The Cognitive Effects of Lorazepam in Healthy Older Individuals With TOMM40 Variable-length Polymorphisms

• ClinicalTrials.gov Identifier: NCT01780519
• Recruitment Status: Completed
• First Posted: January 31, 2013
• Last Update Posted: November 10, 2016
• Sponsor: Mayo Clinic
• Information provided by (Responsible Party): Cynthia M. Stonnington, M.D., Mayo Clinic

Tracking Information

• First Submitted Date: January 29, 2013
• First Posted Date: January 31, 2013
• Last Update Posted Date: November 10, 2016
• Study Start Date: January 2013
• Actual Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 27, 2016)

Groton Maze Learning Test (GMLT) score [ Time Frame: baseline to 5 hours ]

The GMLT assesses visuospatial working memory, error monitoring, information processing speed, and short-term delayed recall for a complex hidden maze. Subjects are familiarized with the task during two untimed practice tests, and once the tester is confident that the subject understands the rules and can move easily around the grid, the timed test is administered. In each of the 5 successive trials of the GMLT exam, the subject is asked to learn to navigate his or her way around a 28-step maze that is hidden beneath a 10 x 10 grid of squares on the computer touch screen. For each trial, the time to completion, number of correct moves, number of wrong moves, and the number of perseverative errors are recorded.

Original Primary Outcome Measures (submitted: January 30, 2013)

• AVLT Long term memory score [ Time Frame: baseline to 5 hours ]
  The AVLT (Rey Auditory Verbal Learning Test), a verbal memory test, is a 15-word list presented over 5 learning trials. After each presentation, the subject immediately repeats as many words as possible, then does so again after 30 minutes, which is the "long-term memory" score. "Percent recall" is long-term memory divided by learning trial 5. The "learning over trials" score reflects the increment in words repeated over the 5 successive learning trials. Six equivalent alternate forms of the AVLT will be randomly assigned to each subject.
• Groton Maze Learning Test (GMLT) score [ Time Frame: baseline to 5 hours ]
  The GMLT assesses visuospatial working memory, error monitoring, information processing speed, and short-term delayed recall for a complex hidden maze. Subjects are familiarized with the task during two untimed practice tests, and once the tester is confident that the subject understands the rules and can move easily around the grid, the timed test is administered. In each of the 5 successive trials of the GMLT exam, the subject is asked to learn to navigate his or her way around a 28-step maze that is hidden beneath a 10 x 10 grid of squares on the computer touch screen. For each trial, the time to completion, number of correct moves, number of wrong moves, and the number of perseverative errors are recorded.

Current Secondary Outcome Measures (submitted: September 27, 2016)

• Auditory Verbal Learning Test (AVLT) Long-term memory score [ Time Frame: baseline to 5 hours ]
  The AVLT assesses verbal memory
• Two Back Test (TBK) [ Time Frame: baseline to 5 hours ]
  The TBK measures working memory

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: The Cognitive Effects of Lorazepam in Healthy Older Individuals With TOMM40 Variable-length Polymorphisms
• Official Title: The Cognitive Effects of Lorazepam in Healthy Older Individuals With TOMM40 Variable-length Polymorphisms
• Brief Summary: The investigators' goal is to determine if certain tests of memory and attention, performed while sleepiness is induced by a single dose of lorazepam, can predict whether or not an individual is at risk for developing Alzheimer's disease.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Basic Science
• Condition: Alzheimer's Disease (AD)

Intervention

Drug: lorazepam

single dose of 1 mg lorazepam

Other Name: Ativan

Study Arms

• L/VL APOE e3/e4 carrier
  long and very long poly - T variants of TOMM40 and APOE e3/e4 carrier
  Intervention: Drug: lorazepam
• L/S APOE e3/e4 carrier
  long and short poly - T variants of TOMM40 and APOE e3/e4 carrier
  Intervention: Drug: lorazepam
• S/VL APOE e3/e3 carrier
  short and Very long poly - T variants of TOMM40 and APOE e3/e3 carrier
  Intervention: Drug: lorazepam
• VL/VL APOE e3/e3 carrier
  Very long poly - T variants of TOMM40 and APOE e3/e3 carrier
  Intervention: Drug: lorazepam
• S/S APOE e3/e3 carrier
  short poly - T variants of TOMM40 and APOE e3/e3 carrier
  Intervention: Drug: lorazepam

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 28, 2016): 57
• Original Estimated Enrollment (submitted: January 30, 2013): 75
• Actual Study Completion Date: September 2016
• Actual Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion criteria:

• Mini-Mental State Examination (MMSE) score of 28-30
• Hamilton Depression Rating Scale score of less than 10
• participants in longitudinal study of aging and have a TOMM40 genotype of S/S, VL/VL, S/VL, L/S or L/VL.

Exclusion criteria:

• Alzheimer's Disease or Mild Cognitive Impairment
• any significant medical, psychiatric, and neurological illnesses, e.g., impaired liver or kidney function, prior stroke, traumatic brain injury, memory impairment, cognitive impairment, parkinsonism, a lifetime history of schizophrenia, bipolar disorder, a psychoactive substance use disorder, or current major depression.
• known allergy to benzodiazepines
• current use (within the previous four weeks) of benzodiazepines or other medications known to interact with lorazepam, current use of sedating antihistamines, or current use of stimulant medications

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 50 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01780519
• Other Study ID Numbers: 12-006469
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Cynthia M. Stonnington, M.D., Mayo Clinic
• Original Responsible Party: Same as current
• Current Study Sponsor: Mayo Clinic
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Cynthia Stonnington, MD; Mayo Clinic

• PRS Account: Mayo Clinic
• Verification Date: November 2016