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

NCT02749721 | Completed Phase 4 Results FDA Drug

• 1 other identifier: IISR-2014-100702a
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 2

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.

Conditions

Major Depressive Disorder

Keywords

depression; brain network activation; vortioxetine

Outcome Measures

Primary Outcomes (4)

• Change in Montgomery and Asberg Depression Rating Scale (MADRS)

  The MADRS is a 10-item rating scale designed to assess the severity of symptoms of depression. Range is 0-60. Higher score means more severe.

  from baseline to endpoint (up to 8 weeks)

• Change From Baseline to Endpoint in Digital Symbol Substitution Test.

  Change in cognitive function defined as change from baseline to endpoint. The Digital Symbol Substitution Test (DSST) is a cognitive test designed to assess psychomotor speed of performance requiring visual perception, spatial decision-making and motor skills. The DSST consists of 133 digits and requires the subject to substitute each digit with a simple symbol in a 90-second period. The number of correct symbols within the allowed time (eg, 90 sec) is measured. It takes approximately 5 minutes to complete and score the DSST.

  Baseline to endpoint (week 8)

• BNA Scores Amplitudes

  Brain Network Analytics (BNA) is a tool intended for the post-hoc statistical analysis of the human EEG, utilizing both resting-state EEG and event-related potentials (ERP) waveforms. The BNA algorithm compares a patient's ERP amplitudes and latencies to those of a large group of healthy, age-matched subjects in order to visualize and quantify changes in specific brain functions. The BNA algorithm was used to detect subjects' P200 and P300 ERP components from EEG data recorded during the AOB and VGNG tasks. BNA scores represent these ERP components in terms of amplitude (in microvolts) and latency (in milliseconds).

  Baseline to Endpoint (8 weeks)

• BNA Scores Latencies

  Brain Network Analytics (BNA) is a tool intended for the post-hoc statistical analysis of the human EEG, utilizing both resting-state EEG and event-related potentials (ERP) waveforms. The BNA algorithm compares a patient's ERP amplitudes and latencies to those of a large group of healthy, age-matched subjects in order to visualize and quantify changes in specific brain functions. The BNA algorithm was used to detect subjects' P200 and P300 ERP components from EEG data recorded during the AOB and VGNG tasks. BNA scores represent these ERP components in terms of amplitude (in microvolts) and latency (in milliseconds).

  Baseline to Endpoint (8 weeks)

Secondary Outcomes (6)

• Changes in Hamilton Depression Rating Scale (HDRS) 17 From Baseline to 8 Week Endpoint

  Baseline to endpoint (week 8)

• Changes in Hamilton Depression Rating Scale (HDRS) 28 From Baseline to 8 Week Endpoint

  Baseline to endpoint (week 8)

• Changes in Quick Inventory of Depressive Symptomatology - Self-Report (QIDS-16-SR) From Baseline to 8 Week Endpoint

  Baseline to endpoint (week 8)

• Changes in Clinical Global Impression Scale (CGI-S) From Baseline to 8 Week Endpoint

  Baseline to endpoint (week 8)

• Correlations Between BNA Amplitude Scores and Clinical, Cognitive, and Functionality Assessments Using Baseline Scores

  Baseline to Endpoint (8 weeks)

Study Arms (1)

Other - vortioxetine

OTHER

Open-label vortioxetine

Drug: vortioxetine

Interventions

vortioxetine DRUG

Open-label vortioxetine

Other - vortioxetine

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Rush University Medical Center: lead
• Takeda Pharmaceuticals North America, Inc.: collaborator
• ElMindA Ltd: collaborator

Study Sites (2)

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Rush University Medical Center

Skokie, Illinois, 60076, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Major; Depression

Interventions

Vortioxetine

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

Secondary outcomes #4 and #7, part c were not included in the results section for the following reasons: analysis became too complex based on low sample size; too many subgroups were needed. There were changes in BNA regardless of changes in symptoms and couldn't isolate meaningful or clinical useful data. In addition, several cognitive and functionality scores (i.e., CGI-I, TMT, UPSA, Stroop) were not collected at baseline and therefore not included in the "correlation with BNA" analysis.

Results Point of Contact

• Title: Dr. John Zajecka
• Organization: Rush University Medical Center

John_Zajecka@rush.edu

312-942-5592

Study Officials

• John M Zajecka, MD

  Rush University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2016
• First Posted: April 25, 2016
• Study Start: December 1, 2016
• Primary Completion: January 31, 2019
• Study Completion: January 31, 2019
• Last Updated: October 4, 2021
• Results First Posted: October 4, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)