Trial Outcomes & Findings for Delaying the Progression of Driving Impairment in Individuals With Mild Alzheimer's Disease (NCT NCT00476008)

NCT ID: NCT00476008

Last Updated: 2014-08-11

Results Overview

The DriveABLE On-Road Test utilizes a standardized road course and standardized scoring procedures designed to identify driving errors indicative of decline in competence scores. This road test takes approximately 30-45 minutes and covers a distance of approximately 9 miles.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 60 participants
• Primary outcome timeframe: Baseline and 12 months
• Results posted on: 2014-08-11

Participant Flow

Recruitment dates July 2007 - September 2011 Newspaper print ads, physician referral, subject referral, press releases

Prior to randomization, subjects completed a screening visit to discuss/sign informed consent and determine study eligibility. Of the 60 subjects screened, 17 were excluded due to not passing the screening visit driving test, scoring out of the inclusion criteria range on screening visit assessments or meeting an exclusion criteria.

Participant milestones

Measure	Memantine Memantine : Memantine (Namenda)10mg BID for 12 months	Placebo Placebo : Placebo BID for 12 months
Overall Study STARTED	22	21
Overall Study 6 Month Testing	15	14
Overall Study COMPLETED	13	13
Overall Study NOT COMPLETED	9	8

Reasons for withdrawal

Measure	Memantine Memantine : Memantine (Namenda)10mg BID for 12 months	Placebo Placebo : Placebo BID for 12 months
Overall Study Adverse Event	4	4
Overall Study Placebo concerns	2	2
Overall Study Physician Decision: Medication Noncompli	2	1
Overall Study Withdrawal by Subject	0	1
Overall Study Death	1	0

Baseline Characteristics

Delaying the Progression of Driving Impairment in Individuals With Mild Alzheimer's Disease

Baseline characteristics by cohort

Measure	Memantine n=22 Participants Memantine : Memantine (Namenda)10mg BID for 12 months	Placebo n=21 Participants Placebo : Placebo BID for 12 months	Total n=43 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Age, Categorical >=65 years	21 Participants n=5 Participants	21 Participants n=7 Participants	42 Participants n=5 Participants
Age, Continuous	78.13 years STANDARD_DEVIATION 6.38 • n=5 Participants	80.47 years STANDARD_DEVIATION 5.92 • n=7 Participants	79.28 years STANDARD_DEVIATION 6.21 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	5 Participants n=7 Participants	15 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	16 Participants n=7 Participants	28 Participants n=5 Participants
Region of Enrollment United States	22 participants n=5 Participants	21 participants n=7 Participants	43 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 12 months

Population: One subject in the placebo group could not complete the driving test at 12 months due to his vision being below the legal limit to drive.

The DriveABLE On-Road Test utilizes a standardized road course and standardized scoring procedures designed to identify driving errors indicative of decline in competence scores. This road test takes approximately 30-45 minutes and covers a distance of approximately 9 miles.

Outcome measures

Measure	Memantine n=13 Participants Memantine : Memantine (Namenda)10mg BID for 12 months	Placebo n=12 Participants Placebo : Placebo BID for 12 months
The Primary Outcome Measure is the Number of Subjects in Each Group Who Are Able to Pass the DriveABLE On-Road Test at Month 12 (Endpoint). DriveABLE passed	13 participants 0	10 participants
The Primary Outcome Measure is the Number of Subjects in Each Group Who Are Able to Pass the DriveABLE On-Road Test at Month 12 (Endpoint). DriveABLE same or improved	13 participants	9 participants

SECONDARY outcome

Timeframe: baseline and 12 months

Ten common objects in a bag were presented to determine whether the subject could identify objects by touch. The subject was not told that memory of this event would be tested. The subject names each object and then pulls it out of the bag to see if he is correct. After distracting the subject, by asking the patient to say words rapidly from a single category (rapid verbal retrieval), the subject is asked to recall the objects from the bag. The subject was then offered two more chances to learn and recall them (store and retrieve) by reminding the subject of omitted items after each recall, with rapid verbal retrieval preventing rehearsal before each recall opportunity.

