Hydrocortisone for Memory Impairment
Trial Summary
What is the purpose of this trial?
Chronic corticosteroid (CS) exposure is associated with changes in memory and the hippocampus in both humans and in animal models. The hippocampus has a high concentration of glucocorticoid receptors (GCRs), and the pre-clinical literature demonstrates shortening of apical dendrites in the CA3 region of the hippocampus and decreased neurogenesis in the dentate gyrus (DG) following CS administration. In humans, both stress and CS exposure are associated with a decline in declarative memory performance (a process mediated by the hippocampus). Impairment in declarative memory and hippocampal atrophy are reported in patients with excessive CS release due to Cushing's disease, and, by our group, in patients receiving prescription CS therapy. These findings have important implications for patients with mood disorders, as a large subset of people with major depressive disorder (MDD) show evidence of HPA axis activation, elevated cortisol and, importantly, resistance to the effects of CSs on both the HPA axis and on declarative memory. Thus, resistance to corticosteroids appears to be a consequence of MDD. this study will examine changes in declarative memory, as well as use state-of-the-art high-resolution multimodal neuroimaging, including structural and functional (i.e., task-based and resting state) MRI, in both men and women healthy controls, and, as an exploratory aim, a depressed group, given 3-day exposures to hydrocortisone (160 mg/day) or placebo. The study will translate preclinical findings to humans, provide valuable data on possible sex differences in the response to cortisol and, for the first time, identify specific hippocampal subfields (e.g., CA3/DG) in humans that are most sensitive to acute CS effects. Using resting state fMRI data and whole brain connectomics using graph theoretical approaches, we will determine the effects of cortisol exposure on functional brain networks. Furthermore, this will be the first study to use neuroimaging to compare the brain's response to CSs in people with depression vs. controls, and determine whether depressed people demonstrate glucocorticoid resistance within the hippocampus. We hypothesize that hippocampal response to acute CSs will be greatest in the CA3/DG subfield, greater in women than in men, and that depressed people will show a blunted hippocampal response to CSs compared to controls. A multidisciplinary research team with extensive experience in CS effects on the brain and hippocampal subfield neuroimaging, and a prior history of research collaboration, will conduct the project.
Will I have to stop taking my current medications?
Yes, participants must stop taking any CNS-acting medications (like antidepressants or antipsychotics) as the depressed group needs to be medication-free.
What evidence supports the effectiveness of the drug hydrocortisone for memory impairment?
Research shows that low-dose hydrocortisone can enhance learning and memory in certain groups, like HIV-infected men, and young adults have shown improved working memory with hydrocortisone. However, studies in the elderly have not found significant memory improvements, suggesting age-related differences in response.12345
How does the drug hydrocortisone differ from other treatments for memory impairment?
Hydrocortisone is unique because it is a synthetic form of cortisol, a hormone that can affect memory and cognitive function. While elevated cortisol levels are often linked to memory issues, this trial explores hydrocortisone's potential effects on memory impairment, which is not a standard treatment approach for this condition.45678
Research Team
Sherwood Brown, MD, PhD
Principal Investigator
University of Texas Southwestern Medical Center
Eligibility Criteria
This trial is for men and women aged 18-40 with normal to slightly overweight BMI, at least a high school education, and normal memory function. Healthy participants must have minimal depressive symptoms, while the depressed group should have moderate but not severe depression. Participants need good vision (correctable) for MRI tasks.Inclusion Criteria
Exclusion Criteria
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
Treatment
Participants receive either hydrocortisone or placebo for 3 days, followed by a 25-day washout period, then crossover to the alternate treatment for another 3 days
Neuroimaging and Testing
High-resolution multimodal neuroimaging and neurocognitive testing are conducted to assess hippocampal subfield volume and activation
Follow-up
Participants are monitored for safety and effectiveness after treatment
Treatment Details
Interventions
- Hydrocortisone (Corticosteroid)
- Placebo Oral Tablet (Other)
Hydrocortisone is already approved in Canada for the following indications:
- Adrenal insufficiency
- Allergic reactions
- Asthma
- Severe acute pancreatitis
Find a Clinic Near You
Who Is Running the Clinical Trial?
University of Texas Southwestern Medical Center
Lead Sponsor
University of California, Irvine
Collaborator
National Institute of Mental Health (NIMH)
Collaborator