Trial of CORT108297 to Attenuate the Effects of Acute Stress in the Allocortex (CORT-X) (CORT-X)

July 10, 2026 updated by: Johns Hopkins University

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
52

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Cynthia A Munro, PhD
  • Phone Number: 410-550-6271
  • Email: cmunro@jhmi.edu

Study Contact Backup

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21224
        • Recruiting
        • Johns Hopkins School of Medicine
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

55 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Individuals must meet criteria for mild cognitive impairment due to Alzheimer's disease according to National Institute on Aging (NIA)/Alzheimer's Association recommendations OR be cognitively normal based on clinical and cognitive assessment in the Enrollment Visit and have at least one of the following risk factors for AD:

  • Known to have at least 1 apolipoprotein E (APOE) ε4 allele;
  • Subjective cognitive concerns with a T score < 40 on the Multifactorial Memory Questionnaire Satisfaction Scale;
  • A first-degree relative with dementia.

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;
  • 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.

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;
  • 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 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Other: MCI
Individuals with mild cognitive impairment due to Alzheimer's disease
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
Other: Cognitively Normal
Individuals who are cognitively normal but who are at risk for Alzheimer's disease
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
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
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)
After 2 weeks of treatment
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
After 2 weeks of treatment
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)
After 2 weeks of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Johns Hopkins University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Private Philanthropic Funds

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Cynthia A Munro, PhD, Johns Hopkins School of Medicine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 28, 2021

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 30, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 19, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 19, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 23, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 13, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 10, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IRB00227116

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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