Retrieval scores were summed over the three trials with the range of possible scores being 0-30. Lower scores indicate more severe impairment.

Outcome measures

Measure	Memantine n=13 Participants Memantine : Memantine (Namenda)10mg BID for 12 months	Placebo n=13 Participants Placebo : Placebo BID for 12 months
Fuld Object Memory Evaluation Baseline Sum of Retrieval Score	18.87 units on a scale Standard Deviation 5.00	18.38 units on a scale Standard Deviation 8.76
Fuld Object Memory Evaluation 12 month Sum of Retrieval Score	19.08 units on a scale Standard Deviation 8.47	17.94 units on a scale Standard Deviation 5.85

SECONDARY outcome

Timeframe: baseline and 12 months

This is a measure of visual-spatial and constructional ability as well as higher order cognitive processes including planning, organizing, and problem solving. Subjects are asked to copy a complicated drawing. 18 elements are scored from 0-2 depending on accuracy/distortion and location of the reproduction. The maximum score is 36 points. Lower scores indicate more severe impairment

Outcome measures

Measure	Memantine n=13 Participants Memantine : Memantine (Namenda)10mg BID for 12 months	Placebo n=13 Participants Placebo : Placebo BID for 12 months
Rey Complex Figure Test Baseline	27.53 units on a scale Standard Deviation 6.05	29.30 units on a scale Standard Deviation 5.10
Rey Complex Figure Test 12 Months	29.96 units on a scale Standard Deviation 4.54	27.85 units on a scale Standard Deviation 5.75

SECONDARY outcome

Timeframe: baseline and 12 months

A simple test of visual tracking. The score is the time in seconds required to complete. Higher scores indicate lower functioning.

Outcome measures

Measure	Memantine n=13 Participants Memantine : Memantine (Namenda)10mg BID for 12 months	Placebo n=13 Participants Placebo : Placebo BID for 12 months
Trail Making Test - Part A Baseline	50.33 seconds Standard Deviation 17.2	39.63 seconds Standard Deviation 12.37
Trail Making Test - Part A 12 months	53.46 seconds Standard Deviation 22.00	38.54 seconds Standard Deviation 16.32

SECONDARY outcome

Timeframe: baseline and 12 months

This tests cognitive flexibility and set-shifting. It is considered to be a test of executive functioning and has been shown to correlate with on-road driving ability. The score is the time in seconds required to complete each part. Higher scores indicate decreased functioning.

Outcome measures

Measure	Memantine n=13 Participants Memantine : Memantine (Namenda)10mg BID for 12 months	Placebo n=13 Participants Placebo : Placebo BID for 12 months
Trail Making Test - Part B Baseline	195.33 seconds Standard Deviation 128.58	117.75 seconds Standard Deviation 43.03
Trail Making Test - Part B 12 months	233.15 seconds Standard Deviation 159.49	170.92 seconds Standard Deviation 145.33

SECONDARY outcome

Timeframe: baseline and 12 months

Scores range from 0-30 with lower scores indicating decreased functioning.

Outcome measures

Measure	Memantine n=13 Participants Memantine : Memantine (Namenda)10mg BID for 12 months	Placebo n=13 Participants Placebo : Placebo BID for 12 months
Mini Mental Status Exam Baseline	27.67 units on a scale Standard Deviation 1.63	28.13 units on a scale Standard Deviation 2.00
Mini Mental Status Exam 12 Months	26.00 units on a scale Standard Deviation 3.56	27.15 units on a scale Standard Deviation 2.34

SECONDARY outcome

Timeframe: baseline and 12 months

The Useful Field of View is a computer-administered test that measures higher order processing skills such as divided attention and visual processing speed. Scores can be predictive of ability to perform many everyday activities, such as driving a vehicle. Speed of visual processing is measured as the examinee identifies a target, but must also localize a simultaneously presented target displayed in the periphery of the computer monitor. Scores range from 1 to 4 with 1 being no impairment, 2= mild, 3= moderate and 4=serious impairment.

