Clinical trial NCT03053362: THINC-it Vortioxetine - Sensitivity to Change
Official title: An Open-Label Clinical Trial Evaluating Sensitivity to Change in Cognition Using the THINC-it Following Treatment With Vortioxetine in Major Depressive Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Major Depressive Disorder
Cognitive Change
Lead sponsor: Brain and Cognition Discovery Foundation
Sponsor class: OTHER
First posted: 2017-02-15
Enrollment: 158
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Determining the effectiveness of a new tool used to detect changes in cognition among individuals with MDD.
Primary purpose: OTHER

Brief summary: The purpose of this study is to evaluate the sensitivity of the THINC-it tool, in measuring change in cognitive deficits in individuals with MDD after receiving vortioxetine.

Detailed description: Vortioxetine is used in this study as an antidepressant to improve mood, cognition and quality of life. "Cognition" refers to intellectual functions such as thinking, understanding, learning and remembering. Vortioxetine is approved by Health Canada for the treatment of MDD. In addition, vortioxetine has been reported to have a beneficial effect on cognitive areas such as executive function, attention/speed of processing, and memory, that are commonly affected negatively by MDD. Vortioxetine is recognized by Health Authorities in the EU and many other countries as having a benefit on cognitive dysfunction (loss of intellectual functions) in patients with MDD.Cognitive dysfunction is a highly persistent, pervasive and progressive abnormality in young adults (i.e., 18-65 years) with MDD.

It has also been shown that among adults with MDD who are gainfully employed, measures of cognition are a greater determinant of overall workplace performance than is total depression symptom severity. Several lines of evidence indicate that cognitive deficits that persist between episodes of depression are critical determinants of functional recovery in the workplace. The functional implications associated with cognitive impairment provide the impetus for systematic evaluation, measurement and assessment of the domains of cognition expected to be impaired in this patient population.

To date, no measurement tool has been sufficiently validated and/or determined to be sensitive to the cognitive deficits in younger adults with MDD. Major limitations of available comprehensive psychometric tools include relative lack of availability, cost, lack of access to most healthcare providers, and above all else, the lengthy time to administer. Moreover, the need for a psychometrist to interpret the results adds to the complexity and the costliness of such an endeavor.

It is imperative that any tool recommended for clinical utility be aligned with the busy nature of a high-volume clinical practice. The ideal gold standard tool for assessing the presence of cognitive dysfunction in MDD in the clinical environment should include, but not be limited to, features such as good conceptual coverage of cognitive domains affected in MDD, good sensitivity and reliability, and it should be relatively uninfluenced by culture effects and practice effects. The tool would also need to be brief, easy to administer and interpret, and complement busy clinical practice.

It is anticipated that the THINC-it tool will be free of charge and downloadable from the THINC-it website for use in the primary care and specialty setting. The THINC-it tool will be accessible via computers/tablets, will take 20 minutes to self-administer in a clinical setting, and the performance results will be immediately available.

Eligibility criteria: MDD Population

Inclusion Criteria:

1. The participant is able and willing to provide informed consent.
2. The participant is male or female 18-65 years of age.
3. The participant has received a current diagnosis of a major depressive episode (MDE) as part of MDD as per DSM-5 criteria.
4. The participant's current MDE is confirmed by the Mini International Neuropsychiatric Interview (M.I.N.I 5.0.).
5. The participant is an outpatient of a psychiatric setting.
6. The participant has a MADRS score ≥ 26 at screening and baseline.
7. The participant's reported duration of the current MDE is at least 3 months.
8. At least one prior major depressive episode validated by previous treatment (e.g., guideline-informed pharmacotherapy and/or manual-based psychotherapy).
9. All participants will be screened for cognitive impairment based on DSST performance (pen-and-paper version) with a maximum baseline score of 70 correct symbols entered to avoid ceiling effects.

