Remediation of Age-related Cognitive Decline: Vortioxetine and Cognitive Training

Study Overview
=================
Brief Summary
-----------------
The purpose of this research study is to examine the potential benefits of vortioxetine in combination with at-home computerized cognitive training program to improve cognition, such as memory, attention, and concentration. This study will compare the effectiveness of vortioxetine plus cognitive training versus placebo plus cognitive training.

Detailed Description
-----------------
The purpose of this research study is to examine the potential benefits of vortioxetine in combination with at-home computerized cognitive training program to improve cognition, such as memory, attention, and concentration. This study will compare the effectiveness of vortioxetine plus cognitive training versus placebo plus cognitive training. Vortioxetine is considered investigational when used as a treatment for age-related cognitive decline, which means that it has not been approved by the U.S. Food and Drug Administration for this purpose. Vortioxetine is approved by the U.S. Food and Drug Administration as a treatment for depression, and also goes by the name Trintellix (formerly known as Brintellix). That means that, while the drug itself is approved by the FDA, it is not approved for the reasons the investigators are using it in this study. Participation in this study entails an estimated 6 study visits over the course of approximately six months. Participants will complete various assessments at our lab at the Washington University School of Medicine along with check-in visits in-person or over the phone. Additionally, they will participate in at home computerized cognitive training for approximately six months, supplemented with either vortioxetine or placebo. The investigators will assess memory and problem-solving abilities using paper and pencil, computerized measures, and self-assessments of how participants feel. These tests could include numbers, letters, symbols, words, or sentences. These tests will be repeated throughout the study. If eligible to do so, participants will complete a baseline MRI scan. A subset of participants who completed a baseline MRI scan will complete another MRI scan after approximately 26 weeks of vortioxetine or placebo and at home computerized cognitive training.

Official Title
-----------------
Remediation of Age-related Cognitive Decline: Vortioxetine and Cognitive Training

Conditions
-----------------
Age-related Cognitive Decline

Intervention / Treatment
-----------------
* Drug: Vortioxetine 10 mg
* Behavioral: Cognitive training program


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Community-living men and women age 65 and older Age-related cognitive decline as defined by (a) self-reported cognitive dysfunction that is attributed to the aging process (in response to screening questions to the participant); (b) ability to complete cognitive battery, but still scoring less than 1 standard deviation above age-matched norms at both baseline and after the two-week cognitive training lead-in. Exclusion Criteria: Known dementia or other clinical neurodegenerative illness (e.g., Parkinson's disease, cerebrovascular disease) per self-report, informant report, medical records, or neuropsychological testing Any current psychiatric disorder Medical conditions that suggest shortened lifespan, such as metastatic cancer; or would prohibit safe participation in the interventions, including cardiovascular disease or musculoskeletal conditions; or with the assessments. Sensory impairment that would prevent participation IQ < 70 as estimated by the Wechsler Test of Adult Reading Alcohol or substance abuse within 6 months Concurrent cognitive training, such as brain-training software, or other interventions expected to affect neuroplasticity Psychotropic medications or those with likely CNS effects (none within 4 weeks prior to study entry)

Ages Eligible for Study
-----------------
Minimum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vortioxetine plus cognitive training<br>Vortioxetine (10 mg) plus cognitive training 5 times weekly for 30 minutes a day | Drug: Vortioxetine 10 mg<br> <br> * Other names: Trintellix;Behavioral: Cognitive training program<br>* Online training program, 30 minutes a day, 5 times a week<br>|
| Placebo Comparator: Placebo plus cognitive training<br>Placebo plus cognitive training 5 times weekly for 30 minutes a day | Behavioral: Cognitive training program<br>* Online training program, 30 minutes a day, 5 times a week<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Total Fluid Cognitive Score | Total fluid cognitive score from the NIH Toolbox as well as the speed of cognitive improvement The study utilized five cognitive tests from the NIH Toolbox Cognitive Battery that measured fluid cognition-the capacity for new learning and information processing. A higher score indicates indicates better performance on these tests. A total fluid cognitive score at or near 100 indicates ability that is average compared with others nationally. Scores around 115 suggest above-average fluid cognitive ability, while scores around 130 suggest superior ability. Conversely, a score around 85 suggests below-average fluid cognitive ability, and a score in the range of 70 or below suggests significant impairment. | Randomization (0 weeks), 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Total Fluid Cognitive Score | Total fluid cognitive score from the NIH Toolbox as well as the speed of cognitive improvement The study utilized five cognitive tests from the NIH Toolbox Cognitive Battery that measured fluid cognition-the capacity for new learning and information processing. A higher score indicates indicates better performance on these tests. A total fluid cognitive score at or near 100 indicates ability that is average compared with others nationally. Scores around 115 suggest above-average fluid cognitive ability, while scores around 130 suggest superior ability. Conversely, a score around 85 suggests below-average fluid cognitive ability, and a score in the range of 70 or below suggests significant impairment. | Randomization (0 weeks), 4 week, 12 week, 26 week | 
| Participant Function | Participant function assessed using the UCSD Performance-Based Skills Assessment (UPSA). A validated test that required participants to demonstrate their competence to perform everyday functioning tasks in domains such as comprehension, planning, finances, transportation and communication. A higher scores indicates a better outcome. Scores can range from a minimum of 0 to a maximum of 100. | Randomization (0 weeks), 26 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Vortioxetine, Elderly, Online cognitive training