DepressionDASHNCT03195933
Depression, Adversity, and Stress Hormones (DASH) Study
A study testing Cortisol in people with Depression, run by University of Wisconsin, Madison.
Trial summary
The stress-related hormone cortisol has been studied in depression for decades. However, relatively little is known about the role of cortisol in psychological features of depression. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Depression
- What is being tested?
- Cortisol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 85 participants
- Where
- No sites listed yet
- Study dates
- 31 Jul 2013to 19 May 2016
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 45 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Female
- 18 to 45 years of age
- English fluency
- Able to lie still on their back for up to 90 minutes
- Willing and able to return for all visits
- Able to provide written informed consent prior to participation
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- In good physical health as determined on basis of medical history
- If a nicotine user, able to refrain from nicotine use for 2 hours prior to fMRI scanning and throughout the scan visits
- Additional criteria for never-depressed participants: Free of current or past Diagnostic and Statistical Manual (DSM) IV diagnoses of Major Depressive Disorder (MDD), Dysthymia, or other Depressive Disorder. Never-depressed participants may have past or current psychopathology other than depressive disorders that does not cause significant impairment in functioning and that would not interfere with study participation, be exacerbated by study participation, or introduce scientific difficulties, for example, history of complicated bereavement or history of time-limited alcohol abuse that does not represent a lasting substance use disorder
- Additional criteria for participants with MDD: Meet DSM-IV criteria for MDD (single or recurrent) as determined by a Structured Clinical Interview for DSM-IV (SCID)
- Additional criteria for depression-prone participants: Does not meet criteria for current MDD, but meets at least one of the following requirements:
- Meets DSM-IV criteria for past MDD (single or recurrent) as determined by a SCID interview
- Meets DSM-IV criteria for Depressive Disorder Not Otherwise Specified (NOS)
- Meets DSM-IV criteria for Dysthymia
- Has a Beck Depression Inventory (BDI) score of 14 or higher
Who cannot join
- Current use of any anti-depressant or psychotropic medication while participating in Visits 1-6 and Home Saliva Collection; treatment with electroconvulsive therapy (ECT) within the past 3 months; use of any anti-depressant within 14 days of participation, fluoxetine within 30 days of participation, or any other psychotropic drug within a timeframe based on the half-life of the particular drug
- Using hormonal contraceptives while participating in Visits 1-6 and Home Saliva Collection
- Using any medication that affects central nervous system (CNS) function for 2-4 weeks prior to testing and during participation in Visits 1-6 and Home Saliva Collection
- Using any illicit drug for 4 weeks prior to testing and during participation in Visits 1-6 and Home Saliva Collection
- Using any steroid, anti-histamine, nasal spray (which includes corticosteroids), or topical hydrocortisone cream/gel that affects the hypothalamic-pituitary-adrenal (HPA) axis for 2-4 weeks prior to testing and throughout the duration of the study
- History of seizures, diabetes, hypertension, neurological problems, and/or cardiac problems
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- Metallic implants (i.e., prostheses, shrapnel, or aneurysm clips) or electronic implants (i.e., cardiac pacemakers) that are contraindicated for MRI
- Any clinically significant abnormalities on medical history or physical exam
- Currently pregnant, trying to become pregnant, breastfeeding, within a six-month window following pregnancy or breastfeeding, sexually active without an acceptable method of birth control (e.g., abstinence, male vasectomy, female sterilization, condom)
- Post-menopausal and peri-menopausal women
- Women with highly irregular menstrual cycles (e.g., more than 60 days between periods or less than 14 days between periods)
- Individuals who work the "night shift" (e.g., between the hours of 11 pm and 7 am) will be excluded due to potential variability in cortisol levels determined by sleep schedule
- Heavy nicotine user (e.g., smokes more than a pack/day)
- Unable to fit comfortably in the MRI simulator and/or scanner (e.g., BMI greater than approx. 38)
- Weight greater than approx. 250 lbs
- Lifetime history of mania or psychosis
- At risk for suicide as determined by a clinical interview
- Gross impairment in functioning
- Claustrophobia
- Frank Axis I or Axis II psychopathology that would interfere with study participation, become exacerbated by study participation, or introduce scientific difficulties
About this study
Official title: Learning, Neural Signaling of Cortisol, and Early Adversity in Depression
The stress-related hormone cortisol has been studied in depression for decades. However, relatively little is known about the role of cortisol in psychological features of depression. Basic research shows that cortisol modulates brain processes that are highly relevant to depression (especially the neural substrates of negative biases in learning and memory formation). However, very few studies have directly examined the effects of cortisol on neural circuitry of learning in depressed humans. In addition, the effects of cortisol on the neural substrates of learning differ for males and females. The toll of depression is especially high in women, who are roughly twice as likely as men to suffer from depression. Thus, the primary goal of this project is to investigate the effects of cortisol on the neural circuitry of learning in depressed women.
