Clinical trial NCT00586430: The Impact of Lorazepam on Cognition in APOE e4 Carriers
Official title: The Impact of Lorazepam on Cognition in APOE e4 Carriers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Alzheimer's Disease
Keywords: apolipoprotein E e4
Alzheimer's disease
somnolence
Early detection
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2008-01-04
Enrollment: 36
Sex: ALL
Minimum age (years): 50
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: SCREENING

Brief summary: We expect the results of this pilot study to justify a larger study that follows people to determine if certain tests of memory and attention, performed while sleepiness is induced by a single dose of lorazepam (a widely used anti-anxiety medication) could predict an individual's risk of developing AD. We plan to compare cognitively normal people who possess a common gene that increases risk for AD- the apolipoprotein E (APOE) e4 allele-to individuals without this gene. We hypothesize that a single 2 mg dose of lorazepam will cause more cognitive impairment in carriers of the APOE e4 allele than in noncarriers, and that the carriers will recover more slowly from these impairments than noncarriers.

Detailed description: We aim to compare measures of memory and information processing speed at 2.5 hours and 5 hours after the administration of a 2 mg dose of lorazepam or placebo in cognitively normal, 50-65 year old APOE e4 carriers and noncarriers, and determine the differential impact of lorazepam on cognition at each time point. Twenty carriers and 20 noncarriers matched for age, sex, and education will be drawn from a database of persons who have already undergone genotyping for an ongoing study at the Mayo Clinic, excluding people with evidence of depression or cognitive impairment and other medical, neurological or psychiatric conditions. Using a double blind, crossover design, subjects will receive either placebo or a 2 mg dose of lorazepam after baseline testing. Equivalent tests will be repeated 2.5 and 5 hours post challenge. The data analysis will compare APOE e4 carriers to noncarriers.

Eligibility criteria: Inclusion Criteria:

* a score of at least 28 on the MMSE
* a score of less than 10 points on the HAM-D-17
* age 50-65
* genotype APOE e3/e4 or APOE e4 non-carriers
* cognitively normal

Exclusion Criteria:

* significant medical, psychiatric, or neurological illnesses
* use of benzodiazepines within the previous four weeks
* currently using sedating antihistamines

Primary outcomes:
measure: Groton Maze Learning Task
timeFrame: baseline, 2.5 hours and 5 hours
Secondary outcomes:
measure: Auditory Verbal Learning Test
timeFrame: baseline, 2.5 hours and 5 hours
measure: 1-back test
timeFrame: baseline, 2.5 hours and 5 hours
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic
state: Arizona
Study officials:
affiliation: Mayo Clinic
name: Cynthia M Stonnington, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Stonnington CM, Snyder PJ, Hentz JG, Reiman EM, Caselli RJ. Double-blind crossover study of the cognitive effects of lorazepam in healthy apolipoprotein E (APOE)-epsilon4 carriers. J Clin Psychiatry. 2009 Oct;70(10):1379-84. doi: 10.4088/JCP.08m04593. Epub 2009 Jun 30.