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

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00476008

Enrollment

Registered

2007-05-21

Start date

2007-07-31

Completion date

2012-10-31

Last updated

2014-08-11

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Alzheimer's Disease

Keywords

Alzheimer's Disease, Mild Alzheimer's Disease, Driving, Driving Impairment

Brief summary

The purpose of the study is to determine whether memantine delays the progression of driving impairment in patients with mild Alzheimer's Disease (AD).

Detailed description

It is well known, and of great concern to both patients and families, that individuals with Alzheimer's disease (AD) eventually become driving impaired. Drivers with dementia are estimated to be 2-8 times more likely to be involved in an automobile crash as unimpaired peers. Approximately half of individuals with mild AD have the skills needed to drive safely. Formal driver evaluation may be necessary to make this distinction. Some reviews in the literature have suggested that individuals identified as high risk, such as those with AD, be advised by their physicians to cease driving altogether. Other studies suggest that these individuals may continue to drive for up to 4 years following diagnosis. Memantine may be effective in delaying the progression of driving impairment in individuals with mild AD. If the investigators can demonstrate a significant delay in the decline in the driving ability, this could extend their driving time and therefore be of immense benefit to patients and their caregivers. Comparison(s): Subjects treated with memantine over a period of 12 months, compared to subjects on placebo.

Interventions

DRUGMemantine

One tablet memantine (Namenda)10mg morning and evening (BID) for 12 months

DRUGPlacebo

One tablet placebo morning and evening (BID) for 12 months

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

60 Years to No maximum

Healthy volunteers

Inclusion criteria

* Men and women ages 60 years of age and older * Subjects must either be previously diagnosed with mild Alzheimer's Disease (AD) by a neurologist, psychiatrist, geriatrician, or be evaluated at a Memory Disorders Center prior to entry into the study * Subjects must have a score of ≥ 23 on the Mini-Mental State Examination (MMSE) at the Screening Visit * Subjects must receive a passing score on the DriveABLE test * Female subjects must be at least 2 years post-menopausal or surgically sterile * Written informed consent must be obtained from the subject prior to the initiation of any study specific procedures

Exclusion criteria

* Subjects who have been treated with a depot neuroleptic within six (6) months of the Screening Visit * Subjects who fail the OPTEC vision test at the screening visit * Subjects who score \> 7 on the Hachinski Test at the screening visit * Subjects with evidence of clinically significant and active pulmonary, gastrointestinal, renal, hepatic, endocrine or cardiovascular system disease (subjects with controlled hypertension, right bundle branch block \[complete or partial\] and pacemakers may be included in the study). Subjects with thyroid disease may also be included in the study, provided they are euthyroid on treatment. Subjects with controlled diabetes may also be included * Recent (\< 2years) B12 or folate deficiency that was considered clinically significant * Subjects with evidence of other psychiatric/neurologic disorders including, but not limited to, stroke, Vascular Dementia, Lewy-Body Disease, Parkinson's Disease, seizure disorder, head injury with loss of consciousness within the past 5 years, any psychotic disorder, or bipolar disorder * Subjects who are taking, or have taken, amantadine, ketamine, dextromethorphan that cannot be discontinued or switched to an allowable alternative medication prior to the minimum allowable interval before Baseline * Subjects who have been in an investigational drug study or who have received treatment with an investigational drug within 30 days (or 5 half-lives, whichever is longer) of the Screening Visit * Any condition, which would make the subject, in the opinion of the investigator, unsuitable for the study * If subjects are taking Acetylcholinesterase inhibitors (AChEls), they must be on a stable dose for \> 3 months prior to baseline. No initiation of AChEls is permitted; discontinuation and dose reduction are permitted

Design outcomes

Primary

Measure	Time frame	Description
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).	Baseline and 12 months	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.

Secondary

Measure	Time frame	Description
Rey Complex Figure Test	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
Trail Making Test - Part A	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.
Trail Making Test - Part B	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.
Mini Mental Status Exam	baseline and 12 months	Scores range from 0-30 with lower scores indicating decreased functioning.
Fuld Object Memory Evaluation	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.
Motor Free Visual Perception Test - Visual Closure Subtest	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.
Cognitive Dementia Rating Scale	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.
Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog)	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.
Useful Field of View	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.

Countries

United States

Participant flow

Recruitment details

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

Pre-assignment details

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.

Participants by arm

Arm	Count
Memantine Memantine : Memantine (Namenda)10mg BID for 12 months	22
Placebo Placebo : Placebo BID for 12 months	21
Total	43

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	4	4
Overall Study	Death	1	0
Overall Study	Physician Decision: Medication Noncompli	2	1
Overall Study	Placebo concerns	2	2
Overall Study	Withdrawal by Subject	0	1

Baseline characteristics

Characteristic	Placebo	Memantine	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	21 Participants	21 Participants	42 Participants
Age, Categorical Between 18 and 65 years	0 Participants	1 Participants	1 Participants
Age, Continuous	80.47 years STANDARD_DEVIATION 5.92	78.13 years STANDARD_DEVIATION 6.38	79.28 years STANDARD_DEVIATION 6.21
Region of Enrollment United States	21 participants	22 participants	43 participants
Sex: Female, Male Female	5 Participants	10 Participants	15 Participants
Sex: Female, Male Male	16 Participants	12 Participants	28 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	6 / 22	9 / 21
serious Total, serious adverse events	2 / 22	3 / 21

Outcome results

Primary

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).

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.

Time frame: 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.

Arm	Measure	Group	Value (NUMBER)	Dispersion
Memantine	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	—
Memantine	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
Placebo	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	9 participants	—
Placebo	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	10 participants	—

Secondary

Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog)

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.