Ignite Creation Date:
2024-05-05 @ 7:23 PM
Last Modification Date:
2024-10-26 @ 9:48 AM
Study NCT ID:
NCT00665678
Status:
TERMINATED
Last Update Posted:
2012-07-11
First Post:
2008-04-22
Brief Title:
Neural Correlates of Early Intervention for Posttraumatic Stress Disorder PTSD
Sponsor:
Foundation for Atlanta Veterans Education and Research Inc
Organization:
Foundation for Atlanta Veterans Education and Research Inc
Study Overview
Official Title:
Neural Correlates of Early Intervention for PTSD
Status:
TERMINATED
Status Verified Date:
2012-07
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:
Background Innovation Over 150000 soldiers are currently deployed in Iraq as part of Operation Iraqi Freedom OIF and 12 of returning OIF veterans have posttraumatic stress disorder PTSD Research from our group and others showed lasting neurobiological consequences of PTSD including increased amygdala function and decreased medial prefrontal function verbal declarative memory problems and smaller hippocampal volume that reverses with treatment with the serotonin reuptake inhibitor SSRI paroxetine or the anticonvulsant phenytoin Recently we found that three months of treatment with paroxetine in PTSD patients resulted in an increase in hippocampal N-acetyl-aspartate NAA a marker of neuronal integrity as well as decreased brain metabolism in the amygdala and a reversal or stress induced decreases in medial prefrontal function Subjects treated with placebo did not have an increase in NAA however subsequent treatment for three months with open label paroxetine resulted in an increase in NAA to the level seen in the subjects treated with paroxetine in the double-blind phase Paroxetine was associated with a decrease in amygdala metabolism measured with positron emission tomography PET and increased medial prefrontal function Intervening soon after the trauma is critical for long-term outcomes since with time traumatic memories become indelible and resistant to treatment Diminished efficacy of treatment over time is shown by the fact that trials of Vietnam veterans have shown less efficacy over the years Animal studies show that pretreatment before stress with antidepressants reduces chronic behavioral deficits related to stress although for ethical and other reasons no studies have provided pretreatment before trauma exposure in humans In our current VA Merit funded program we are looking at the effects of early interventions for Iraq soldiers with paroxetine looking at chronicity of PTSD cognition cortisol response to stress hippocampal volume and NAA as outcomes We now propose to add measurement of neural correlates of paroxetine response using PET
ObjectivesHypotheses The objectives of this research are to
Assess the efficacy of paroxetine versus placebo in the treatment of early PTSD in OIF veterans
Assess the effects of paroxetine versus placebo on amygdala metabolism and medial prefrontal response to stress in OIF veterans with PTSD
Assess the ability of brain imaging to predict treatment response and to identify veterans with early PTSD who will benefit from early interventions
Hypotheses are that paroxetine will be associated with 1 an improvement in PTSD symptoms compared to placebo based on the change in the CAPS from baseline to three months of treatment in veterans of OIF 2 increased medial prefrontal function and decreased amygdala metabolism in veterans of OIF
Specific Aims
Compare paroxetine to placebo in the treatment of early PTSD in OIF veterans
Measure amygdala metabolism and medial prefrontal response to stress with PET in OIF veterans with PTSD before and after paroxetine or placebo treatment
ObjectivesHypotheses The objectives of this research are to
Assess the efficacy of paroxetine versus placebo in the treatment of early PTSD in OIF veterans
Assess the effects of paroxetine versus placebo on amygdala metabolism and medial prefrontal response to stress in OIF veterans with PTSD
Assess the ability of brain imaging to predict treatment response and to identify veterans with early PTSD who will benefit from early interventions
Hypotheses are that paroxetine will be associated with 1 an improvement in PTSD symptoms compared to placebo based on the change in the CAPS from baseline to three months of treatment in veterans of OIF 2 increased medial prefrontal function and decreased amygdala metabolism in veterans of OIF
Specific Aims
Compare paroxetine to placebo in the treatment of early PTSD in OIF veterans
Measure amygdala metabolism and medial prefrontal response to stress with PET in OIF veterans with PTSD before and after paroxetine or placebo treatment
Detailed Description:
Study Design Subjects returning from Iraq who meet criteria for early PTSD N160 will be included in the study with a recruitment goal of 144 completers A group of 80 healthy subjects with a history of military service during the period of OIF without a history of deployment and without PTSD and 80 healthy subjects with a history of deployment without PTSD will serve as comparator groups All subjects will undergo baseline imaging of the brain with PET FDG and with measurement of brain blood flow during a memory task and with exposure to trauma related reminders slides and sounds and MRI and baseline psychometric assessments following which PTSD subjects will be randomized to receive paroxetine or placebo for three months with repeat imaging and assessments After this PTSD subjects will be treated with three months of open label paroxetine followed by a repeat of imaging and assessments This will be an intent to treat analysis therefore all subjects who were randomized and took at least one dose of study medication will be assessed at three months regardless of whether they were able to stay on study medication This will complement our currently VA Clinical Trial Merit funded application to measure hippocampal volume NAA and cortisol response to stress before and after early intervention with paroxetine in returning Iraq vets with early PTSD
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