Evaluation of DCTclock™ as a Cognitive Assessment Aid

• Sponsor: Digital Cognition Technologies (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03238001
• Collaborator: (none)
• Enrollment: 450
• Location: 1
• Arm: 1
• Actual Duration (Months): 4.4
• Patients Per Site Per Month: 103

Study Details

Study Description

Brief Summary

The overall objective of this study is to demonstrate the safety and effectiveness of DCTclock as an adjunctive tool for use by clinicians to evaluate cognitive function in adults aged 55-95.

Condition or Disease	Intervention/Treatment	Phase
Cognitive Function	Device: DCTclock	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 450 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: This study uses a paired design in which each subject undergoes blinded testing by separate testers administering DCTclock and a battery of reference standard tests to determine cognitive state.This study uses a paired design in which each subject undergoes blinded testing by separate testers administering DCTclock and a battery of reference standard tests to determine cognitive state.
• Masking: None (Open Label)
• Primary Purpose: Screening
• Official Title: Evaluation of DCTclock™ as a Cognitive Assessment Aid
• Actual Study Start Date: Jul 11, 2017
• Actual Primary Completion Date: Nov 21, 2017
• Actual Study Completion Date: Nov 21, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: All qualified participants Participants received DCTclock, Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and a battery of other traditional pen and paper neuropsychological assessments.	Device: DCTclock; DCTclock is a quick and non-invasive test that measures cognitive function based on a computerized algorithmic analysis of the entire drawing process and output of a well-established cognitive assessment called The Clock Drawing Test (CDT).

Outcome Measures

Primary Outcome Measures

1. Non-Inferiority of DCTclock Compared to Mini-Mental State Examination (MMSE) [Visit 1 (day 1)]

   The primary analysis will assess agreement between DCTclock and the Montreal Cognitive Assessment (MoCA) and compare it to the agreement between the MMSE and MoCA at visit 1.

Secondary Outcome Measures

1. Quadratic Weighted Kappa on Primary Endpoints [Visit 1 (day 1)]

   Quadratic weighted Cohen's kappa with 95% CI between DCTclock and MoCA, as well as between MMSE and MoCA.

2. Percent Agreement on Primary Endpoints [Visit 1 (day 1)]

   Positive percent agreement, version A (treating the "Indeterminate" group as "Unimpaired") and version B (removing the "Indeterminate" group from the analysis), and negative percent agreement version A and version B. These were calculated for the DCTclock/MoCA classification table as well as the MMSE/MoCA classification table. 95% CI were also calculated and compared between the two classification tables' calculations.

3. Regression Coefficients on Primary Endpoints [Visit 1 (day 1)]

   Linear and rank-linear regression coefficients (slope, intercept) and 95% CI for DCTclock regressed on MoCA as well as for the MMSE regressed on MoCA.

4. Correlation Coefficients on Primary Endpoints [Visit 1 (day 1)]

   Pearson and Spearman correlation coefficients between DCTclock and MoCA as well as between MMSE and MoCA.

5. Quadratic Weighted Kappa on Secondary Endpoints (Test-Retest Reliability) [Visit 1 and visit 2, occurring 1-4 weeks apart]

   Quadratic weighted Cohen's Kappa statistics were calculated for both DCTclock and MMSE test-retest data (visit 1 vs visit 2).

6. Percent Agreement on Secondary Endpoints (Test-retest Reliability) [Visit 1 and visit 2, occurring 1-4 weeks apart]

   Positive percent agreement version A (treating the "Indeterminate" group as "Unimpaired") and version B (removing the "Indeterminate" group from the analysis), negative percent agreement version A and version B, indeterminate percent agreement, and unimpaired percent agreement.

7. Regression Coefficients on Secondary Endpoints (Test-retest Reliability) [Visit 1 and visit 2, occurring 1-4 weeks apart]

   Deming, linear, and rank-linear correlation coefficients (intercept, slope) were calculated for visit 1 regressed on visit 2 for both DCTclock and MMSE.

8. Correlation Coefficients on Secondary Endpoints (Test-retest Reliability) [Visit 1 and visit 2, occurring 1-4 weeks apart]

   Pearson and Spearman correlation coefficients were calculated between visit 1 and visit 2 for DCTclock and MMSE, along with 95% CI.

