PTSDPhase 3MTGNCT00403455
Monoamine Transporters Genotypes: Risk of PTSD and Related Comorbidities
A Phase 3 study testing Paroxetine in people with PTSD, run by VA Office of Research and Development at 1 site in United States.
Trial summary
Dr. Wang's merit review is aimed at providing a better understanding of the relationship between SLC6A3/SLC6A4 and the mental health of veterans exposed to high levels of combat stress, specifically focusing on PTSD symptoms, related co-morbidities, treatment outcomes and seeks new approaches to therapy for our… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- PTSD
- What is being tested?
- Paroxetine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2006to Jul 2011
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Male and female combat veterans ages 18 years and older who meet DSM-III-R criteria for principle diagnosis of PTSD as determined by the CAP-S;
- A minimum 6-month duration of PTSD illness; 3)CGI-S score of 4 or higher and a total CAPS-2 severity score of 50 or higher at the baseline visit;
- Homozygous for either the S/S or L/L 5-HTT;
- Females must not be pregnant or lactating and must agree to an acceptable form of contraception while receiving study medication and for 1 month after.
Who cannot join
- Presence of any other primary axis I disorder (concurrent depression will be permitted if it is judged to be secondary to development for PTSD);
- Suicide ideation or attempts within the past 3 months;
- Alcohol or substance abuse or dependence in the past six months;
- Evidence of clinically significant hepatic or renal disease;
- Previous seizure disorder or condition predisposing to seizures, or on medications that might lower the seizure threshold
- Any acute or unstable medical condition that might interfere with the safe conduct of the study;
Show all 10Show fewer
- Intolerance or hypersensitivity to citalopram or any other SSRI;
- Treatment with a monoamine oxidase inhibitor within 14 days of initiating the study;
- Concomitant treatment with serotonin agonists, other SSRIs, meperidine, tramadol or other medication as determined by the study clinician.
- PTSD symptoms in need of immediate treatment as determined by clinical assessment from a psychiatrist not affiliated with the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
Ralph H. Johnson VA Medical Center, Charleston, SC
Charleston, South Carolina, 29401-5799
About this study
Dr. Wang's merit review is aimed at providing a better understanding of the relationship between SLC6A3/SLC6A4 and the mental health of veterans exposed to high levels of combat stress, specifically focusing on PTSD symptoms, related co-morbidities, treatment outcomes and seeks new approaches to therapy for our Veteran population.
Read the detailed description
Background: Post-traumatic Stress Disorder (PTSD), a debilitating condition that develops following exposure to trauma, is highly prevalent in military personnel and veterans due to high risk of trauma exposure in combat. Trauma exposure, as an environmental insult, is necessary, but itself is not sufficient to cause PTSD, since not everyone exposure to trauma develops PTSD. Brain dopamine (DAT) and serotonin (5-HTT) transporter play a critical role in the regulation of stress related psychological and behavioral functions. Genetic polymorphisms that affect 5-HTT and DAT function, such as the 5' promote polymorphism in the 5-HTT gene (SLC6A4)(5-HTTlpr) and 3' -untranslated region (UTR)-40 bp-variable number tandem repeat (VNTR)of DAT gene (SLC6A3), could influence individual susceptibility to trauma-related psychopathology.
Objective/Hypothesis: The objective of this application is to investigated the relationship between SLC6A3/SLC6A4 and the mental health of veterans exposed to high levels of combat stress, specifically focusing on PTSD symptoms, related comorbidities, and treatment outcome. The central hypothesis is that specific genetic variants that adversely affect serotonin and dopamine neurotransmission constitute a risk for the emergence of PTSD and related comorbid symptoms after trauma exposure; and, some of these variants may further influence PTSD and related response.
Specific Objectives: (1) To determine specific 5-HTTLPR genotype involvement in PTSD symptomatology, (2) to determine influence of combined SLC6A3/SLC6A4 genotypes on PTSD with substance dependence, (3)to identify 5 HTTLPR alleles that affect PTSD symptomatology and treatment outcome, and (4)to identify additional SLC6A3/SLC6A4 alleles associated with PTSD and related comorbidities.
