HydrocortisonePhase 4NCT03896659
Exploring the Effects of Corticosteroids on the Human Hippocampus
A Phase 4 study testing Hydrocortisone Oral in people with Hydrocortisone and Depression, run by University of Texas Southwestern Medical Center at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Hydrocortisone, Depression, Healthy Volunteers
- What is being tested?
- Hydrocortisone Oral
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 66 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2019to 16 Sep 2024
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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)
Who cannot join
- 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
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- 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)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
- Conditions
- Hydrocortisone, Depression, Healthy Volunteers
- Being tested
- Hydrocortisone Oral, Placebo Oral Tablet
- Medical subject headings
- Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hydrocortisone OralDrug
Hydrocortisone 160 mg tablet
Placebo Oral TabletDrug
Hydrocortisone-matched Placebo tablet
| Study group | Role | What they receive |
|---|---|---|
| Depressed: Hydrocortisone, then Placebo | Experimental | 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. Receives: Drug: Hydrocortisone Oral; Drug: Placebo Oral Tablet |
| Depressed: Placebo, then Hydrocortisone | Experimental | 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. Receives: Drug: Hydrocortisone Oral; Drug: Placebo Oral Tablet |
| Healthy Controls: Hydrocortisone, then Placebo | Experimental | 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. Receives: Drug: Hydrocortisone Oral; Drug: Placebo Oral Tablet |
| Healthy Controls: Placebo, then Hydrocortisone | Experimental | 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. Receives: Drug: Hydrocortisone Oral; Drug: Placebo Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hippocampal Subfield Activation (Left Hemisphere)
The z-scores of hippocampal subregions and hemispheres represent the standardized difference in activation between correct and incorrect conditions of the mnemonic discrimination task, where a Z-score of 0 represents the mean difference across all voxels, and each unit reflects one standard deviation from that mean. To compare brain activation between conditions, separate beta weights were estimated for correct and incorrect trials across all trials. These beta weights represent the voxel-wise blood oxygen level (BOLD)-dependent signal, reflecting changes in neural activity associated with each condition. Positive z-scores indicate greater activation for correct relative to incorrect trials, whereas negative z-scores indicate greater activation for incorrect relative to correct trials. Larger absolute z-scores indicate stronger condition-related effects; there are no established clinical thresholds for these experimental activation differences.
Measured: 3 days
Hippocampal Subfield Activation (Right Hemisphere)
The z-scores of hippocampal subregions and hemispheres represent the standardized difference in activation between correct and incorrect conditions of the mnemonic discrimination task, where a Z-score of 0 represents the mean difference across all voxels, and each unit reflects one standard deviation from that mean. To compare brain activation between conditions, separate beta weights were estimated for correct and incorrect trials across all trials. These beta weights represent the voxel-wise blood oxygen level (BOLD)-dependent signal, reflecting changes in neural activity associated with each condition. Positive z-scores indicate greater activation for correct relative to incorrect trials, whereas negative z-scores indicate greater activation for incorrect relative to correct trials. Larger absolute z-scores indicate stronger condition-related effects; there are no established clinical thresholds for these experimental activation differences.
Measured: 3 days
Hippocampal Subfield Volume (Left Hemisphere)
High resolution structural neuroimaging will be used to generate regional hippocampal subfield volume.
Measured: 3 days
Hippocampal Subfield Volume (Right Hemisphere)
High resolution structural neuroimaging will be used to generate regional hippocampal subfield volume.
Measured: 3 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2019
- Study start1 Oct 2019
- Primary completion16 Sep 2024
- Study completion16 Sep 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HydrocortisoneStudies of the same condition, open and under way.