Outcome measures

Measure	Memantine n=13 Participants Memantine : Memantine (Namenda)10mg BID for 12 months	Placebo n=13 Participants Placebo : Placebo BID for 12 months
Useful Field of View Baseline	3.00 units on a scale Standard Deviation 1.31	2.44 units on a scale Standard Deviation 1.50
Useful Field of View 12 months	2.54 units on a scale Standard Deviation 1.45	2.08 units on a scale Standard Deviation 1.38

SECONDARY outcome

Timeframe: baseline and 12 months

This is an 11 item multiple choice test of visual perception. Scores range from 0-11. This test measures visual perception deficits separate from motor skill abilities. Higher scores indicate more severe impairment.

Outcome measures

Measure	Memantine n=13 Participants Memantine : Memantine (Namenda)10mg BID for 12 months	Placebo n=13 Participants Placebo : Placebo BID for 12 months
Motor Free Visual Perception Test - Visual Closure Subtest Baseline	2.93 number incorrect Standard Deviation 2.52	2.00 number incorrect Standard Deviation 2.19
Motor Free Visual Perception Test - Visual Closure Subtest 12 months	3.23 number incorrect Standard Deviation 2.83	2.69 number incorrect Standard Deviation 2.53

SECONDARY outcome

Timeframe: baseline and 12 months

This scale is used to stage severity of dementia. Scores are on a five-point scale in which 0 indicates no cognitive impairment, .5 = very mild dementia,1 = mild, 2 = moderate and 3= severe.

Outcome measures

Measure	Memantine n=13 Participants Memantine : Memantine (Namenda)10mg BID for 12 months	Placebo n=13 Participants Placebo : Placebo BID for 12 months
Cognitive Dementia Rating Scale Baseline	2.30 units on a scale Standard Deviation 1.31	2.41 units on a scale Standard Deviation 1.11
Cognitive Dementia Rating Scale 12 Months	2.31 units on a scale Standard Deviation 2.71	1.81 units on a scale Standard Deviation 1.61

SECONDARY outcome

Timeframe: baseline and 12 months

The ADAS-Cog is a performance based test that measures specific cognitive and behavioral dysfunctions in patients with Alzheimer's disease. The cognitive subscale comprises 11 items which measure word recall (0-10), ability to follow single and multi-step commands (0-5), constructional praxis (0-5), ideational praxis (0-5), naming objects(0-5), word recognition (0-12), orientation (0-8), comprehension of spoken language (0-5), word finding difficulty(0-5) and ability to remember test instructions (0-5). 0 = no impairment with higher scores indicating more severe impairment.