Study Design: We have generated some preliminary data supporting our hypothesis by examining 5-HTTLPR and the 3'-UTR-VNTR of SLC6A3 genotypes in 109 combat veterans with and without PTSD. In this proposal, we will expand on these findings by recruiting 300 veterans exposed to sufficient combat stress defined by Combat Exposure Scale(CES) score of >10 and who qualify for DSM-IV category A PTSD diagnostic criteria, including approximately 150 veterans with PTSD veterans with PTSD defined using DSM-IV diagnostic criteria, Clinician Administered PTSD Scale (CAPS) score >45 and 150 healthy combat-exposed veterans as defined by a CAPS score <15. We will first apply a newly developed extreme discordant phenotype (EDP) method to examine how 5-HTTLPR and 3'-UTR-VNTR genotypes affect trauma related psychopathology in combat veterans only with the highest (>45)and lowest (<15) CAPS scores. Secondly, single nucleotide polymorphisms (SNPs)will be examined across both genes and assessed for relatedness to PTSD susceptibility or resistance. Further analyses of relationship of these polymorphisms with comorbidities will also be performed. Thirdly, a pharmacogenetic trail (using sertraline as a therapeutic agent) will be applied to assess how gene variants influence PTSD treatment outcome. To Safeguard against population stratification, a genome control method will be applied in all the genetic analyses.
- Conditions
- PTSD
- Being tested
- Paroxetine
- Keywords
- Clinical, Genetics, Monoamine transporter, Pharmacogenetics, Post Traumatic Stress Disorder
- 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
Also called Paxil
SSRI
| Study group | Role | What they receive |
|---|---|---|
| Paroxetine Arm | Other | This is a single arm, single site, open-label clinical trial to treat veterans with PTSD. It is a 12-week trial to investigate the efficacy of paroxetine in reducing PTSD symptoms, with the primary outcome measure using CAPS. Genetic information is included to understand why some respond and some do not respond to paroxetine treatment. Receives: Drug: Paroxetine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinician Administered PTSD Scale (CAPS)
The CAPS assessment is used to determine the severity of an individuals PTSD. The assessment examines Re-experiencing, Avoidance and Numbing, and Hyperarousal symptoms which total score in each of these categories are added together to achieve a total CAPS score. Scores on this assessment can range from 0-136 with 0 not having any PTSD symptoms and 136 having the most symptoms possible. The study uses this assessment at the baseline and at the end of treatment to determine the decrease in this score over the course of the study.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Nov 2006 (estimated)
- Study startOct 2006
- Primary completionJul 2011
- Study completionJul 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for PTSDStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe 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
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Zhewu Wang, MD, Principal investigator, Ralph H. Johnson VA Medical Center, Charleston, SC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00403455
- Sponsor's protocol ID
- MHBA-009-05F
- Other IDs
- NCT00403455
- Acronym
- MTG
- Status last verified
- May 2018
- First submitted
- 22 Nov 2006
- Last updated
- 2 Jul 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Monoamine Transporters Genotypes: Risk of PTSD and Related Comorbidities
- ClinicalTrials.gov ID
- NCT00403455
- Acronym / sponsor ID
- MTG / MHBA-009-05F
- Conditions
- PTSD
- Keywords
- Clinical, Genetics, Monoamine transporter, Pharmacogenetics, Post Traumatic Stress Disorder
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- Oct 2006
- Primary completion
- Jul 2011 (actual)
- Study completion
- Jul 2011 (actual)
- First posted
- 23 Nov 2006 (estimated)
- Results
- Posted 8 Dec 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Dr. Wang's merit review is aimed at providing a better understanding of the relationship between SLC6A3/SLC6A4 and the mental health of veterans exposed to high levels of combat stress, specifically focusing on PTSD symptoms, related co-morbidities, treatment outcomes and seeks new approaches to therapy for our Veteran population.
