Post-Traumatic Stress DisorderNCT00046553
Brain Receptor Function in Post-Traumatic Stress Disorder
An observational study of Post-Traumatic Stress Disorder, run by National Institute of Mental Health (NIMH) at 1 site in United States.
Trial summary
The purpose of this study is to examine the function of cortisol receptors in post-traumatic stress disorder (PTSD). Patients with PTSD have neurobiological dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis function. Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Post-Traumatic Stress Disorder
- What is being tested?
- RU-486 (Mifepristone)
- How many people
- 97 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2002to Oct 2004
- Phase
- Observational
- 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 Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- 18 to 65 years of age.
- Male and female.
- Score greater than or equal to 50 on the Clinician-Administered PTSD Scale (CAPS-2) as a baseline measure of PTSD symptom severity.
- Capable of providing informed consent, obtained prior to any study procedures.
- Free of all psychotropic medication for at least 2 weeks, excluding short-term hypnotics. Patients who were treated with fluoxetine will only be included after a medication free period of at least 8 weeks.
- Good physical health, confirmed by a complete physical exam (including normal vital signs), electrocardiogram, neurologic exam, and routine laboratory tests of blood and urine. However, if patients have participated in other research studies or have had blood work through their primary MD within the last 6 months, these results will be used instead of repeating blood draws for inclusion into the study.
Who cannot join
- Patients who meet DSM-IV criteria for substance abuse (alcohol or drugs) or substance dependence within 6 months prior to screening. The effect of abuse/dependence on phenomenology and biology could mask and exceed PTSD effect.
- Patients at current risk for homicide or suicide.
- All additional DSM IV Axis I comorbidity, excluding secondary diagnoses of major depressive disorder (MDD) or anxiety disorder (AD). Given the high comorbidity of these disorders in PTSD, and since excluding such patients would not provide the full spectrum of the disorder, only patients in whom axis I diagnoses of MDD and AD preceded onset of PTSD will be excluded.
- Pregnant women (all stages) and women of childbearing potential who are not practicing a clinically accepted method of contraception or who have a positive pregnancy test or who are lactating.
- Blood donation (1 Red Cross Unit) within the 8 weeks preceding the study. This is the minimal safe period between consecutive donations.
- Subjects who are doing well on medication. Although we will only recruit non-medicated patients, the decision to stop medication will be taken purely on clinical grounds. No subject will be taken off medication solely to participate in the study.
- Unable to comply with study procedures or assessments as regards the screening evaluation (i.e. PTSD diagnosis, health requirements, etc.) and the 3 hospitalization for evaluation of glucocorticoid and mineralocorticoid receptor function.
- Subjects who are allergic to mifepristone, paroxetine or spironolactone, and subjects with any contraindication to treatment with these agents (as described in their current labeling), will be excluded from participation in the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute of Mental Health (NIMH)
Bethesda, Maryland, 20892
About this study
Official title: Glucocorticoid and Mineralocorticoid Receptor Function in Post Traumatic Stress Disorder
The purpose of this study is to examine the function of cortisol receptors in post-traumatic stress disorder (PTSD).
Patients with PTSD have neurobiological dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis function. High corticotrophin releasing hormone (CRH) levels and decreased hippocampal volume are major features of the disorder. The mechanisms responsible for these alterations are not known. This study will evaluate the function of cortisol receptors to determine their roles in maintaining PTSD HPA axis dysregulation. Three groups of subjects will take part in the study: Patients with PTSD, healthy control subjects who were exposed to trauma in the past and remained healthy and healthy control subjects who were never traumatized
Read more
At study entry, the cerebral spinal fluid (CSF) of all participants will be sampled and evaluated. Participants will also undergo a magnetic resonance imaging (MRI) scan of the brain as well as eye blink trace conditioning and neuropsychological tests.
Participants will be admitted to the Clinical Center for two nights on three different occasions. At each overnight visits, blood levels of stress hormones will be measured every hour for 26 hours after medication or placebo are given. This will be the end of the study for both groups of healthy control subjects, with the exception that they may be asked to repeat neuropsychologic and eye blink tests after 12 weeks.
Participants with PTSD will receive paroxetine for 10 weeks. After 10 weeks these participants will be reevaluated in exactly the same way as before treatment (except they will not repeat the MRI scan).
Read the detailed description
We propose to investigate the underlying mechanisms that account for neurobiological dysregulation of HPA axis function in PTSD. Paradoxically, low or normal plasma and urinary cortisol despite high corticotrophin releasing hormone (CRH) levels are a major feature of this disorder. Some investigators report decreased hippocampal volume in patients with PTSD. The mechanisms responsible for these alterations are not known. One possibility is that patients with PTSD have an increased number of glucocorticoid receptors (GR) and/or increased GR sensitivity, causing hyper-suppression of HPA axis. Another possibility is that high CRH levels lead to increased mineralocorticoid receptor (MR) levels and this up-regulation of MR is responsible for the low cortisol secretion seen in PTSD. Elevated CRH levels could also result in reduced hippocampal volume.
