Brain Receptor Function in Post-Traumatic Stress Disorder

NCT00046553 | Completed

• 2 other identifiers: 02031702-M-0317
• Study Type: observational
• Target: 97
• Locations: 1 country
• Sites: 1

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).

Conditions

Post-Traumatic Stress Disorder

Keywords

Cortisol; CRH; HPA Axis; Hypothalamus; Hippocampus; Post-Traumatic Stress Disorder; PTSD; Healthy Volunteer

Interventions

RU-486 (Mifepristone) DRUG

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): lead

Study Sites (1)

National Institute of Mental Health (NIMH)

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Yehuda R. Biology of posttraumatic stress disorder. J Clin Psychiatry. 2001;62 Suppl 17:41-6.

  PMID: 11495096 BACKGROUND

• Gesing 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.

  PMID: 11425909 BACKGROUND

• Bremner 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.

  PMID: 7793467 BACKGROUND

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Interventions

Mifepristone

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Design

• Study Type: observational
• Sponsor Type: NIH

Study Record Dates

• First Submitted: September 30, 2002
• First Posted: October 1, 2002
• Study Start: September 1, 2002
• Study Completion: October 1, 2004
• Last Updated: March 4, 2008

Record last verified: 2004-10

Locations

US (1)