Mild Cognitive ImpairmentPhase 2CORT-XNCT04601038
Trial of CORT108297 to Attenuate the Effects of Acute Stress in the Allocortex (CORT-X)
A Phase 2 study testing CORT108297 in people with Mild Cognitive Impairment and Alzheimer Disease, run by Johns Hopkins University at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 55 years and olderHealthy volunteers can take part
- Conditions the study is for
- Mild Cognitive Impairment, Alzheimer Disease, Memory Impairment
- What is being tested?
- CORT108297
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 52 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Jun 2021to 1 Jan 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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;
- Fluent 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.
Who cannot join
- 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;
- 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;
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- 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 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Johns Hopkins School of Medicine
Baltimore, Maryland, 21224
Nick Bienko, MA, 410-550-2036, nbienko1@jhmi.edu
About this study
Official title: Phase II Trial of CORT108297 to Attenuate the Effects of Acute Stress in the Allocortex (CORT-X)
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.
- Being tested
- CORT108297, Placebo
- Keywords
- Stress, Memory loss, Dementia, Alzheimer's disease, Cognitive, Impairment
- Medical subject headings
- Cognitive Dysfunction, Alzheimer Disease, Memory Disorders, Dementia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CORT108297Drug
120mg of a selective glucocorticoid receptor antagonist, taken as 2 tablets daily for 2 weeks
PlaceboDrug
Placebo taken as 2 tablets daily for 2 weeks
| Study group | Role | What they receive |
|---|---|---|
| MCI | Other | Individuals with mild cognitive impairment due to Alzheimer's disease Receives: Drug: CORT108297; Drug: Placebo |
| Cognitively Normal | Other | Individuals who are cognitively normal but who are at risk for Alzheimer's disease Receives: Drug: CORT108297; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Memory 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
Measured: 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)
Measured: 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
Measured: 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)
Measured: After 2 weeks of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Oct 2020
- Study start28 Jun 2021
- Primary completion30 Nov 2027 (estimated)
- Study completion1 Jan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mild Cognitive ImpairmentStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 52 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Collaborators
- Private Philanthropic Funds
- Responsible party
- Sponsor
- Investigators
- Cynthia A Munro, PhD, Principal investigator, Johns Hopkins School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04601038
- Sponsor's protocol ID
- IRB00227116
- Acronym
- CORT-X
- Status last verified
- Jul 2026
- First submitted
- 19 Oct 2020
- Last updated
- 13 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of CORT108297 to Attenuate the Effects of Acute Stress in the Allocortex (CORT-X)
- ClinicalTrials.gov ID
- NCT04601038
- Acronym / sponsor ID
- CORT-X / IRB00227116
- Keywords
- Stress, Memory loss, Dementia, Alzheimer's disease, Cognitive, Impairment
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 52 participants (estimated)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Collaborators
- Private Philanthropic Funds
- Study start
- 28 Jun 2021 (actual)
- Primary completion
- 30 Nov 2027 (estimated)
- Study completion
- 1 Jan 2028 (estimated)
- First posted
- 23 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MCI | Other | Drug: CORT108297, Drug: PlaceboIndividuals with mild cognitive impairment due to Alzheimer's disease |
| Cognitively Normal | Other | Drug: CORT108297, Drug: PlaceboIndividuals who are cognitively normal but who are at risk for Alzheimer's disease |
Who may qualify
- Ages
- 55 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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;
Key exclusion criteria (12 listed)
- 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;
- Bipolar disorder within the past 1 year;
- History of alcohol or drug dependence;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CORT108297120mg of a selective glucocorticoid receptor antagonist, taken as 2 tablets daily for 2 weeks | Drug | Cognitively Normal, MCI |
| PlaceboPlacebo taken as 2 tablets daily for 2 weeks | Drug | Cognitively Normal, MCI |
Primary outcome
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)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jul 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Cynthia A Munro, PhD principal investigator
Johns Hopkins School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing CORT108297 in people with Mild Cognitive Impairment and Alzheimer Disease, run by Johns Hopkins University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 13 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Nicholas Bienko, MS (410-550-2036, nbienko1@jhmi.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Memory as assessed by pattern separation task performance after 2 weeks of treatment with CORT108297 (time frame: After 2 weeks of treatment). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jul 2026.