NCT04601038 · Johns Hopkins University
Trial of CORT108297 to Attenuate the Effects of Acute Stress in the Allocortex (CORT-X)
(CORT-X)
What this study is about
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.
View original scientific description
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.
Interventions
DRUG
CORT108297
120mg of a selective glucocorticoid receptor antagonist, taken as 2 tablets daily for 2 weeks
DRUG
Placebo
Placebo taken as 2 tablets daily for 2 weeks
Primary outcome measures
Memory as assessed by pattern separation task performance after 2 weeks of treatment with CORT108297
Time frame: After 2 weeks of treatment
Percent of correct responses to the "lure" items on the pattern separation task, with 100% indicating a perfect score
Memory as assessed by the Hopkins Verbal Learning Test-Revised Edition (HVLT-R) after 2 weeks of treatment with CORT108297
Time frame: After 2 weeks of treatment
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)
Executive functioning as assessed by the Trail Making Test (TMT), part B after 2 weeks of treatment with CORT108297
Time frame: After 2 weeks of treatment
Number of seconds required to complete part B of the TMT, with lower scores indicating better performance
Executive functioning as assessed by the Digit Span Task (digit span backwards) after 2 weeks of treatment with CORT108297
Time frame: After 2 weeks of treatment
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)
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- for all subjects:
- At least 55 years of age;
- Body mass index \>17 and \<30;
- Post-menopausal (if female)
- Non-smoker;
- Availability of a study partner who has frequent contact with the subject (10+ hours/week in person and by telephone), and is able to provide an independent evaluation of functioning;
- Native English speaker;
- Good general health with no disease expected to interfere with the study;
- Willing and able to participate for the duration of the study.
Exclusion criteria
- for all subjects:
- Participation in a therapeutic clinical trial at any time during the study;
- Abnormal corrected QT interval using Bazett's formula (QTcB; defined as \> 450 ms for men and \> 470 ms for women) as determined on ECG;
- Any significant neurologic disease other than suspected incipient Alzheimer's disease, such as Parkinson's disease, multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic deficits or known structural brain abnormalities, including lacunes in critical memory structures including the hippocampus and parahippocampal cortex;
- Major depression, bipolar disorder within the past 1 year;
- History of alcohol or drug dependence;
- Any significant systemic illness or unstable medical condition, which could lead to difficulty complying with the protocol;
- General surgery within the last 3 months;
- Sensory impairment (poor vision or hearing) significant enough to interfere with ability to provide valid cognitive test data;
- Treatment within the last six months with antidepressants, neuroleptics, sedative hypnotics, or glucocorticoids;
- Treatment within the last six months with medications metabolized by the CYP2C9 or CYP2C19 enzymes, most notably clopidogrel and proton pump inhibitors;
- Concurrent use of a CYP3A inhibitor, including grapefruit juice, and St. John's Wort;
- Exceptions to these guidelines may be considered on a case-by-case basis at the discretion of the PI.
Where
- Baltimore, Maryland
Collaborators
Private Philanthropic Funds
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Jul 13, 2026 · Source of record for eligibility and locations