Other Outcome Measures

1. Construct Validity of DCTclock as Measured by the Comparison of DCTclock Results to the Results of a Battery of Neuropsychological Assessments [Visit 1 (day 1)]

   The goal of this analysis is to assess the construct validity of DCTclock. Specifically, the goal is to compare scores from the administration of DCTclock to the visit 1 administration of a battery of neuropsychological tests, to characterize the psychometric properties of DCTclock, and to compare those properties to the properties of MMSE.

2. Incidence of Serious Device-related Adverse Events [Safety] [Visit 1 and visit 2, occuring 1-4 weeks apart]

   Incidence of serious device-related adverse events.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 55 Years to 95 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Men and women 55 to 95 years old.

Exclusion Criteria:

• Ineligible for written informed consent.

• Physical impairment of the writing hand.

• Impaired manual dexterity.

• Impaired vision.

• Under the influence of recreational drugs or alcohol at the time of the visit.

• Current or recent participation in a clinical trial that includes the use of a drug or intervention to alter cognitive function.

• Recent cognitive testing.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Compass Research	Maitland	Florida	United States	32751

Sponsors and Collaborators

• Digital Cognition Technologies

Investigators

• Study Director: Antonia H Holway, Ph.D., Digital Cognition Technologies, Inc.

Study Documents (Full-Text)

• Statistical Analysis Plan - Dec 19, 2017
• Study Protocol - Jan 3, 2018

More Information

Publications

• Cohen J, Penney DL, Davis R, Libon DJ, Swenson RA, Ajilore O, Kumar A, Lamar M. Digital Clock Drawing: differentiating "thinking" versus "doing" in younger and older adults with depression. J Int Neuropsychol Soc. 2014 Oct;20(9):920-8. doi: 10.1017/S1355617714000757. Epub 2014 Sep 15.
• Davis R, Libon DJ, Au R, Pitman D, Penney DL. THink: Inferring Cognitive Status from Subtle Behaviors. Proc Conf AAAI Artif Intell. 2014 Jul;2014:2898-2905.
• Lamar M, Ajilore O, Leow A, Charlton R, Cohen J, GadElkarim J, Yang S, Zhang A, Davis R, Penney D, Libon DJ, Kumar A. Cognitive and connectome properties detectable through individual differences in graphomotor organization. Neuropsychologia. 2016 May;85:301-9. doi: 10.1016/j.neuropsychologia.2016.03.034. Epub 2016 Mar 30.
• Souillard-Mandar W, Davis R, Rudin C, Au R, Libon DJ, Swenson R, Price CC, Lamar M, Penney DL. Learning Classification Models of Cognitive Conditions from Subtle Behaviors in the Digital Clock Drawing Test. Mach Learn. 2016 Mar;102(3):393-441. Epub 2015 Oct 20.

• Responsible Party: Digital Cognition Technologies
• ClinicalTrials.gov Identifier: NCT03238001
• Other Study ID Numbers: DCT032
• First Posted: Aug 3, 2017
• Last Update Posted: Apr 3, 2018
• Last Verified: Mar 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Digital Cognition Technologies: Cognitive assessment; Cognition; Clock Test

Study Results

Participant Flow

Recruitment Details	Participants were enrolled at one site in the US.
Pre-assignment Detail	450 participants were enrolled. 14 did not meet screening criteria.

Arm/Group Title	All Qualified Participants
Arm/Group Description	Participants received the DCTclock test and a battery of other traditional, pen and paper, neuropsychological assessments.
Period Title: Visit 1 (Primary Endpoint Cohort)
STARTED	436
COMPLETED	432
NOT COMPLETED	4
Period Title: Visit 1 (Primary Endpoint Cohort)
STARTED	432
COMPLETED	403
NOT COMPLETED	29

