Remediation of Age-related Cognitive Decline: Vortioxetine and Cognitive Training (BBS)

• ClinicalTrials.gov Identifier: NCT03272711
• Recruitment Status: Completed
• First Posted: September 5, 2017
• Results First Posted: January 14, 2020
• Last Update Posted: January 14, 2020
• Sponsor: Washington University School of Medicine
• Collaborators: Queen's University; Takeda
• Information provided by (Responsible Party): Washington University School of Medicine

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Age-related Cognitive Decline
• Interventions: Drug: Vortioxetine 10 mg; Behavioral: Cognitive training program
• Enrollment: 129

Participant Flow

Recruitment Details
Pre-assignment Details	Twenty-nine participants were not assigned to a group. Twenty did not meet eligibility criteria for randomization, 8 individuals declined to participate further and one person was a pilot participant.

Arm/Group Title	Vortioxetine Plus Cognitive Training	Placebo Plus Cognitive Training
Arm/Group Description	Vortioxetine (10 mg) plus cognitive training 5 times weekly for 30 minutes a day Vortioxetine 10 mg Cognitive training program: Online training program, 30 minutes a day, 5 times a week	Placebo plus cognitive training 5 times weekly for 30 minutes a day Cognitive training program: Online training program, 30 minutes a day, 5 times a week
Period Title: Overall Study
Started	51	49
Completed	44	41
Not Completed	7	8

Baseline Characteristics

Arm/Group Title		Vortioxetine Plus Cognitive Training	Placebo Plus Cognitive Training	Total
Arm/Group Description		Vortioxetine (10 mg) plus cognitive training 5 times weekly for 30 minutes a day Vortioxetine 10 mg Cognitive training program: Online training program, 30 minutes a day, 5 times a week	Placebo plus cognitive training 5 times weekly for 30 minutes a day Cognitive training program: Online training program, 30 minutes a day, 5 times a week	Total of all reporting groups
Overall Number of Baseline Participants		51	49	100
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	51 participants	49 participants	100 participants
		71.68 (4.77)	71.88 (5.3)	71.78 (5.01)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	51 participants	49 participants	100 participants
	Female	28 54.9%	23 46.9%	51 51.0%
	Male	23 45.1%	26 53.1%	49 49.0%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	51 participants	49 participants	100 participants
	Hispanic or Latino	1 2.0%	1 2.0%	2 2.0%
	Not Hispanic or Latino	50 98.0%	48 98.0%	98 98.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	51 participants	49 participants	100 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	1 2.0%	1 1.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	9 17.6%	9 18.4%	18 18.0%
	White	40 78.4%	38 77.6%	78 78.0%
	More than one race	2 3.9%	1 2.0%	3 3.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	51 participants	49 participants	100 participants
		51	49	100
Years of Schooling; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	51 participants	49 participants	100 participants
		16.80 (2.48)	16.63 (3.24)	16.72 (2.87)

Outcome Measures

1. Primary Outcome

Title	Change in Total Fluid Cognitive Score
Description	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.
Time Frame	Randomization (0 weeks), 4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vortioxetine Plus Cognitive Training	Placebo Plus Cognitive Training
Arm/Group Description:	Vortioxetine (10 mg) plus cognitive training 5 times weekly for 30 minutes a day Vortioxetine 10 mg Cognitive training program: Online training program, 30 minutes a day, 5 times a week	Placebo plus cognitive training 5 times weekly for 30 minutes a day Cognitive training program: Online training program, 30 minutes a day, 5 times a week
Overall Number of Participants Analyzed	51	49
Mean (Standard Deviation); Unit of Measure: score on a scale
Change in Total Fluid Cognitive Score	6.14 (7.80)	3.71 (7.27)
Week 4 Total Fluid Cogntive Score	106.06 (17.06)	105.85 (12.38)

2. Secondary Outcome

Title	Change in Total Fluid Cognitive Score
Description	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.
Time Frame	Randomization (0 weeks), 4 week, 12 week, 26 week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vortioxetine Plus Cognitive Training	Placebo Plus Cognitive Training
Arm/Group Description:	Vortioxetine (10 mg) plus cognitive training 5 times weekly for 30 minutes a day Vortioxetine 10 mg Cognitive training program: Online training program, 30 minutes a day, 5 times a week	Placebo plus cognitive training 5 times weekly for 30 minutes a day Cognitive training program: Online training program, 30 minutes a day, 5 times a week
Overall Number of Participants Analyzed	51	49
Mean (Standard Deviation); Unit of Measure: score on a scale
Change at Week 4	6.14 (7.8)	3.71 (7.27)
Change at Week 12	8.24 (7.82)	3.93 (6.70)
Change at Week 26	7.55 (7.95)	6.05 (8.26)
Total Fluid Cognitive Score at Week 4	106.06 (17.06)	105.85 (12.38)
Total Fluid Cognitive Score at Week 12	108.12 (16.34)	105.57 (12.31)
Total Fluid Cognitive Score at Week 26	106.98 (17.19)	107.51 (11.44)

