Ignite Creation Date:
2024-05-05 @ 11:26 AM
Last Modification Date:
2024-10-26 @ 9:07 AM
Study NCT ID:
NCT00046553
Status:
COMPLETED
Last Update Posted:
2008-03-04
First Post:
2002-09-30
Brief Title:
Brain Receptor Function in Post-Traumatic Stress Disorder
Sponsor:
National Institute of Mental Health NIMH
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Glucocorticoid and Mineralocorticoid Receptor Function in Post Traumatic Stress Disorder
Status:
COMPLETED
Status Verified Date:
2004-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 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
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 andor 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 andor 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 MRGR 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
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 andor 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 MRGR 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 02-M-0317 | None | None | None |