Exclusion Criteria:

1. Current alcohol and/or substance use disorder.
2. Presence of comorbid psychiatric disorder other than MDD that is a focus of clinical concern as confirmed by the M.I.N.I 5.0.
3. Medications approved and/or employed off-label for cognitive dysfunction (e.g., psychostimulants).
4. Any medication for a general medical disorder that, in the opinion of the investigator, may affect cognitive function (e.g., corticosteroids, beta-blockers).
5. Use of benzodiazepines within 12 hours of cognitive assessments.
6. Consumption of alcohol within 8 hours of cognitive assessments.
7. Recent use of marijuana as determined by a toxicology screen.
8. Physical, cognitive, or language impairments sufficient to adversely affect data derived from cognitive assessments.
9. Diagnosis reading disability or dyslexia.
10. Clinically significant learning disorder by history.
11. Electroconvulsive therapy (ECT) in the last 6 months.
12. History of moderate or severe head trauma (e.g., loss of consciousness for \>1 hour), other neurological disorders, or unstable systemic medical diseases that in the opinion of the investigator are likely to affect the central nervous system.
13. Pregnant and/or breastfeeding.
14. Received investigational agents as part of a separate study within 30 days of the screening visit.
15. Actively suicidal or evaluated as being a suicide risk (a score of \> 4 on the MADRS and/or per clinical judgment using the Columbia-Suicide Severity Rating Scale).
16. Currently receiving treatment with Monoamine Oxidase Inhibitors (MAOIs) anti-depressants, antibiotics such as linezolid, or intravenous methylene blue.

Healthy Control Population

Inclusion Criteria:

1. No current or past history of mental disorder as evidenced by the M.I.N.I. 5.0 for DSM-IV.
2. No first-degree relative with an established diagnosis by a healthcare provider of a mood or psychiatric disorder.
3. No unstable medical disorders.

Exclusion Criteria:

1. Use of any medication for a general medical disorder and/or condition that, in the opinion of the investigator, may affect cognitive function (e.g., corticosteroids, beta-blockers).
2. Pregnant and/or breastfeeding.
3. Consumption of alcohol within 8 hours of THINC-it tool administration.
4. Recent use of marijuana as determined by a toxicology screen.

Primary outcomes:
measure: Cognition Measured Using the THINC-it Tool
timeFrame: Baseline and 8 weeks
Secondary outcomes:
measure: Changes in Mood as Measured by the Montgomery Åsberg Depression Rating Scale (MADRS)
timeFrame: Baseline and 8 weeks
measure: Changes in Cognitive Function Assessed by the Digit Symbol Substitution Task (DSST)
timeFrame: Baseline and 8 weeks
measure: Changes in Cognitive Function Assessed by the Trail Making Test - Part B (TMT-B)
timeFrame: Baseline and 8 weeks
measure: Changes in Global Functional Impairment Using the Sheehan Disability Scale Total Score
timeFrame: Baseline and 8 weeks
measure: Changes in the World Health Organization Wellbeing Index (5-Item)
timeFrame: Baseline and 8 weeks
measure: Changes in Changes in Anhedonia From Baseline to Week 8
timeFrame: Baseline and 8 weeks
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: CRTCE/KJK Healthplex
state: Ontario
Study officials:
affiliation: Brain and Cognition Discovery Foundation
name: Roger McIntyre
role: PRINCIPAL_INVESTIGATOR
References:
citation: McIntyre RS, Subramaniapillai M, Park C, Zuckerman H, Cao B, Lee Y, Iacobucci M, Nasri F, Fus D, Bowie CR, Tran T, Rosenblat JD, Mansur RB. The THINC-it Tool for Cognitive Assessment and Measurement in Major Depressive Disorder: Sensitivity to Change. Front Psychiatry. 2020 Jun 24;11:546. doi: 10.3389/fpsyt.2020.00546. eCollection 2020.
citation: Subramaniapillai M, Mansur RB, Zuckerman H, Park C, Lee Y, Iacobucci M, Cao B, Ho R, Lin K, Phan L, McIntyre RS. Association between cognitive function and performance on effort based decision making in patients with major depressive disorder treated with Vortioxetine. Compr Psychiatry. 2019 Oct;94:152113. doi: 10.1016/j.comppsych.2019.07.006. Epub 2019 Jul 24.
citation: Cao B, Park C, Subramaniapillai M, Lee Y, Iacobucci M, Mansur RB, Zuckerman H, Phan L, McIntyre RS. The Efficacy of Vortioxetine on Anhedonia in Patients With Major Depressive Disorder. Front Psychiatry. 2019 Jan 31;10:17. doi: 10.3389/fpsyt.2019.00017. eCollection 2019.