Posttraumatic Stress Disorder (PTSD)Phase 4NCT00665678
Neural Correlates of Early Intervention for Posttraumatic Stress Disorder (PTSD)
A Phase 4 study testing paroxetine in people with Posttraumatic Stress Disorder (PTSD), run by Foundation for Atlanta Veterans Education and Research, Inc. at 1 site in United States.
Trial summary
Background: Innovation: Over 150,000 soldiers are currently deployed in Iraq as part of Operation Iraqi Freedom (OIF), and 12% of returning OIF veterans have posttraumatic stress disorder (PTSD). Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Posttraumatic Stress Disorder (PTSD)
- What is being tested?
- paroxetine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 160 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2008to Mar 2012
- Phase
- Phase 4
- 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 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Male and female veterans age 18-50
- Returned from Iraq Theater within the past six months
- Screen positive for PTSD related to Iraq deployment based on the PTSD Checklist
- Confirmed with PTSD based on the CAPS, including one month duration of symptoms
- Being discharged from active service from Iraq
- Provide written informed consent
Who cannot join
- History of loss of consciousness of more than one minute
- Psychotropic medication use within the previous four weeks
- History (based on the SCID) of lifetime or current alcohol or substance abuse/dependence, schizophrenia, schizoaffective disorder, or bipolar disorder.
- Positive urine toxicology screen
- History of pre-deployment-related PTSD or partial PTSD based on the CAPS
- History of PTSD or partial PTSD related to a prior deployment
Show all 12Show fewer
- Serious medical or neurological illness
- Pregnancy
- History of asthma
- Steroid usage, both inhaled and oral
- Seizure disorder
- Prenatal/perinatal substance exposure or trauma.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Neural Correlates of Early Intervention for PTSD
Background: Innovation: Over 150,000 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.
Objectives/Hypotheses: The objectives of this research are to:
Read more
- 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.
Read the detailed description
Study Design: Subjects returning from Iraq who meet criteria for early PTSD (N=160) 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.
- Conditions
- Posttraumatic Stress Disorder (PTSD)
- Being tested
- paroxetine, placebo
- 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.
paroxetineDrug
treatment for three months with paroxetine
placeboDrug
treatment for three months with placebo
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | paroxetine Receives: Drug: paroxetine |
| 2 | Placebo comparator | placebo Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
PTSD symptoms as measured with the CAPS
Measured: three months
Secondary outcomes (1)
Assess the effects of paroxetine versus placebo on amygdala metabolism and medial prefrontal response to stress in OIF veterans with PTSD.
Measured: three months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2008 (estimated)
- Study startApr 2008
- Primary completionMar 2012
- Study completionMar 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Posttraumatic Stress Disorder (PTSD)Studies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Foundation for Atlanta Veterans Education and Research, Inc.
- Sponsor type
- University, hospital or other
- Collaborators
- Emory University
- Investigators
- James D Bremner, MD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00665678
- Sponsor's protocol ID
- CDMRP PT074585
- Status last verified
- Jul 2012
- First submitted
- 22 Apr 2008
- Last updated
- 11 Jul 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 11 Jul 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neural Correlates of Early Intervention for PTSD
- ClinicalTrials.gov ID
- NCT00665678
- Acronym / sponsor ID
- CDMRP PT074585
- Conditions
- Posttraumatic Stress Disorder (PTSD)
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 160 participants (estimated)
- Lead sponsor
- Foundation for Atlanta Veterans Education and Research, Inc.University, hospital or other
- Collaborators
- Emory University
- Study start
- Apr 2008
- Primary completion
- Mar 2012 (actual)
- Study completion
- Mar 2012 (actual)
- First posted
- 24 Apr 2008 (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.
Background: Innovation: Over 150,000 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.
Objectives/Hypotheses: 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 (N=160) 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: paroxetineparoxetine |
| 2 | Placebo comparator | Drug: placeboplacebo |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Male and female veterans age 18-50
- Returned from Iraq Theater within the past six months
- Screen positive for PTSD related to Iraq deployment based on the PTSD Checklist
- Confirmed with PTSD based on the CAPS, including one month duration of symptoms
- Being discharged from active service from Iraq
Key exclusion criteria (12 listed)
- History of loss of consciousness of more than one minute
- Psychotropic medication use within the previous four weeks
- History (based on the SCID) of lifetime or current alcohol or substance abuse/dependence, schizophrenia, schizoaffective disorder, or bipolar disorder.
- Positive urine toxicology screen
- History of pre-deployment-related PTSD or partial PTSD based on the CAPS
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 |
|---|---|---|
| paroxetinetreatment for three months with paroxetine | Drug | 1 |
| placebotreatment for three months with placebo | Drug | 2 |
Primary outcome
PTSD symptoms as measured with the CAPS
Time frame: three months
1 secondary outcome
Assess the effects of paroxetine versus placebo on amygdala metabolism and medial prefrontal response to stress in OIF veterans with PTSD.
Time frame: three months
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jul 2012.
- Dr. Bremner's Home PageLink provided by the sponsor.
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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.
James D Bremner, MD principal investigator
Emory University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing paroxetine in people with Posttraumatic Stress Disorder (PTSD), run by Foundation for Atlanta Veterans Education and Research, Inc. 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 12 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: stopped early, as of the sponsor's last update on 11 Jul 2012. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early. Results are not available in the source record.
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?
PTSD symptoms as measured with the CAPS (time frame: three months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 11 Jul 2012.