This will be a two-center, placebo controlled blinded clinical trial to evaluate the safety
and tolerability of efavirenz (EFV) in 36 clinically stable subjects with mild cognitive
impairment/early dementia due to Alzheimer's Disease (AD) age ≥55 years. Of these 36 total
subjects, 18 will be recruited by MGH and 18 will be recruited by UH. A subset of the
subjects at MGH only will also participate in a Stable Isotope Labeling Kinetics (SILK)
protocol with deuterated water (a nonhazardous substance), designed to more precisely measure
EFV effects on CNS cholesterol turnover.
Each respective site's 18 total recruited individuals will be divided into 3 groups: these 3
groups will represent two particular dosages of EFV and a placebo group, respectively. In a
double-blind fashion, participants will be receiving either a capsule of EFV or placebo daily
for 20 weeks. At MGH only, 12 individuals (4 from each of the two EFV groups and placebo)
will participate in the unique "heavy water" SILK protocol assessing the kinetics of
deuterium enrichment in plasma 24-hydroxycholesterol (24-OHC). All study participants at both
sites will have their blood, cerebral spinal fluid, and urine analyzed at various points
throughout the study. All participants will have their DNA genotyped for APOE isoforms (E2,
E3 or E4) and single nucleotide polymorphisms (SNPs) in CYP46A1 (rs754203) and CYP2B6
(rs3745274) to be used for post-hoc analysis.
Phase:
Phase 1
Details
Lead Sponsor:
Case Western Reserve University
Collaborators:
Massachusetts General Hospital University Hospitals Cleveland Medical Center