- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03896659
Exploring the Effects of Corticosteroids on the Human Hippocampus
Exploring the Effects of Corticosteroids on the Human Hippocampus Using Neurocognitive Testing and High Resolution Neuroimaging
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.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Estimated)
Phase
- Phase 4
Contacts and Locations
Study Contact
- Name: Sherwood Brown
- Phone Number: 2146456950
- Email: sherwood.brown@utsouthwestern.edu
Study Contact Backup
- Name: Shuchi Lakhanpal
- Phone Number: 214-645-6954
- Email: Shuchi.Lakhanpal@UTSouthwestern.edu
Study Locations
-
-
Texas
-
Dallas, Texas, United States, 75390
- Recruiting
- UT Southwestern Medical Center
-
Contact:
- Traci Holmes
- Phone Number: 214-645-6959
- Email: traci.holmes@utsouthwestern.edu
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Men and women age 18-50 years with vision corrected to at least 20-40 (needed for fMRI tasks)
- Education of ≥ 12 years
- Baseline RAVLT total words recalled T-score ≥ 40 (normal range)
- BMI between 18.5-35.0 (neither underweight nor severely obese)
- Baseline QIDS-C ≤ 5 (virtual absence of depressive symptoms) for "healthy controls" and for the "depressed" group a QIDS-C between 11-20 (≥ moderate depressive symptoms but < very severe depressive symptoms)
Exclusion Criteria:
- History of major psychiatric illness other than MDD for the depressed group, defined as bipolar disorder, posttraumatic stress disorder, schizoaffective disorder, schizophrenia, eating disorders, or MDD with psychotic features. For the control group, a past episode of MDD (per SCID) is also exclusionary
- History of drug or alcohol use disorder
- History of neurological disorders including seizures, brain surgery, multiple sclerosis, Parkinson's disease
- Taking CNS-acting medications (e.g., antidepressants, antipsychotics, lithium, anticonvulsants, sedative/hypnotic/anxiolytics). Thus, the depressed group will be medication free.
- History of allergic reaction or medical contraindication to hydrocortisone
- Metal implants, claustrophobia, or other contraindications to MRI
- Significant medical conditions (e.g., cancer, heart disease, diabetes)
- Vulnerable population including pregnant or nursing women, prisoners, and people with intellectual disability, history of special education classes, dementia, or other severe cognitive disorders
- Current suicidal ideation, a suicide attempt in the past 12 months or more than one lifetime attempt
- History of systemic CS use in the past 12 months, lifetime cumulative use of more than 12 weeks, or recent (defined as past 28 days) inhaled CS use
- Women who are using estrogen containing oral contraceptive agents (other contraceptives are acceptable, see Protection of Human Subjects section for a list of acceptable birth control methods) or who are post- or peri-menopausal or with irregular menstrual cycles (i.e., inconsistent menstruation patterns)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Depressed: Hydrocortisone, then Placebo
Participants in the "depressed' arm will receive a Hydrocortisone 160 mg tablet every day for 3 days.
After a washout period of 25 days, they then will receive a Placebo tablet (matching Hydrocortisone 160 mg tablet) every day for 3 days.
|
Hydrocortisone 160 mg tablet
Hydrocortisone-matched Placebo tablet
|
Experimental: Depressed: Placebo, then Hydrocortisone
Participants in the "depressed' arm will receive a Placebo tablet (matching Hydrocortisone 160 mg tablet) every day for 3 days.
After a washout period of 25 days, they then will receive a Hydrocortisone 160 mg tablet every day for 3 days.
|
Hydrocortisone 160 mg tablet
Hydrocortisone-matched Placebo tablet
|
Experimental: Healthy Controls: Hydrocortisone, then Placebo
Participants in the "healthy control" arm will receive a Hydrocortisone 160 mg tablet every day for 3 days.