Baseline Characteristics

Arm/Group Title	All Participants
Arm/Group Description	All participants enrolled in the study.
Overall Participants	450
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	68.94 (8.78)
Sex/Gender, Customized (Count of Participants)
Male	114 25.3%
Female	333 74%
Unknown or Other	3 0.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	38 8.4%
Not Hispanic or Latino	405 90%
Unknown or Not Reported	7 1.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	6 1.3%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	105 23.3%
White	329 73.1%
More than one race	4 0.9%
Unknown or Not Reported	6 1.3%
Handedness (Count of Participants)
Right handed	396 88%
Left handed	34 7.6%
Ambidextrous	13 2.9%
Other or unknown	7 1.6%
Highest education level attained (Count of Participants)
College Degree +	148 32.9%
High School and some college	141 31.3%
High school	106 23.6%
Less than high school	45 10%
Unknown	10 2.2%

Outcome Measures

1. Primary Outcome

Title	Non-Inferiority of DCTclock Compared to Mini-Mental State Examination (MMSE)
Description	The primary analysis will assess agreement between DCTclock and the Montreal Cognitive Assessment (MoCA) and compare it to the agreement between the MMSE and MoCA at visit 1.
Time Frame	Visit 1 (day 1)

Outcome Measure Data

Analysis Population Description

The Evaluable Population includes all qualified participants undergoing cognitive testing with DCTclock, MMSE, and MoCA who completed visit 1.

Arm/Group Title	Primary Endpoint (Evaluable) Population
Arm/Group Description	Participants received DCTclock, MMSE, MoCA, and a battery of other traditional pen and paper neuropsychological assessments.
Measure Participants	432
Number (90% Confidence Interval) [Difference in Quadratic Weighted Kappas]	-0.035

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Primary Endpoint (Evaluable) Population
	Comments	A two-one-sided tests approach was taken, where, prior to analysis, it was determined that a delta (equivalence margin) of 0.20 would be considered a significant difference between the DCTclock/MoCA kappa and the MMSE/MoCA kappa. The reasoning behind this determination can be found in the study's statistical analysis plan.
	Type of Statistical Test	Non-Inferiority
	Comments	In order to show non-inferiority, a lower 90% confidence limit (CL) for the difference in kappa scores would need to be greater than or equal to -0.20. The 90% confidence interval was calculated based on 5000 bootstrapped differences in kappa scores.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Lower 90% CL for difference in Kappas
	Estimated Value	-0.12
	Confidence Interval	(2-Sided) 90%; -0.12 to 0.05
	Parameter Dispersion	Type: Value:
	Estimation Comments	90% CI for Kappa of DCTclock/MoCA - Kappa of MMSE/MoCA (estimated with bootstrap method using 5000 bootstraps).

2. Secondary Outcome

Title	Quadratic Weighted Kappa on Primary Endpoints
Description	Quadratic weighted Cohen's kappa with 95% CI between DCTclock and MoCA, as well as between MMSE and MoCA.
Time Frame	Visit 1 (day 1)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	DCTclock	MMSE
Arm/Group Description	Participants received DCTclock and MoCA on their first visit.	Participants received MMSE and MoCA on their first visit.
Measure Participants	432	432
Number (95% Confidence Interval) [Quadratic Weighted Kappa]	0.40	0.44

3. Secondary Outcome

Title	Percent Agreement on Primary Endpoints
Description	Positive percent agreement, version A (treating the "Indeterminate" group as "Unimpaired") and version B (removing the "Indeterminate" group from the analysis), and negative percent agreement version A and version B. These were calculated for the DCTclock/MoCA classification table as well as the MMSE/MoCA classification table. 95% CI were also calculated and compared between the two classification tables' calculations.
Time Frame	Visit 1 (day 1)

Outcome Measure Data

Analysis Population Description

Version A treats the "Indeterminate" group as "Unimpaired", while version B removes the "Indeterminate" group from the analysis. Thus, the analysis population for version B is smaller than the overall analysis population.

