Back to resultsTHINC-it Vortioxetine - Sensitivity to Change
Primary Purpose
Major Depressive Disorder, Cognitive Change
Status
Completed
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Vortioxetine
THINC-it Tool
Sponsored by
About this trial
This is an interventional other trial for Major Depressive Disorder
Eligibility Criteria
MDD Population
Inclusion Criteria:
- The participant is able and willing to provide informed consent.
- The participant is male or female 18-65 years of age.
- The participant has received a current diagnosis of a major depressive episode (MDE) as part of MDD as per DSM-5 criteria.
- The participant's current MDE is confirmed by the Mini International Neuropsychiatric Interview (M.I.N.I 5.0.).
- The participant is an outpatient of a psychiatric setting.
- The participant has a MADRS score ≥ 26 at screening and baseline.
- The participant's reported duration of the current MDE is at least 3 months.
- At least one prior major depressive episode validated by previous treatment (e.g., guideline-informed pharmacotherapy and/or manual-based psychotherapy).
- 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:
- Current alcohol and/or substance use disorder.
- 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.
- Medications approved and/or employed off-label for cognitive dysfunction (e.g., psychostimulants).
- Any medication for a general medical disorder that, in the opinion of the investigator, may affect cognitive function (e.g., corticosteroids, beta-blockers).
- Use of benzodiazepines within 12 hours of cognitive assessments.
- Consumption of alcohol within 8 hours of cognitive assessments.
- Recent use of marijuana as determined by a toxicology screen.
- Physical, cognitive, or language impairments sufficient to adversely affect data derived from cognitive assessments.
- Diagnosis reading disability or dyslexia.
- Clinically significant learning disorder by history.
- Electroconvulsive therapy (ECT) in the last 6 months.
- 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.
- Pregnant and/or breastfeeding.
- Received investigational agents as part of a separate study within 30 days of the screening visit.
- 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).
- Currently receiving treatment with Monoamine Oxidase Inhibitors (MAOIs) anti-depressants, antibiotics such as linezolid, or intravenous methylene blue.
Healthy Control Population
Inclusion Criteria:
- No current or past history of mental disorder as evidenced by the M.I.N.I. 5.0 for DSM-IV.
- No first-degree relative with an established diagnosis by a healthcare provider of a mood or psychiatric disorder.
- No unstable medical disorders.
Exclusion Criteria:
- 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).
- Pregnant and/or breastfeeding.
- Consumption of alcohol within 8 hours of THINC-it tool administration.
- Recent use of marijuana as determined by a toxicology screen.
Sites / Locations
- CRTCE/KJK Healthplex
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Other
Arm Label
Major Depressive Disorder Population
Healthy Control Population
Arm Description
100 Individuals with DSM-5-defined MDD, aged 18-65 All participants receiving vortioxetine for a total of 8 weeks. Participants will receive10 mg/day on days 1-14 of the study treatment period, with the option to increase to vortioxetine 20 mg/day at the end of Week 2 based on physician's judgment. For the remaining 6 weeks, the dose of vortioxetine will be flexible at 10 or 20 mg/day as decided by a research doctor. Patients will receive the THINC-it over 3 time frame periods. The THINC-it comprised of: Spotter, Symbol Check, Codebreaker, Trails, and PDQ-5-D.
50 Healthy Controls (18-65 years of age) matched on sex, age, and years of education
Outcomes
Primary Outcome Measures
Cognition Measured Using the THINC-it Tool
Change in cognition as measured by the objective assessments of cognition within the THINC-it tool. "THINC-it" is the name of the cognition tool and is not an acronym. The objective measurements that comprise the THINC-it tool include the Spotter task (Choice Reaction Time), Symbol Check task(1-back test),Trails task(Trails Making Test B), and Codebreaker task (Digit Symbol Substitution Test). The composite score from all four tests were converted to standard z-score. Higher z-scores indicate better cognition. A z-score of zero indicates population mean.
Secondary Outcome Measures
Changes in Mood as Measured by the Montgomery Åsberg Depression Rating Scale (MADRS)
Changes in mood assessed by the Montgomery Åsberg Depression Rating Scale [MADRS]. The overall score ranges from 0 to 60, where greater scores indicate worse depression.
Changes in Cognitive Function Assessed by the Digit Symbol Substitution Task (DSST)
Changes in cognition assessed by the Digit Symbol Substitution Task (DSST). The outcome measure is the number of correct symbols copied by the participants. Higher scores indicate better performance (minimum score is 0 and maximum is 133).
Changes in Cognitive Function Assessed by the Trail Making Test - Part B (TMT-B)
Changes in cognition assessed by the TMT-B. The outcome measure is time in seconds, where greater time indicates worse performance.