After a washout period of 25 days, they then will receive a Placebo tablet (matching Hydrocortisone 160 mg tablet) every day for 3 days.
|
Hydrocortisone 160 mg tablet
Hydrocortisone-matched Placebo tablet
|
Experimental: Healthy Controls: Placebo, then Hydrocortisone
Participants in the "healthy control" arm will receive a Placebo tablet (matching Hydrocortisone 160 mg tablet) every day for 3 days.
After a washout period of 25 days, they then will receive a Hydrocortisone 160 mg tablet every day for 3 days.
|
Hydrocortisone 160 mg tablet
Hydrocortisone-matched Placebo tablet
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Hippocampal subfield activation
Time Frame: 3 days
|
Task-based hippocampal activation during functional neuroimaging.
|
3 days
|
Hippocampal subfield volume
Time Frame: 3 days
|
High resolution structural neuroimaging will be used to generate regional hippocampal subfield volume.
|
3 days
|
Collaborators and Investigators
Investigators
- Principal Investigator: Sherwood Brown, MD, PhD, University of Texas Southwestern Medical Center
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- STU-2018-0360
- 1R01MH115932-01A1 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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.
Clinical Trials on Depression
-
ProgenaBiomeRecruitingDepression | Depression, Postpartum | Depression, Anxiety | Depression Moderate | Depression Severe | Clinical Depression | Depression in Remission | Depression, Endogenous | Depression ChronicUnited States
-
Washington University School of MedicineCompletedTreatment Resistant Depression | Late Life Depression | Geriatric Depression | Refractory Depression | Therapy-Resistant DepressionUnited States, Canada
-
University of California, San FranciscoRecruitingDepression Moderate | Depression Mild | Depression, TeenUnited States
-
University GhentUniversiteit Antwerpen; Janssen-Cilag Ltd.RecruitingDepression Moderate | Depression Severe | Depression MildBelgium
-
Baylor College of MedicineUniversity of TexasRecruitingDepression | Depression Moderate | Depression Severe | Suicide and Self-harm | Depression in Adolescence | Depression MildUnited States
-
University of Cape TownNational Institute of Mental Health (NIMH)CompletedPostpartum Depression | Clinical Depression | Moderate DepressionSouth Africa
-
Washington University School of MedicinePatient-Centered Outcomes Research Institute; National Institute of Mental...CompletedMajor Depressive Disorder | Treatment Resistant Depression | Treatment-Refractory Depression | Late Life Depression | Geriatric DepressionUnited States, Canada
-
Northern Illinois UniversityUniversity Autonoma de Santo DomingoTerminatedDepression Moderate | Depression MildUnited States, Dominican Republic
-
Gerbera Therapeutics, Inc.Not yet recruitingPostpartum Depression | Depression, Postpartum | Postnatal Depression | Post-partum Depression | Post-Natal DepressionUnited States
-
Lawson Health Research InstituteTerminated
Clinical Trials on Hydrocortisone Oral
-
ShireCompletedAdrenal Insufficiency
-
Johns Hopkins UniversityNational Institute of Mental Health (NIMH)Completed
-
Sansum Diabetes Research InstituteWithdrawnType 1 DiabetesUnited States
-
Assistance Publique - Hôpitaux de ParisCompletedBronchopulmonary DysplasiaFrance
-
Horus UniversityRecruitingSubacromial Impingement Syndrome | Impingement SyndromeEgypt
-
University Hospital Southampton NHS Foundation...Imperial College London; University of Bristol; University Hospitals Bristol... and other collaboratorsCompleted
-
Charite University, Berlin, GermanyCompletedPlacebo | Hydrocortisone | Yohimbine | Yohimbine + HydrocortisoneGermany
-
Ulla Feldt-RasmussenUnknown
-
University of VersaillesAssistance Publique - Hôpitaux de ParisTerminatedPneumonia, Viral | Influenza in HumansFrance
-
Central Institute of Mental Health, MannheimGerman Research FoundationCompletedPosttraumatic Stress DisorderGermany