- More trials run by University of Texas Southwestern Medical CenterThe 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 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 66 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Texas Southwestern Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sherwood Brown, MD, PhD, University of Texas Southwestern Medical Center
- Investigators
- Sherwood Brown, MD, PhD, Principal investigator, University of Texas Southwestern Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03896659
- Sponsor's protocol ID
- STU-2018-0360
- Other IDs
- 1R01MH115932-01A1
- Status last verified
- Dec 2025
- First submitted
- 28 Mar 2019
- Last updated
- 16 Dec 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Exploring the Effects of Corticosteroids on the Human Hippocampus Using Neurocognitive Testing and High Resolution Neuroimaging
- ClinicalTrials.gov ID
- NCT03896659
- Acronym / sponsor ID
- STU-2018-0360
- Conditions
- Hydrocortisone, Depression, Healthy Volunteers
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 66 participants (actual)
- Lead sponsor
- University of Texas Southwestern Medical CenterUniversity, hospital or other
- Collaborators
- University of California, Irvine, National Institute of Mental Health (NIMH)
- Study start
- 1 Oct 2019 (actual)
- Primary completion
- 16 Sep 2024 (actual)
- Study completion
- 16 Sep 2024 (actual)
- First posted
- 1 Apr 2019 (actual)
- Results
- Posted 16 Dec 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Depressed: Hydrocortisone, then Placebo | Experimental | Drug: Hydrocortisone Oral, Drug: Placebo Oral TabletParticipants 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. |
| Depressed: Placebo, then Hydrocortisone | Experimental | Drug: Hydrocortisone Oral, Drug: Placebo Oral TabletParticipants 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. |
| Healthy Controls: Hydrocortisone, then Placebo | Experimental | Drug: Hydrocortisone Oral, Drug: Placebo Oral TabletParticipants 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. |
| Healthy Controls: Placebo, then Hydrocortisone | Experimental | Drug: Hydrocortisone Oral, Drug: Placebo Oral TabletParticipants 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. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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)
Key exclusion criteria (11 listed)
- 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
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 |
|---|---|---|
| Hydrocortisone OralHydrocortisone 160 mg tablet | Drug | Depressed: Hydrocortisone, then Placebo, Depressed: Placebo, then Hydrocortisone, Healthy Controls: Hydrocortisone, then Placebo, Healthy Controls: Placebo, then Hydrocortisone |
| Placebo Oral TabletHydrocortisone-matched Placebo tablet | Drug | Depressed: Hydrocortisone, then Placebo, Depressed: Placebo, then Hydrocortisone, Healthy Controls: Hydrocortisone, then Placebo, Healthy Controls: Placebo, then Hydrocortisone |
Primary outcome
Hippocampal Subfield Activation (Left Hemisphere)
Time frame: 3 days
The z-scores of hippocampal subregions and hemispheres represent the standardized difference in activation between correct and incorrect conditions of the mnemonic discrimination task, where a Z-score of 0 represents the mean difference across all voxels, and each unit reflects one standard deviation from that mean. To compare brain activation between conditions, separate beta weights were estimated for correct and incorrect trials across all trials. These beta weights represent the voxel-wise blood oxygen level (BOLD)-dependent signal, reflecting changes in neural activity associated with each condition. Positive z-scores indicate greater activation for correct relative to incorrect trials, whereas negative z-scores indicate greater activation for incorrect relative to correct trials. Larger absolute z-scores indicate stronger condition-related effects; there are no established clinical thresholds for these experimental activation differences.
Hippocampal Subfield Activation (Right Hemisphere)
Time frame: 3 days
The z-scores of hippocampal subregions and hemispheres represent the standardized difference in activation between correct and incorrect conditions of the mnemonic discrimination task, where a Z-score of 0 represents the mean difference across all voxels, and each unit reflects one standard deviation from that mean. To compare brain activation between conditions, separate beta weights were estimated for correct and incorrect trials across all trials. These beta weights represent the voxel-wise blood oxygen level (BOLD)-dependent signal, reflecting changes in neural activity associated with each condition. Positive z-scores indicate greater activation for correct relative to incorrect trials, whereas negative z-scores indicate greater activation for incorrect relative to correct trials. Larger absolute z-scores indicate stronger condition-related effects; there are no established clinical thresholds for these experimental activation differences.
Hippocampal Subfield Volume (Left Hemisphere)
Time frame: 3 days
High resolution structural neuroimaging will be used to generate regional hippocampal subfield volume.
Hippocampal Subfield Volume (Right Hemisphere)
Time frame: 3 days
High resolution structural neuroimaging will be used to generate regional hippocampal subfield volume.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Dec 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
Sherwood Brown, MD, PhD principal investigator
University of Texas Southwestern Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Hydrocortisone Oral in people with Hydrocortisone and Depression, run by University of Texas Southwestern Medical Center 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 5 inclusion and 11 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: finished, as of the sponsor's last update on 16 Dec 2025. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Dec 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hippocampal Subfield Activation (Left Hemisphere) (time frame: 3 days). 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 16 Dec 2025.