3. Secondary Outcome

Title	Participant Function
Description	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.
Time Frame	Randomization (0 weeks), 26 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vortioxetine Plus Cognitive Training	Placebo Plus Cognitive Training
Arm/Group Description:	Vortioxetine (10 mg) plus cognitive training 5 times weekly for 30 minutes a day Vortioxetine 10 mg Cognitive training program: Online training program, 30 minutes a day, 5 times a week	Placebo plus cognitive training 5 times weekly for 30 minutes a day Cognitive training program: Online training program, 30 minutes a day, 5 times a week
Overall Number of Participants Analyzed	51	49
Mean (Standard Deviation); Unit of Measure: score on a scale
Change in UPSA Score	2.91 (7.26)	1.66 (8.73)
Total UPSA Score at Week 26	84.50 (8.80)	82.44 (8.59)

Adverse Events

Time Frame	26 weeks
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Vortioxetine Plus Cognitive Training		Placebo Plus Cognitive Training
Arm/Group Description	Vortioxetine (10 mg) plus cognitive training 5 times weekly for 30 minutes a day Vortioxetine 10 mg Cognitive training program: Online training program, 30 minutes a day, 5 times a week		Placebo plus cognitive training 5 times weekly for 30 minutes a day Cognitive training program: Online training program, 30 minutes a day, 5 times a week
All-Cause Mortality
	Vortioxetine Plus Cognitive Training		Placebo Plus Cognitive Training
	Affected / at Risk (%)		Affected / at Risk (%)
Total	0/51 (0.00%)		0/49 (0.00%)
Serious Adverse Events
	Vortioxetine Plus Cognitive Training		Placebo Plus Cognitive Training
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/51 (0.00%)		2/49 (4.08%)
Cardiac disorders
Worsening of Coronary Artery Disease † [1]	0/51 (0.00%)	0	1/49 (2.04%)	1
Infections and infestations
Hospitalization for Bacterial Infection †	0/51 (0.00%)	0	1/49 (2.04%)	1
† Indicates events were collected by systematic assessment; [1] Hospitalization post bypass surgery
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	1%
	Vortioxetine Plus Cognitive Training		Placebo Plus Cognitive Training
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	31/51 (60.78%)		21/49 (42.86%)
Gastrointestinal disorders
nausea †	15/51 (29.41%)		2/49 (4.08%)
Constipation †	4/51 (7.84%)		1/49 (2.04%)
Diarrhea †	3/51 (5.88%)		3/49 (6.12%)
Vomiting †	2/51 (3.92%)		0/49 (0.00%)
General disorders
viral illness †	9/51 (17.65%)		8/49 (16.33%)
Dizziness †	3/51 (5.88%)		0/49 (0.00%)
Musculoskeletal aches †	3/51 (5.88%)		3/49 (6.12%)
Dental infectkons/aches †	3/51 (5.88%)		1/49 (2.04%)
Skin and subcutaneous tissue disorders
Rashes or pruritis †	5/51 (9.80%)		3/49 (6.12%)
† Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Dr. Eric Lenze
• Organization: Washington University School of Medicine
• Phone: 314-362-1671
• EMail: lenzee@wustl.edu

Publications:

Ball K, Berch DB, Helmers KF, Jobe JB, Leveck MD, Marsiske M, Morris JN, Rebok GW, Smith DM, Tennstedt SL, Unverzagt FW, Willis SL; Advanced Cognitive Training for Independent and Vital Elderly Study Group. Effects of cognitive training interventions with older adults: a randomized controlled trial. JAMA. 2002 Nov 13;288(18):2271-81. doi: 10.1001/jama.288.18.2271.

Bowie CR, Gupta M, Holshausen K, Jokic R, Best M, Milev R. Cognitive remediation for treatment-resistant depression: effects on cognition and functioning and the role of online homework. J Nerv Ment Dis. 2013 Aug;201(8):680-5. doi: 10.1097/NMD.0b013e31829c5030.

Kozauer N, Katz R. Regulatory innovation and drug development for early-stage Alzheimer's disease. N Engl J Med. 2013 Mar 28;368(13):1169-71. doi: 10.1056/NEJMp1302513. Epub 2013 Mar 13. No abstract available.

Lampit A, Hallock H, Valenzuela M. Computerized cognitive training in cognitively healthy older adults: a systematic review and meta-analysis of effect modifiers. PLoS Med. 2014 Nov 18;11(11):e1001756. doi: 10.1371/journal.pmed.1001756. eCollection 2014 Nov.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Lenze EJ, Stevens A, Waring JD, Pham VT, Haddad R, Shimony J, Miller JP, Bowie CR. Augmenting Computerized Cognitive Training With Vortioxetine for Age-Related Cognitive Decline: A Randomized Controlled Trial. Am J Psychiatry. 2020 Jun 1;177(6):548-555. doi: 10.1176/appi.ajp.2019.19050561. Epub 2020 Mar 26. Erratum In: Am J Psychiatry. 2020 Jun 1;177(6):556.

• Responsible Party: Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT03272711
• Other Study ID Numbers: 201509107
• First Submitted: September 1, 2017
• First Posted: September 5, 2017
• Results First Submitted: December 2, 2019
• Results First Posted: January 14, 2020
• Last Update Posted: January 14, 2020