In order to evaluate MR and GR function, we will examine the effect of RU486 (Mifepristone; a GR antagonist), spironolactone (Aldactone; an MR antagonist), and placebo, on cortisol and ACTH plasma levels in patients with PTSD, trauma exposed, and non-trauma exposed healthy controls. The extent of increase in cortisol and/or ACTH after administration of antagonists will reflect the inhibition ordinarily imposed by GR and MR. We will also examine subjects' cerebral spinal fluid (CSF), CRH levels, and hippocampal volume. Following this evaluation, patients with PTSD will be treated with paroxetine for 8 weeks. The assessments performed before treatment will then be repeated.
The first aim of the present study is to elucidate the pathophysiology of PTSD through the examination of the roles of GR and MR in maintaining PTSD HPA axis dysregulation. The second aim is to compare CSF CRH levels across groups in an effort to extend previous findings and determine whether CRH levels in PTSD are higher than levels in trauma exposed healthy subjects. The present investigation will also evaluate the relationship between CRH levels in PTSD, MR/GR function, hippocampal volume and hippocampally-mediated cognitive tasks. Finally, we will examine the effects of long-term paroxetine treatment in PTSD on HPA axis function, hippocampal volume, and hippocampally-mediated cognitive tasks.
- Conditions
- Post-Traumatic Stress Disorder
- Being tested
- RU-486 (Mifepristone)
- Keywords
- Cortisol, CRH, HPA Axis, Hypothalamus, Hippocampus, Post-Traumatic Stress Disorder, PTSD, Healthy Volunteer
- Medical subject headings
- Stress Disorders, Post-Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RU-486 (Mifepristone)Drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2002 (estimated)
- Study startSep 2002
- Study completionOct 2004
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Post-Traumatic Stress DisorderStudies of the same condition, open and under way.
- More trials run by National Institute of Mental Health (NIMH)The 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
- Observational
- Enrolment
- 97 participants
Sponsor and investigators
- Lead sponsor
- National Institute of Mental Health (NIMH)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00046553
- Sponsor's protocol ID
- 020317
- Other IDs
- 02-M-0317
- Status last verified
- Oct 2004
- First submitted
- 30 Sep 2002
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Yehuda R. Biology of posttraumatic stress disorder. J Clin Psychiatry. 2001;62 Suppl 17:41-6.
PubMed 11495096Gesing A, Bilang-Bleuel A, Droste SK, Linthorst AC, Holsboer F, Reul JM. Psychological stress increases hippocampal mineralocorticoid receptor levels: involvement of corticotropin-releasing hormone. J Neurosci. 2001 Jul 1;21(13):4822-9. doi: 10.1523/JNEUROSCI.21-13-04822.2001.
PubMed 11425909Bremner JD, Randall P, Scott TM, Bronen RA, Seibyl JP, Southwick SM, Delaney RC, McCarthy G, Charney DS, Innis RB. MRI-based measurement of hippocampal volume in patients with combat-related posttraumatic stress disorder. Am J Psychiatry. 1995 Jul;152(7):973-81. doi: 10.1176/ajp.152.7.973.
PubMed 7793467
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Glucocorticoid and Mineralocorticoid Receptor Function in Post Traumatic Stress Disorder
- ClinicalTrials.gov ID
- NCT00046553
- Acronym / sponsor ID
- 020317
- Conditions
- Post-Traumatic Stress Disorder
- Keywords
- Cortisol, CRH, HPA Axis, Hypothalamus, Hippocampus, Post-Traumatic Stress Disorder, PTSD, Healthy Volunteer
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 97 participants
- Lead sponsor
- National Institute of Mental Health (NIMH)US National Institutes of Health
- Study start
- Sep 2002
- Study completion
- Oct 2004
- First posted
- 1 Oct 2002 (estimated)
- 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 purpose of this study is to examine the function of cortisol receptors in post-traumatic stress disorder (PTSD).
Patients with PTSD have neurobiological dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis function. High corticotrophin releasing hormone (CRH) levels and decreased hippocampal volume are major features of the disorder. The mechanisms responsible for these alterations are not known. This study will evaluate the function of cortisol receptors to determine their roles in maintaining PTSD HPA axis dysregulation. Three groups of subjects will take part in the study: Patients with PTSD, healthy control subjects who were exposed to trauma in the past and remained healthy and healthy control subjects who were never traumatized
At study entry, the cerebral spinal fluid (CSF) of all participants will be sampled and evaluated. Participants will also undergo a magnetic resonance imaging (MRI) scan of the brain as well as eye blink trace conditioning and neuropsychological tests.
Participants will be admitted to the Clinical Center for two nights on three different occasions. At each overnight visits, blood levels of stress hormones will be measured every hour for 26 hours after medication or placebo are given. This will be the end of the study for both groups of healthy control subjects, with the exception that they may be asked to repeat neuropsychologic and eye blink tests after 12 weeks.