Changes in Global Functional Impairment Using the Sheehan Disability Scale Total Score
Sheehan Disability Scale rates the extent to which his or her 1) work, 2) social life or leisure activities, and 3) home life or family responsibilities are impaired by his or her symptoms on a 10-point visual analog scale. The numerical ratings of 0-10 can be translated into a percentage if desired. The three items may be summed into a single dimensional measure of global functional impairment that ranges from 0 (unimpaired) to 30 (highly impaired).
Changes in the World Health Organization Wellbeing Index (5-Item)
The WHO-5 is a short questionnaire consisting of 5 simple and non-invasive questions, which tap into the subjective well-being of the respondents. The WHO-5 only contains positively phrased items. The respondent is asked to rate how well each of the 5 statements applies to him or her when considering the last 14 days. Each of the 5 items is scored from 5 (all of the time) to 0 (none of the time). The raw score therefore theoretically ranges from 0 (absence of well-being) to 25 (maximal well-being). A percent score out of 25 is reported.
Changes in Changes in Anhedonia From Baseline to Week 8
To establish sensitivity to change in anhedonia using the Snaith-Hamilton Pleasure Scale (SHAPS) total score in adults (18-65) with MDD treated with vortioxetine (10-20 mg flexibly dosed for 8 weeks). Higher score indicates more pleasure, with maximum of 56 points on the scale.
Full Information
NCT ID
NCT03053362
First Posted
February 7, 2017
Last Updated
December 20, 2021
Sponsor
Brain and Cognition Discovery Foundation
1. Study Identification
Unique Protocol Identification Number
NCT03053362
Brief Title
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
2. Study Status
Record Verification Date
December 2021
Overall Recruitment Status
Completed
Study Start Date
May 24, 2017 (Actual)
Primary Completion Date
August 8, 2018 (Actual)
Study Completion Date
August 8, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Brain and Cognition Discovery Foundation
4. Oversight
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.
Yes
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Major Depressive Disorder, Cognitive Change
7. Study Design
Primary Purpose
Other
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Determining the effectiveness of a new tool used to detect changes in cognition among individuals with MDD.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
158 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Major Depressive Disorder Population
Arm Type
Experimental
Arm Description
100 Individuals with DSM-5-defined MDD, aged 18-65
All participants receiving vortioxetine for a total of 8 weeks. Participants will receive10 mg/day on days 1-14 of the study treatment period, with the option to increase to vortioxetine 20 mg/day at the end of Week 2 based on physician's judgment. For the remaining 6 weeks, the dose of vortioxetine will be flexible at 10 or 20 mg/day as decided by a research doctor.
Patients will receive the THINC-it over 3 time frame periods. The THINC-it comprised of: Spotter, Symbol Check, Codebreaker, Trails, and PDQ-5-D.
Arm Title
Healthy Control Population
Arm Type
Other
Arm Description
50 Healthy Controls (18-65 years of age) matched on sex, age, and years of education
Intervention Type
Drug
Intervention Name(s)
Vortioxetine
Intervention Description
Observing change in cognition using THINC-it tool in patients with MDD.
Intervention Type
Other
Intervention Name(s)
THINC-it Tool
Intervention Description
Digitalized cognitive test application administering the following cognitive test components:
Digit Symbol Substitution Test (DSST) Choice Reaction Time (CRT) One-back working memory tool Trail Making Test B (TMT-B) Perceived Deficits Questionnaire-5 Depression (PDQ-5-D)
Primary Outcome Measure Information:
Title
Cognition Measured Using the THINC-it Tool
Description
Change in cognition as measured by the objective assessments of cognition within the THINC-it tool. "THINC-it" is the name of the cognition tool and is not an acronym. The objective measurements that comprise the THINC-it tool include the Spotter task (Choice Reaction Time), Symbol Check task(1-back test),Trails task(Trails Making Test B), and Codebreaker task (Digit Symbol Substitution Test). The composite score from all four tests were converted to standard z-score. Higher z-scores indicate better cognition. A z-score of zero indicates population mean.
Time Frame
Baseline and 8 weeks
Secondary Outcome Measure Information:
Title
Changes in Mood as Measured by the Montgomery Åsberg Depression Rating Scale (MADRS)
Description
Changes in mood assessed by the Montgomery Åsberg Depression Rating Scale [MADRS]. The overall score ranges from 0 to 60, where greater scores indicate worse depression.
Time Frame
Baseline and 8 weeks
Title
Changes in Cognitive Function Assessed by the Digit Symbol Substitution Task (DSST)
Description
Changes in cognition assessed by the Digit Symbol Substitution Task (DSST). The outcome measure is the number of correct symbols copied by the participants. Higher scores indicate better performance (minimum score is 0 and maximum is 133).
