CORT-X will examine if mitigation of stress-mediated pathogenesis of Alzheimer's disease (AD) is a feasible target for intervention in individuals at risk for this disease. This single-site (Baltimore, Maryland) phase II clinical trial is a 2-week, randomized, placebo-controlled crossover study of the effects of the selective glucocorticoid receptor antagonist, CORT108297, on cognitive test performance in 26 individuals with mild cognitive impairment (MCI) due to AD and in 26 cognitively normal individuals with an increased risk for AD due to family history, genetics, and/or subjective memory complaints. All subjects will participate in a brief stressor (public speaking and mental arithmetic) and provide saliva samples so investigators can measure stress hormone response. Then, following 2 weeks of treatment with placebo or CORT108297, in counterbalanced order, participants will complete cognitive tests assessing memory and executive function. All study participants will receive CORT108297 and placebo over the course of this 10-week trial that requires 6 in-person study visits. The primary aims will compare the effects of CORT108297 to placebo on cognitive test performance in individuals with MCI due to AD and in individuals at risk for AD, and describe the side effects of CORT108297 in study participants. Secondary aims will identify subject characteristics that predict positive response to study drug.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
52
120mg of a selective glucocorticoid receptor antagonist, taken as 2 tablets daily for 2 weeks
Placebo taken as 2 tablets daily for 2 weeks
Johns Hopkins School of Medicine
Baltimore, Maryland, United States
RECRUITINGMemory as assessed by pattern separation task performance after 2 weeks of treatment with CORT108297
Percent of correct responses to the "lure" items on the pattern separation task, with 100% indicating a perfect score
Time frame: After 2 weeks of treatment
Memory as assessed by the Hopkins Verbal Learning Test-Revised Edition (HVLT-R) after 2 weeks of treatment with CORT108297
Total number of words recalled in trials 1, 2, 3, and the delayed recall trial of the HVLT-R, with scores ranging from 0 (no words recalled) to 48 (all 12 words recalled after each of the trials)
Time frame: After 2 weeks of treatment
Executive functioning as assessed by the Trail Making Test (TMT), part B after 2 weeks of treatment with CORT108297
Number of seconds required to complete part B of the TMT, with lower scores indicating better performance
Time frame: After 2 weeks of treatment
Executive functioning as assessed by the Digit Span Task (digit span backwards) after 2 weeks of treatment with CORT108297
Total number of correct responses on the backwards trials of the Digit Span Task, with scores ranging from 0 (no trials correct) to 14 (perfect score)
Time frame: After 2 weeks of treatment
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