The Impact of Lorazepam on Cognition in APOE e4 Carriers

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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.

Condition or disease	Intervention/treatment	Phase
Alzheimer's Disease	Drug: lorazepam; Drug: placebo	Not Applicable

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.

Study Design

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	36 participants
Allocation:	Randomized
Intervention Model:	Crossover Assignment
Masking:	Triple (Participant, Care Provider, Investigator)
Primary Purpose:	Screening
Official Title:	The Impact of Lorazepam on Cognition in APOE e4 Carriers
Study Start Date :	December 2005
Actual Primary Completion Date :	July 2007
Actual Study Completion Date :	July 2007

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
Active Comparator: 1; single 2 mg dose of lorazepam	Drug: lorazepam; single 2 mg dose of lorazepam; Other Name: Ativan
Placebo Comparator: 2; single dose of placebo	Drug: placebo; single dose of placebo

Outcome Measures

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. Groton Maze Learning Task [ Time Frame: baseline, 2.5 hours and 5 hours ]

Secondary Outcome Measures :

1. Auditory Verbal Learning Test [ Time Frame: baseline, 2.5 hours and 5 hours ]
2. 1-back test [ Time Frame: baseline, 2.5 hours and 5 hours ]

Eligibility Criteria

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	50 Years to 65 Years (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes

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

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

United States, Arizona
Mayo Clinic
Scottsdale, Arizona, United States, 85259

Sponsors and Collaborators

Mayo Clinic

National Institute of Mental Health (NIMH)

Investigators

Principal Investigator:	Cynthia M Stonnington, M.D.	Mayo Clinic

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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

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.

Responsible Party:	Cynthia Stonnington, M.D., Mayo Clinic
ClinicalTrials.gov Identifier:	NCT00586430 History of Changes
Other Study ID Numbers:	929-05
First Posted:	January 4, 2008
Last Update Posted:	January 4, 2008
Last Verified:	December 2007

Keywords provided by Mayo Clinic:

apolipoprotein E e4; Alzheimer's disease; somnolence; Early detection

Additional relevant MeSH terms:

Alzheimer Disease; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Lorazepam; Anticonvulsants; Antiemetics; Autonomic Agents	Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Hypnotics and Sedatives; Central Nervous System Depressants; Anti-Anxiety Agents; Tranquilizing Agents; Psychotropic Drugs; GABA Modulators; GABA Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action