Arm/Group Title	DCTclock	MMSE
Arm/Group Description	Participants received DCTclock and MoCA on their first visit.	Participants received MMSE and MoCA on their first visit.
Measure Participants	432	432
Positive - Version A	0.64	0.56
Positive - Version B	0.78	0.69
Negative - Version A	0.74	0.83
Negative - Version B	0.73	0.88

4. Secondary Outcome

Title	Regression Coefficients on Primary Endpoints
Description	Linear and rank-linear regression coefficients (slope, intercept) and 95% CI for DCTclock regressed on MoCA as well as for the MMSE regressed on MoCA.
Time Frame	Visit 1 (day 1)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	DCTclock	MMSE
Arm/Group Description	Participants received DCTclock and MoCA on their first visit.	Participants received MMSE and MoCA on their first visit.
Measure Participants	432	432
Linear - Intercept	19.35	-5.03
Linear - Slope	0.07	1.03
Rank-Linear - Intercept	107.75	96.45
Rank-Linear - Slope	0.50	0.55

5. Secondary Outcome

Title	Correlation Coefficients on Primary Endpoints
Description	Pearson and Spearman correlation coefficients between DCTclock and MoCA as well as between MMSE and MoCA.
Time Frame	Visit 1 (day 1)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	DCTclock	MMSE
Arm/Group Description	Participants received DCTclock and MoCA on their first visit	Participants received MMSE and MoCA on their first visit.
Measure Participants	432	432
Pearson	0.53	0.59
Spearman	0.50	0.55

6. Secondary Outcome

Title	Quadratic Weighted Kappa on Secondary Endpoints (Test-Retest Reliability)
Description	Quadratic weighted Cohen's Kappa statistics were calculated for both DCTclock and MMSE test-retest data (visit 1 vs visit 2).
Time Frame	Visit 1 and visit 2, occurring 1-4 weeks apart

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	DCTclock	MMSE
Arm/Group Description	Participants received DCTclock on their first and second visits, occurring 1-4 weeks apart.	Participants received MMSE on their first and second visits, occurring 1-4 weeks apart.
Measure Participants	403	403
Number (95% Confidence Interval) [Quadratic Weighted Cohen's Kappa]	0.53	0.48

7. Secondary Outcome

Title	Percent Agreement on Secondary Endpoints (Test-retest Reliability)
Description	Positive percent agreement version A (treating the "Indeterminate" group as "Unimpaired") and version B (removing the "Indeterminate" group from the analysis), negative percent agreement version A and version B, indeterminate percent agreement, and unimpaired percent agreement.
Time Frame	Visit 1 and visit 2, occurring 1-4 weeks apart

Outcome Measure Data

Analysis Population Description

Version A treats the "Indeterminate" group as "Unimpaired", while version B removes the "Indeterminate" group from the analysis. Thus, the analysis population for version B is smaller than the overall analysis population.

Arm/Group Title	DCTclock	MMSE
Arm/Group Description	Participants received DCTclock on their first and second visits, occurring 1-4 weeks apart.	Participants received MMSE on their first and second visits, occurring 1-4 weeks apart.
Measure Participants	403	403
Positive - Version A	0.73	0.74
Positive - Version B	0.85	0.84
Negative - Version A	0.76	0.80
Negative - Version B	0.81	0.78
Indeterminate	0.21	0.27
Unimpaired	0.61	0.63

8. Secondary Outcome

Title	Regression Coefficients on Secondary Endpoints (Test-retest Reliability)
Description	Deming, linear, and rank-linear correlation coefficients (intercept, slope) were calculated for visit 1 regressed on visit 2 for both DCTclock and MMSE.
Time Frame	Visit 1 and visit 2, occurring 1-4 weeks apart

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	DCTclock	MMSE
Arm/Group Description	Participants received DCTclock on their first and second visits, occurring 1-4 weeks apart.	Participants received MMSE on their first and second visits, occurring 1-4 weeks apart.
Measure Participants	403	403
Deming - Intercept	8.77	2.96
Deming - Slope	0.93	0.91
Linear - Intercept	25.03	10.88
Linear - Slope	0.66	0.62
Rank-Linear - Intercept	66.48	91.16
Rank-Linear - Slope	0.67	0.55

9. Secondary Outcome

Title	Correlation Coefficients on Secondary Endpoints (Test-retest Reliability)
Description	Pearson and Spearman correlation coefficients were calculated between visit 1 and visit 2 for DCTclock and MMSE, along with 95% CI.
Time Frame	Visit 1 and visit 2, occurring 1-4 weeks apart

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	DCTclock	MMSE
Arm/Group Description	Participants received DCTclock on their first and second visits, occurring 1-4 weeks apart.	Participants received MMSE on their first and second visits, occurring 1-4 weeks apart.
Measure Participants	403	403
Pearson	0.70	0.67
Spearman	0.67	0.56