Time Frame
Baseline and 8 weeks
Title
Changes in Cognitive Function Assessed by the Trail Making Test - Part B (TMT-B)
Description
Changes in cognition assessed by the TMT-B. The outcome measure is time in seconds, where greater time indicates worse performance.
Time Frame
Baseline and 8 weeks
Title
Changes in Global Functional Impairment Using the Sheehan Disability Scale Total Score
Description
Sheehan Disability Scale rates the extent to which his or her 1) work, 2) social life or leisure activities, and 3) home life or family responsibilities are impaired by his or her symptoms on a 10-point visual analog scale. The numerical ratings of 0-10 can be translated into a percentage if desired. The three items may be summed into a single dimensional measure of global functional impairment that ranges from 0 (unimpaired) to 30 (highly impaired).
Time Frame
Baseline and 8 weeks
Title
Changes in the World Health Organization Wellbeing Index (5-Item)
Description
The WHO-5 is a short questionnaire consisting of 5 simple and non-invasive questions, which tap into the subjective well-being of the respondents. The WHO-5 only contains positively phrased items. The respondent is asked to rate how well each of the 5 statements applies to him or her when considering the last 14 days. Each of the 5 items is scored from 5 (all of the time) to 0 (none of the time). The raw score therefore theoretically ranges from 0 (absence of well-being) to 25 (maximal well-being). A percent score out of 25 is reported.
Time Frame
Baseline and 8 weeks
Title
Changes in Changes in Anhedonia From Baseline to Week 8
Description
To establish sensitivity to change in anhedonia using the Snaith-Hamilton Pleasure Scale (SHAPS) total score in adults (18-65) with MDD treated with vortioxetine (10-20 mg flexibly dosed for 8 weeks). Higher score indicates more pleasure, with maximum of 56 points on the scale.
Time Frame
Baseline and 8 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
MDD Population
Inclusion Criteria:
The participant is able and willing to provide informed consent.
The participant is male or female 18-65 years of age.
The participant has received a current diagnosis of a major depressive episode (MDE) as part of MDD as per DSM-5 criteria.
The participant's current MDE is confirmed by the Mini International Neuropsychiatric Interview (M.I.N.I 5.0.).
The participant is an outpatient of a psychiatric setting.
The participant has a MADRS score ≥ 26 at screening and baseline.
The participant's reported duration of the current MDE is at least 3 months.
At least one prior major depressive episode validated by previous treatment (e.g., guideline-informed pharmacotherapy and/or manual-based psychotherapy).
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:
Current alcohol and/or substance use disorder.
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.
Medications approved and/or employed off-label for cognitive dysfunction (e.g., psychostimulants).
Any medication for a general medical disorder that, in the opinion of the investigator, may affect cognitive function (e.g., corticosteroids, beta-blockers).
Use of benzodiazepines within 12 hours of cognitive assessments.
Consumption of alcohol within 8 hours of cognitive assessments.
Recent use of marijuana as determined by a toxicology screen.
Physical, cognitive, or language impairments sufficient to adversely affect data derived from cognitive assessments.
Diagnosis reading disability or dyslexia.
Clinically significant learning disorder by history.
Electroconvulsive therapy (ECT) in the last 6 months.
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.
Pregnant and/or breastfeeding.
Received investigational agents as part of a separate study within 30 days of the screening visit.
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).
Currently receiving treatment with Monoamine Oxidase Inhibitors (MAOIs) anti-depressants, antibiotics such as linezolid, or intravenous methylene blue.
Healthy Control Population
Inclusion Criteria:
No current or past history of mental disorder as evidenced by the M.I.N.I. 5.0 for DSM-IV.
No first-degree relative with an established diagnosis by a healthcare provider of a mood or psychiatric disorder.
No unstable medical disorders.
Exclusion Criteria:
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).
Pregnant and/or breastfeeding.
Consumption of alcohol within 8 hours of THINC-it tool administration.
Recent use of marijuana as determined by a toxicology screen.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Roger McIntyre
Organizational Affiliation
Brain and Cognition Discovery Foundation
Official's Role
Principal Investigator
Facility Information:
Facility Name
CRTCE/KJK Healthplex
City
Toronto
State/Province
Ontario
ZIP/Postal Code
L5C 4E7
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
32670103
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.
Results Reference
derived
PubMed Identifier
31404802
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.
Results Reference
derived
PubMed Identifier
30766492
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.
Results Reference
derived
Learn more about this trial
THINC-it Vortioxetine - Sensitivity to Change
We'll reach out to this number within 24 hrs