A secondary goal is to investigate whether early life adversity moderates cortisol's effects on the neural circuitry of learning. Animal data suggests that early life adversity causes life-long biases toward learning in threatening conditions associated with elevated cortisol. In addition, new data from humans suggests that alterations in cortisol traditionally ascribed to depression may stem in part from early adversity rather than depression per se. Thus, this study will examine effects of cortisol on the neural circuitry of learning in depressed and healthy women with and without history of early life adversity.
Read more
The study will use pharmacological manipulation of cortisol levels (compared to placebo) during measurement of brain activity at rest and during memory encoding of emotional and neutral stimuli. The study will also measure whether cortisol alters the negative biases in emotional memory often seen in depression. In doing so, the study will examine the role of cortisol in neural networks associated with emotional learning that are often implicated in depression.
Medications that target cortisol receptors in the brain may be beneficial in the treatment of depression. However, this knowledge has yet to inform clinical practice, and mechanisms of action of these medications are not well understood. This project is significant because it provides the prerequisite knowledge (and develops a paradigm) that can be used in the future in the development of more effective targeted intervention strategies.
- Conditions
- Depression
- Being tested
- Cortisol, Placebo
- Keywords
- Depression, Childhood Adversity, Childhood Abuse, Cortisol, Emotional Memory, Magnetic Resonance Imaging (MRI)
- Medical subject headings
- Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CortisolOther
We compared placebo vs. 20 mg oral dose of cortisol, which pharmacologically elevated cortisol levels.
PlaceboOther
We compared placebo vs. 20 mg oral dose of cortisol, which pharmacologically elevated cortisol levels.
| Study group | Role | What they receive |
|---|---|---|
| Cortisol first, Placebo second | Experimental | Single oral administration of 20 mg cortisol capsule to pharmacologically elevate cortisol levels during first functional magnetic resonance imaging (fMRI) session; Identically appearing placebo capsule during second fMRI session. Receives: Other: Cortisol; Other: Placebo |
| Placebo first, Cortisol second | Experimental | Placebo capsule during first fMRI session; Single oral administration of 20 mg cortisol capsule to pharmacologically elevate cortisol levels during second fMRI session. Receives: Other: Cortisol; Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Emotional Memory after Cortisol Administration
Memory for emotional pictures encoded during the cortisol administration MRI scan
Measured: 15 minute memory assessment that takes place 2 days after cortisol administration MRI scan visit
Secondary outcomes (1)
Neural Function
MRI
Measured: 90 minute scan session
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2017
- Study start31 Jul 2013
- Primary completion19 May 2016
- Study completion19 May 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for DepressionStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 85 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Wisconsin, Madison
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH), Brain & Behavior Research Foundation
- Responsible party
- Sponsor
- Investigators
- Heather C. Abercrombie, Ph.D., Principal investigator, University of Wisconsin School of Medicine & Public Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03195933
- Sponsor's protocol ID
- 2011-0897
- Other IDs
- R01MH094478
- Acronym
- DASH
- Status last verified
- Jun 2017
- First submitted
- 19 Jun 2017
- Last updated
- 22 Jun 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: We will make our data publicly available on a password protected website after the data are collected and analyzed, and manuscripts presenting data testing our hypotheses are accepted for publication. These data will be thoroughly de-identified. Several classes of data will be made available, including self-report, behavioral, diagnostic, hormonal, and summary data from our physiological and imaging datasets.