10. Other Pre-specified Outcome

Title	Construct Validity of DCTclock as Measured by the Comparison of DCTclock Results to the Results of a Battery of Neuropsychological Assessments
Description	The goal of this analysis is to assess the construct validity of DCTclock. Specifically, the goal is to compare scores from the administration of DCTclock to the visit 1 administration of a battery of neuropsychological tests, to characterize the psychometric properties of DCTclock, and to compare those properties to the properties of MMSE.
Time Frame	Visit 1 (day 1)

Outcome Measure Data

Analysis Population Description

Includes all qualified participants who completed testing at visit 1 and had evaluable data for each test analyzed. Roughly half of the population was administered the full neuropsychological battery. The remainder completed a partial battery (see protocol for details).

Arm/Group Title	DCTclock	MMSE
Arm/Group Description	Participants received DCTclock, MMSE, MoCA, and a battery of other traditional pen and paper neuropsychological assessments.	Participants received DCTclock, MMSE, MoCA, and a battery of other traditional pen and paper neuropsychological assessments.
Measure Participants	432	432
MMSE	0.50	NA
MoCA	0.53	0.59
Benton Judgment of Line Orientation	0.34	0.36
Delis-Kaplan Executive Function- Letter Fluency	0.36	0.34
Delis-Kaplan Executive Function-Category Fluency	0.39	0.37
Delis-Kaplan Executive Function-Category Switching	0.30	0.38
Delis-Kaplan Executive Function- Switch Accuracy	0.26	0.36
Rey-Osterrieth Complex Figure- Copy	0.44	0.43
Rey-Osterrieth Complex Figure- Immediate	0.43	0.31
Rey-Osterrieth Complex Figure- Delayed	0.39	0.28
Rey-Osterrieth Complex Figure- Immediate Retention	0.22	0.08
Rey-Osterrieth Complex Figure- Delayed Retention	-0.06	0.03
Rey-Osterrieth Complex Figure- Organization	0.29	0.25
WAIS-IV Digit Span	0.32	0.48
WAIS-IV Block Design	0.39	0.42
Trail Making Part A	0.48	0.45
Trail Making Part B	0.49	0.51
Geriatric Depression Scale	-0.11	-0.04
Symbol Digit Modalities	0.51	0.49
Hamilton-Veale Contrast Sensitivity - Left	0.12	0.10
Hamilton-Veale Contrast Sensitivity- Right	0.09	0.17
Hamilton-Veale Contrast Sensitivity- Binocular	0.24	0.21
Purdue Peg Board- Left hand	0.32	0.16
Purdue Peg Board- Right hand	0.35	0.22
Purdue Peg Board- Bimanual	0.36	0.25

11. Other Pre-specified Outcome

Title	Incidence of Serious Device-related Adverse Events [Safety]
Description	Incidence of serious device-related adverse events.
Time Frame	Visit 1 and visit 2, occuring 1-4 weeks apart

Outcome Measure Data

Analysis Population Description

All qualified participants who completed at least one DCTclock test.

Arm/Group Title	All Participants
Arm/Group Description	Participants received DCTclock, MMSE, MoCA, and a battery of other traditional pen and paper neuropsychological assessments.
Measure Participants	432
Count of Participants [Participants]	0 0%

Adverse Events

Time Frame	Adverse event data was collected at each study visit. The second (final) study visit occurred one to four weeks after the first visit, therefore, adverse event data was collected for a period of one to four weeks.
Arm/Group Title	All Participants
Arm/Group Description	Participants received DCTclock, MMSE, MoCA, and a battery of other traditional, pen and paper neuropsychological assessments.
All Cause Mortality
	All Participants
	Affected / at Risk (%)	# Events
Total	0/436 (0%)
Serious Adverse Events
	All Participants
	Affected / at Risk (%)	# Events
Total	1/436 (0.2%)
Injury, poisoning and procedural complications
Bone fracture	1/436 (0.2%)	1
Other (Not Including Serious) Adverse Events
	All Participants
	Affected / at Risk (%)	# Events
Total	0/436 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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