Validation of the THINC-it Tool for Cognitive Dysfunction in Major Depressive Disorder

Study Overview
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Brief Summary
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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. This study is designed to validate a brief user-friendly tool capable of detecting deficit in cognitive performance among adults with MDD. Data will be gathered with the aim to determine whether the proposed tool identifies cognitive deficits in adults with MDD and differentiates the clinical MDD population from healthy controls. 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.

Official Title
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Validation of the THINC-it Tool for Cognitive Dysfunction in Major Depressive Disorder

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Other: THINC-it Tool
* Other: Pencil-and-paper Cognitive Tests


Participation Criteria
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Eligibility Criteria
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MDD Population: Inclusion Criteria: That participant is able and willing to provide informed consent. The participant is male or female between the ages of 18-65. The participant has received a diagnosis of a major depressive disorder (MDE) as per DSM-5 criteria. Current MDE is confirmed by the MINI for DSM-IV-TR. The participant is an outpatient at a psychiatric setting. The participant has a MADRS score equal to or greater than 22. The reported duration of current depressive episode is at least 3 months. The participant has been receiving a stable antidepressant dose for a minimum of 2 weeks prior to the study visit. At least one prior episode by history of depression validated by previous treatment (e.g. guidelines-informed pharmacotherapy and/or manual-based psychotherapy). Health Canada-approved antidepressant; add-on agents commensurate with Canadian (i.e. CANMAT) and American treatment-guidelines for MDD will be permitted. Enrollment in manual-based and/or supportive psychotherapy will be permitted. 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 MINI for DSM-IV-TR. Medications approved for 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 THINC-it tool administration. Consumption of alcohol within 8 hours of THINC-it tool administration. The patient has physical, cognitive, or language impairment of some severity as to adversely affect the validity of the data derived from neuropsychological tests. The patient is diagnosed with a reading disability or dyslexia. The patient cannot have a clinically significant learning disorder by history. The patient has received electroconvulsive therapy (ECT) in the last 6 months. The patient has a history of moderate or severe head trauma (e.g. loss of consciousness for over 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. Healthy Controls: Inclusion Criteria: No current or past history of mental disorder as evidence by MINI or DSM-IV-TR. No first-degree relative with an established diagnosis by a healthcare provider of a mood or psychiatric disorder. No unstable medical disorders. Exclusion Criteria: Any medication for a general medical disorder that in the opinion of the investigator may affect cognitive function (e.g. corticosteroids, beta-blockers). Consumption of alcohol within 8 hours of THINC-it tool administration.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Major Depressive Disorder Population<br>100 Individuals with DSM-5-defined MDD, aged 18-65 | Other: THINC-it Tool<br>* 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)<br>Other: Pencil-and-paper Cognitive Tests<br>* Pencil-and-paper versions of the following cognitive tests: Digit Symbol Substitution Test (DSST) Trail Making Test B (TMT-B) Perceived Deficits Questionnaire-5 Depression (PDQ-5-D) Variant of Choice Reaction Time (CRT) Variant of the One-back working memory tool<br>|
| Healthy Control Population<br>100 healthy controls matched on age, sex and years of education | Other: THINC-it Tool<br>* 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)<br>Other: Pencil-and-paper Cognitive Tests<br>* Pencil-and-paper versions of the following cognitive tests: Digit Symbol Substitution Test (DSST) Trail Making Test B (TMT-B) Perceived Deficits Questionnaire-5 Depression (PDQ-5-D) Variant of Choice Reaction Time (CRT) Variant of the One-back working memory tool<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite THINC-it Tool Score | The composite THINC-it tool score is the integrated total score of results from performance on five sub-component cognitive tests of the THINC-it tool. | up to1 week | 
| Digit Symbol Substitution Test (DSST) - THINC-it tool version |  | Up to 1 week | 
| Choice Reaction Time (CRT) - THINC-it tool version |  | Up to 1 week | 
| One-back working memory test - THINC-it tool version |  | Up to 1 week | 
| Trail Making Test B - THINC-it tool version |  | Up to 1 week | 
| Perceived Deficits Questionnaire 5 item for depression (PDQ-5-D) - THINC-it tool version |  | Up to 1 week | 
| Digit Symbol Substitution Test (DSST) - Pencil-and-paper version |  | Up to 1 week | 
| Choice Reaction Time (CRT) - Pencil-and-paper version |  | Up to 1 week | 
| One-back working memory test - Pencil-and-paper version |  | Up to 1 week | 
| Trail Making Test B - Pencil-and-paper version |  | Up to 1 week | 
| Perceived Deficits Questionnaire 5 item for depression (PDQ-5-D) - Pencil-and paper version |  | Up to 1 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endicott Workplace Productivity Scale (EWPS) |  | Up to 1 week | 
| Sheehan Disability Scale (SDS) |  | Up to 1 week | 
| Pittsburgh Sleep Quality Index (PSQI) |  | Up to 1 week | 
| Clinical Global Impression (CGI) |  | Administered at one timepoint to healthy controls and to subjects with MDD after administration of primary cognitive test instruments. | 
| Montgomery Asberg Depression Rating Scale (MADRS) |  | Up to 1 week | 
| Generalized Anxiety Disorder 7-Item (GAD-7) |  | Administered at one timepoint to healthy controls and to subjects with MDD after administration of primary cognitive test instruments. | 
| WHO-5 Well-being Index (WHO-5) |  | Up to 1 week | 
| Visual Analog Scale (VAS) |  | Up to 1 week |