Publications
Gaffey AE, Walsh EC, Ladd CO, Hoks RM, Abercrombie HC. Alterations in Systemic and Cognitive Glucocorticoid Sensitivity in Depression. Biol Psychiatry Cogn Neurosci Neuroimaging. 2019 Mar;4(3):310-320. doi: 10.1016/j.bpsc.2018.11.007. Epub 2018 Dec 4.
PubMed 30686583Abercrombie HC, Frost CP, Walsh EC, Hoks RM, Cornejo MD, Sampe MC, Gaffey AE, Plante DT, Ladd CO, Birn RM. Neural Signaling of Cortisol, Childhood Emotional Abuse, and Depression-Related Memory Bias. Biol Psychiatry Cogn Neurosci Neuroimaging. 2018 Mar;3(3):274-284. doi: 10.1016/j.bpsc.2017.11.005. Epub 2017 Nov 22.
PubMed 29486869
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Learning, Neural Signaling of Cortisol, and Early Adversity in Depression
- ClinicalTrials.gov ID
- NCT03195933
- Acronym / sponsor ID
- DASH / 2011-0897
- Conditions
- Depression
- Keywords
- Depression, Childhood Adversity, Childhood Abuse, Cortisol, Emotional Memory, Magnetic Resonance Imaging (MRI)
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 85 participants (actual)
- Lead sponsor
- University of Wisconsin, MadisonUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH), Brain & Behavior Research Foundation
- Study start
- 31 Jul 2013 (actual)
- Primary completion
- 19 May 2016 (actual)
- Study completion
- 19 May 2016 (actual)
- First posted
- 22 Jun 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The stress-related hormone cortisol has been studied in depression for decades. However, relatively little is known about the role of cortisol in psychological features of depression. Basic research shows that cortisol modulates brain processes that are highly relevant to depression (especially the neural substrates of negative biases in learning and memory formation). However, very few studies have directly examined the effects of cortisol on neural circuitry of learning in depressed humans. In addition, the effects of cortisol on the neural substrates of learning differ for males and females. The toll of depression is especially high in women, who are roughly twice as likely as men to suffer from depression. Thus, the primary goal of this project is to investigate the effects of cortisol on the neural circuitry of learning in depressed women.
A secondary goal is to investigate whether early life adversity moderates cortisol's effects on the neural circuitry of learning. Animal data suggests that early life adversity causes life-long biases toward learning in threatening conditions associated with elevated cortisol. In addition, new data from humans suggests that alterations in cortisol traditionally ascribed to depression may stem in part from early adversity rather than depression per se. Thus, this study will examine effects of cortisol on the neural circuitry of learning in depressed and healthy women with and without history of early life adversity.
The study will use pharmacological manipulation of cortisol levels (compared to placebo) during measurement of brain activity at rest and during memory encoding of emotional and neutral stimuli. The study will also measure whether cortisol alters the negative biases in emotional memory often seen in depression. In doing so, the study will examine the role of cortisol in neural networks associated with emotional learning that are often implicated in depression.