Outcome measures

Measure	Memantine n=13 Participants Memantine : Memantine (Namenda)10mg BID for 12 months	Placebo n=13 Participants Placebo : Placebo BID for 12 months
Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) 1) Word Recall - Baseline	4.33 units on a scale Standard Deviation 1.28	4.00 units on a scale Standard Deviation 1.26
Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) 1) Word Recall - 12 Months	4.56 units on a scale Standard Deviation 1.97	4.13 units on a scale Standard Deviation 1.31
Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) 2) Commands - Baseline	.40 units on a scale Standard Deviation .51	0 units on a scale Standard Deviation 0
Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) 3) Constructional Praxis - Baseline	3.40 units on a scale Standard Deviation .51	3.44 units on a scale Standard Deviation .63
Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) 4) Ideational Praxis - Baseline	5.00 units on a scale Standard Deviation 0	5.00 units on a scale Standard Deviation 0
Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) 4) Ideational Praxis - 12 months	4.92 units on a scale Standard Deviation .28	5.00 units on a scale Standard Deviation 0
Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) 5) Naming - Baseline	1.80 units on a scale Standard Deviation 1.70	2.38 units on a scale Standard Deviation 3.93
Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) 5) Naming - 12 months	1.31 units on a scale Standard Deviation 1.38	1.77 units on a scale Standard Deviation 1.69
Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) 6) Orientation - Baseline	.80 units on a scale Standard Deviation 1.01	.44 units on a scale Standard Deviation 1.09
Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) 6) Orientation - 12 Months	.85 units on a scale Standard Deviation 1.34	.46 units on a scale Standard Deviation .88
Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) 7) Word Recognition - Baseline	9.60 units on a scale Standard Deviation 6.07	7.27 units on a scale Standard Deviation 5.42
Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) 7) Word Recognition - 12 Months	8.10 units on a scale Standard Deviation 8.39	9.31 units on a scale Standard Deviation 4.91
Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) 8) Remember Test Instructions - Baseline	0.00 units on a scale Standard Deviation 0	0.00 units on a scale Standard Deviation 0
Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) 8) Remember Test Instructions - 12 Months	0.00 units on a scale Standard Deviation 0	0.00 units on a scale Standard Deviation 0
Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) 9) Spoken Language - Baseline	.20 units on a scale Standard Deviation .77	0.00 units on a scale Standard Deviation 0
Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) 9) Spoken Language - 12 Months	.23 units on a scale Standard Deviation .83	0 units on a scale Standard Deviation 1.00
Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) 10) Word Finding - Baseline	.13 units on a scale Standard Deviation .52	0.00 units on a scale Standard Deviation 0
Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) 10) Word Finding - 12 Months	.15 units on a scale Standard Deviation .55	.08 units on a scale Standard Deviation .28
Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) 11) Comprehension - Baseline	.07 units on a scale Standard Deviation .26	.06 units on a scale Standard Deviation .25
Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) 11) Comprehension - 12 Months	.31 units on a scale Standard Deviation .63	.15 units on a scale Standard Deviation .38
Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) 2) Commands - 12 Months	.23 units on a scale Standard Deviation .60	.85 units on a scale Standard Deviation 2.76
Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) 3) Constructional Praxis - 12 Months	3.54 units on a scale Standard Deviation .52	3.46 units on a scale Standard Deviation .52

Adverse Events

Memantine

Serious events: 2 serious events

Other events: 6 other events

Deaths: 0 deaths

Placebo

Serious events: 3 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Measure	Memantine n=22 participants at risk Memantine : Memantine (Namenda)10mg BID for 12 months	Placebo n=21 participants at risk Placebo : Placebo BID for 12 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Mouth Cancer	4.5% 1/22 • Number of events 1	0.00% 0/21
Cardiac disorders Myocardial Infarction	4.5% 1/22 • Number of events 1	0.00% 0/21
General disorders Generalized Weakness	0.00% 0/22	4.8% 1/21 • Number of events 1
Vascular disorders Stroke	0.00% 0/22	4.8% 1/21 • Number of events 1
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal carcinoma	0.00% 0/22	4.8% 1/21 • Number of events 1

Other adverse events

Measure	Memantine n=22 participants at risk Memantine : Memantine (Namenda)10mg BID for 12 months	Placebo n=21 participants at risk Placebo : Placebo BID for 12 months
General disorders Dizziness	9.1% 2/22 • Number of events 2	0.00% 0/21
General disorders Fatigue	18.2% 4/22 • Number of events 4	14.3% 3/21 • Number of events 3
Nervous system disorders Headache	9.1% 2/22 • Number of events 2	0.00% 0/21
Gastrointestinal disorders Decreased Appetite	9.1% 2/22 • Number of events 2	0.00% 0/21
Nervous system disorders Insomnia	9.1% 2/22 • Number of events 2	0.00% 0/21
Psychiatric disorders Depression	0.00% 0/22	9.5% 2/21 • Number of events 2
Gastrointestinal disorders Nausea	0.00% 0/22	14.3% 3/21 • Number of events 3
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal Cell Carcinoma	0.00% 0/22	9.5% 2/21 • Number of events 2
Gastrointestinal disorders Constipation	0.00% 0/22	14.3% 3/21 • Number of events 3
Endocrine disorders Hypothyroidism	0.00% 0/22	9.5% 2/21 • Number of events 2
Respiratory, thoracic and mediastinal disorders Pneumonia	0.00% 0/22	9.5% 2/21 • Number of events 2

Additional Information

Peter Holland, MD

Charles E. Schmidt College of Medicine, Florida Atlantic University

Phone: 561-297-0164

Email: holland@fau.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place