Participants with PTSD will receive paroxetine for 10 weeks. After 10 weeks these participants will be reevaluated in exactly the same way as before treatment (except they will not repeat the MRI scan).
Detailed description
We propose to investigate the underlying mechanisms that account for neurobiological dysregulation of HPA axis function in PTSD. Paradoxically, low or normal plasma and urinary cortisol despite high corticotrophin releasing hormone (CRH) levels are a major feature of this disorder. Some investigators report decreased hippocampal volume in patients with PTSD. The mechanisms responsible for these alterations are not known. One possibility is that patients with PTSD have an increased number of glucocorticoid receptors (GR) and/or increased GR sensitivity, causing hyper-suppression of HPA axis. Another possibility is that high CRH levels lead to increased mineralocorticoid receptor (MR) levels and this up-regulation of MR is responsible for the low cortisol secretion seen in PTSD. Elevated CRH levels could also result in reduced hippocampal volume.
In order to evaluate MR and GR function, we will examine the effect of RU486 (Mifepristone; a GR antagonist), spironolactone (Aldactone; an MR antagonist), and placebo, on cortisol and ACTH plasma levels in patients with PTSD, trauma exposed, and non-trauma exposed healthy controls. The extent of increase in cortisol and/or ACTH after administration of antagonists will reflect the inhibition ordinarily imposed by GR and MR. We will also examine subjects' cerebral spinal fluid (CSF), CRH levels, and hippocampal volume. Following this evaluation, patients with PTSD will be treated with paroxetine for 8 weeks. The assessments performed before treatment will then be repeated.
The first aim of the present study is to elucidate the pathophysiology of PTSD through the examination of the roles of GR and MR in maintaining PTSD HPA axis dysregulation. The second aim is to compare CSF CRH levels across groups in an effort to extend previous findings and determine whether CRH levels in PTSD are higher than levels in trauma exposed healthy subjects. The present investigation will also evaluate the relationship between CRH levels in PTSD, MR/GR function, hippocampal volume and hippocampally-mediated cognitive tasks. Finally, we will examine the effects of long-term paroxetine treatment in PTSD on HPA axis function, hippocampal volume, and hippocampally-mediated cognitive tasks.
Study design
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- 18 to 65 years of age.
- Male and female.
- Score greater than or equal to 50 on the Clinician-Administered PTSD Scale (CAPS-2) as a baseline measure of PTSD symptom severity.
- Capable of providing informed consent, obtained prior to any study procedures.
- Free of all psychotropic medication for at least 2 weeks, excluding short-term hypnotics. Patients who were treated with fluoxetine will only be included after a medication free period of at least 8 weeks.
Key exclusion criteria (8 listed)
- Patients who meet DSM-IV criteria for substance abuse (alcohol or drugs) or substance dependence within 6 months prior to screening. The effect of abuse/dependence on phenomenology and biology could mask and exceed PTSD effect.
- Patients at current risk for homicide or suicide.
- All additional DSM IV Axis I comorbidity, excluding secondary diagnoses of major depressive disorder (MDD) or anxiety disorder (AD). Given the high comorbidity of these disorders in PTSD, and since excluding such patients would not provide the full spectrum of the disorder, only patients in whom axis I diagnoses of MDD and AD preceded onset of PTSD will be excluded.
- Pregnant women (all stages) and women of childbearing potential who are not practicing a clinically accepted method of contraception or who have a positive pregnancy test or who are lactating.
- Blood donation (1 Red Cross Unit) within the 8 weeks preceding the study. This is the minimal safe period between consecutive donations.
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 |
|---|---|---|
| RU-486 (Mifepristone) | Drug | – |
Primary outcome
Not reported in the source record.
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 4 Mar 2008.
- Background: PubMed 11495096Yehuda R. Biology of posttraumatic stress disorder. J Clin Psychiatry. 2001;62 Suppl 17:41-6.
- Background: PubMed 11425909Gesing A, Bilang-Bleuel A, Droste SK, Linthorst AC, Holsboer F, Reul JM. Psychological stress increases hippocampal mineralocorticoid receptor levels: involvement of corticotropin-releasing hormone. J Neurosci. 2001 Jul 1;21(13):4822-9. doi: 10.1523/JNEUROSCI.21-13-04822.2001.
- Background: PubMed 7793467Bremner JD, Randall P, Scott TM, Bronen RA, Seibyl JP, Southwick SM, Delaney RC, McCarthy G, Charney DS, Innis RB. MRI-based measurement of hippocampal volume in patients with combat-related posttraumatic stress disorder. Am J Psychiatry. 1995 Jul;152(7):973-81. doi: 10.1176/ajp.152.7.973.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Post-Traumatic Stress Disorder, run by National Institute of Mental Health (NIMH) 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 6 inclusion and 8 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 4 Mar 2008. 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.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00046553, which also lists 3 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 4 Mar 2008.