Medications that target cortisol receptors in the brain may be beneficial in the treatment of depression. However, this knowledge has yet to inform clinical practice, and mechanisms of action of these medications are not well understood. This project is significant because it provides the prerequisite knowledge (and develops a paradigm) that can be used in the future in the development of more effective targeted intervention strategies.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cortisol first, Placebo second | Experimental | Other: Cortisol, Other: PlaceboSingle oral administration of 20 mg cortisol capsule to pharmacologically elevate cortisol levels during first functional magnetic resonance imaging (fMRI) session; Identically appearing placebo capsule during second fMRI session. |
| Placebo first, Cortisol second | Experimental | Other: Cortisol, Other: PlaceboPlacebo capsule during first fMRI session; Single oral administration of 20 mg cortisol capsule to pharmacologically elevate cortisol levels during second fMRI session. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (15 listed)
- Female
- 18 to 45 years of age
- English fluency
- Able to lie still on their back for up to 90 minutes
- Willing and able to return for all visits
Key exclusion criteria (20 listed)
- Current use of any anti-depressant or psychotropic medication while participating in Visits 1-6 and Home Saliva Collection; treatment with electroconvulsive therapy (ECT) within the past 3 months; use of any anti-depressant within 14 days of participation, fluoxetine within 30 days of participation, or any other psychotropic drug within a timeframe based on the half-life of the particular drug
- Using hormonal contraceptives while participating in Visits 1-6 and Home Saliva Collection
- Using any medication that affects central nervous system (CNS) function for 2-4 weeks prior to testing and during participation in Visits 1-6 and Home Saliva Collection
- Using any illicit drug for 4 weeks prior to testing and during participation in Visits 1-6 and Home Saliva Collection
- Using any steroid, anti-histamine, nasal spray (which includes corticosteroids), or topical hydrocortisone cream/gel that affects the hypothalamic-pituitary-adrenal (HPA) axis for 2-4 weeks prior to testing and throughout the duration of the study
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 |
|---|---|---|
| CortisolWe compared placebo vs. 20 mg oral dose of cortisol, which pharmacologically elevated cortisol levels. | Other | Cortisol first, Placebo second, Placebo first, Cortisol second |
| PlaceboWe compared placebo vs. 20 mg oral dose of cortisol, which pharmacologically elevated cortisol levels. | Other | Cortisol first, Placebo second, Placebo first, Cortisol second |
Primary outcome
Emotional Memory after Cortisol Administration
Time frame: 15 minute memory assessment that takes place 2 days after cortisol administration MRI scan visit
Memory for emotional pictures encoded during the cortisol administration MRI scan
1 secondary outcome
Neural Function
Time frame: 90 minute scan session
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2017.
- Derived from this study: PubMed 30686583Gaffey AE, Walsh EC, Ladd CO, Hoks RM, Abercrombie HC. Alterations in Systemic and Cognitive Glucocorticoid Sensitivity in Depression. Biol Psychiatry Cogn Neurosci Neuroimaging. 2019 Mar;4(3):310-320. doi: 10.1016/j.bpsc.2018.11.007. Epub 2018 Dec 4.
- Derived from this study: PubMed 29486869Abercrombie HC, Frost CP, Walsh EC, Hoks RM, Cornejo MD, Sampe MC, Gaffey AE, Plante DT, Ladd CO, Birn RM. Neural Signaling of Cortisol, Childhood Emotional Abuse, and Depression-Related Memory Bias. Biol Psychiatry Cogn Neurosci Neuroimaging. 2018 Mar;3(3):274-284. doi: 10.1016/j.bpsc.2017.11.005. Epub 2017 Nov 22.
- Individual participant dataSharing planned: Yes. We will make our data publicly available on a password protected website after the data are collected and analyzed, and manuscripts presenting data testing our hypotheses are accepted for publication. These data will be thoroughly de-identified. Several classes of data will be made available, including self-report, behavioral, diagnostic, hormonal, and summary data from our physiological and imaging datasets.
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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.
Heather C. Abercrombie, Ph.D. principal investigator
University of Wisconsin School of Medicine & Public Health
Questions about this trial
What is this clinical trial studying?
A study testing Cortisol in people with Depression, run by University of Wisconsin, Madison.
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 15 inclusion and 20 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 22 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Emotional Memory after Cortisol Administration (time frame: 15 minute memory assessment that takes place 2 days after cortisol administration MRI scan visit). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03195933, which also lists 2 linked publications.
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 22 Jun 2017.