (DSM-IV-TR) (as assessed by the MINI, Version 6.0.0).
    • Current or history of attention deficit hyperactivity disorder (ADHD), pervasive developmental disorder, manic or hypomanic episode, schizophrenia, or any other psychotic disorder, including major depression with psychotic features, mental retardation, organic mental disorders, or mental disorders due to a general medical condition as defined in the DSM-IV-TR.
    • Current diagnosis of alcohol or other substance abuse or dependence (excluding nicotine or caffeine) as defined in the DSM-IV-TR that has not been in sustained full remission for at least 6 months (for abuse) and 12 months (for dependence) prior to Screening.
    • Positive urine drug screen prior to Baseline.
    • Presence or history of a clinically significant neurological disorder (including epilepsy).
    • Neurodegenerative disorder (Alzheimer Disease, Parkinson Disease, multiple sclerosis, Huntington Disease, etc).
    • Any unstable medical condition as determined by the principal investigator (PI).
    • Any DSM-IV Axis II disorder that might compromise the study as determined by the PI.
  • The subject has any other disorder for which the treatment takes priority over treatment of MDD or is likely to interfere with study treatment or impair treatment compliance.
  • The subject has physical, cognitive, or language impairment of such severity as to adversely affect the validity of the data derived from the neuropsychological tests.
  • The subject has a significant risk of suicide according to the PI's clinical judgment.
  • The subject, in the opinion of the PI, poses a risk of harm to others.
  • The subject has initiated formal cognitive or behavioral therapy, systemic psychotherapy within less than 6 months of study screening, or has plans to initiate such therapy during the study.
  • The subject has received electroconvulsive therapy, vagus nerve stimulation, or repetitive transcranial magnetic stimulation within 12 months prior to Screening.
  • The current MDE is considered by the PI to have been resistant to 2 adequate antidepressant treatments of at least 6 weeks duration each at the recommended dose.
  • The subject is pregnant or breastfeeding, or is intending to become pregnant before, during, or within 30 days after participating in this study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02749721


Contacts
Contact: Linda M Skaggs 312-942-5592 linda_m_skaggs@rush.edu
Contact: John M Zajecka, MD 312-942-5592 john_zajecka@rush.edu

Locations
United States, Illinois
Rush University Medical Center Recruiting
Chicago, Illinois, United States, 60612
Contact: Linda Skaggs    312-942-5592    linda_skaggs@rush.edu   
Contact: Karen Neimanas    312-563-2595    karen_neimanas@rush.edu   
Principal Investigator: John Zajecka, MD         
Sub-Investigator: Corey Goldstein, MD         
Rush University Medical Center Recruiting
Skokie, Illinois, United States, 60076
Contact: Linda Skaggs    312-942-5592    linda_skaggs@rush.edu   
Contact: Karen Neimanas    312-563-2595    karen_neimanas@rush.edu   
Sponsors and Collaborators
Rush University Medical Center
Takeda Pharmaceuticals North America, Inc.
ElMindA Ltd
Investigators
Principal Investigator: John M Zajecka, MD Rush University Medical Center

Responsible Party: Rush University Medical Center
ClinicalTrials.gov Identifier: NCT02749721     History of Changes
Obsolete Identifiers: NCT02559947
Other Study ID Numbers: IISR-2014-100702a
First Posted: April 25, 2016    Key Record Dates
Last Update Posted: March 30, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Rush University Medical Center:
depression
brain network activation
vortioxetine

Additional relevant MeSH terms:
Disease
Depressive Disorder
Depression
Depressive Disorder, Major
Pathologic Processes
Mood Disorders
Mental Disorders
Behavioral Symptoms
Vortioxetine
Anti-Anxiety Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Serotonin Agents
Serotonin 5-HT1 Receptor Agonists
Serotonin Receptor Agonists
Serotonin 5-HT1 Receptor Antagonists
Serotonin Antagonists
Serotonin 5-HT3 Receptor Antagonists