Testing a drug to reduce stress effects on memory in Alzheimer's patients

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

This study is testing if a new drug can help reduce the negative effects of stress on memory for people at risk of Alzheimer's disease.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 52 (estimated)
• Ages: 55 Years and up
• Sex: All
• Sponsor: Johns Hopkins University (Academic / other)
• Locations: 1 site (Baltimore, Maryland)
• Trial ID: NCT04601038 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates whether the selective glucocorticoid receptor antagonist, CORT108297, can mitigate stress-related cognitive decline in individuals at risk for Alzheimer's disease. It is a two-week, randomized, placebo-controlled crossover study involving 52 participants, including those with mild cognitive impairment and cognitively normal individuals with risk factors for Alzheimer's. Participants will undergo a brief stressor and provide saliva samples to measure stress hormone responses, followed by cognitive testing after treatment. The study aims to assess the drug's impact on memory and executive function.

Who should consider this trial

Good fit: Ideal candidates include individuals aged 55 and older with mild cognitive impairment due to Alzheimer's or cognitively normal individuals with specific risk factors for Alzheimer's.

Not a fit: Patients who are not at risk for Alzheimer's disease or do not meet the eligibility criteria will likely not benefit from this study.

Why it matters

Potential benefit: If successful, this intervention could improve cognitive function and quality of life for individuals at risk of Alzheimer's disease.

How similar studies have performed: Other studies have explored stress management in cognitive decline, but this specific approach using CORT108297 is novel.

Eligibility criteria

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;
* 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 this trial is running

Baltimore, Maryland

• Johns Hopkins School of Medicine — Baltimore, Maryland, United States (Recruiting)

Study contacts

• Principal investigator: Cynthia A Munro, PhD — Johns Hopkins School of Medicine
• Study coordinator: Nicholas Bienko, MS

Conditions Mild Cognitive Impairment; Alzheimer Disease; Memory Impairment; Stress; Memory loss; Dementia; Alzheimer's disease; Cognitive