Detailed description
Background: Post-traumatic Stress Disorder (PTSD), a debilitating condition that develops following exposure to trauma, is highly prevalent in military personnel and veterans due to high risk of trauma exposure in combat. Trauma exposure, as an environmental insult, is necessary, but itself is not sufficient to cause PTSD, since not everyone exposure to trauma develops PTSD. Brain dopamine (DAT) and serotonin (5-HTT) transporter play a critical role in the regulation of stress related psychological and behavioral functions. Genetic polymorphisms that affect 5-HTT and DAT function, such as the 5' promote polymorphism in the 5-HTT gene (SLC6A4)(5-HTTlpr) and 3' -untranslated region (UTR)-40 bp-variable number tandem repeat (VNTR)of DAT gene (SLC6A3), could influence individual susceptibility to trauma-related psychopathology.
Objective/Hypothesis: The objective of this application is to investigated the relationship between SLC6A3/SLC6A4 and the mental health of veterans exposed to high levels of combat stress, specifically focusing on PTSD symptoms, related comorbidities, and treatment outcome. The central hypothesis is that specific genetic variants that adversely affect serotonin and dopamine neurotransmission constitute a risk for the emergence of PTSD and related comorbid symptoms after trauma exposure; and, some of these variants may further influence PTSD and related response.
Specific Objectives: (1) To determine specific 5-HTTLPR genotype involvement in PTSD symptomatology, (2) to determine influence of combined SLC6A3/SLC6A4 genotypes on PTSD with substance dependence, (3)to identify 5 HTTLPR alleles that affect PTSD symptomatology and treatment outcome, and (4)to identify additional SLC6A3/SLC6A4 alleles associated with PTSD and related comorbidities.
Study Design: We have generated some preliminary data supporting our hypothesis by examining 5-HTTLPR and the 3'-UTR-VNTR of SLC6A3 genotypes in 109 combat veterans with and without PTSD. In this proposal, we will expand on these findings by recruiting 300 veterans exposed to sufficient combat stress defined by Combat Exposure Scale(CES) score of >10 and who qualify for DSM-IV category A PTSD diagnostic criteria, including approximately 150 veterans with PTSD veterans with PTSD defined using DSM-IV diagnostic criteria, Clinician Administered PTSD Scale (CAPS) score >45 and 150 healthy combat-exposed veterans as defined by a CAPS score <15. We will first apply a newly developed extreme discordant phenotype (EDP) method to examine how 5-HTTLPR and 3'-UTR-VNTR genotypes affect trauma related psychopathology in combat veterans only with the highest (>45)and lowest (<15) CAPS scores. Secondly, single nucleotide polymorphisms (SNPs)will be examined across both genes and assessed for relatedness to PTSD susceptibility or resistance. Further analyses of relationship of these polymorphisms with comorbidities will also be performed. Thirdly, a pharmacogenetic trail (using sertraline as a therapeutic agent) will be applied to assess how gene variants influence PTSD treatment outcome. To Safeguard against population stratification, a genome control method will be applied in all the genetic analyses.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Paroxetine Arm | Other | Drug: ParoxetineThis is a single arm, single site, open-label clinical trial to treat veterans with PTSD. It is a 12-week trial to investigate the efficacy of paroxetine in reducing PTSD symptoms, with the primary outcome measure using CAPS. Genetic information is included to understand why some respond and some do not respond to paroxetine treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Male and female combat veterans ages 18 years and older who meet DSM-III-R criteria for principle diagnosis of PTSD as determined by the CAP-S;
- A minimum 6-month duration of PTSD illness; 3)CGI-S score of 4 or higher and a total CAPS-2 severity score of 50 or higher at the baseline visit;
- Homozygous for either the S/S or L/L 5-HTT;
- Females must not be pregnant or lactating and must agree to an acceptable form of contraception while receiving study medication and for 1 month after.
Key exclusion criteria (10 listed)
- Presence of any other primary axis I disorder (concurrent depression will be permitted if it is judged to be secondary to development for PTSD);
- Suicide ideation or attempts within the past 3 months;
- Alcohol or substance abuse or dependence in the past six months;
- Evidence of clinically significant hepatic or renal disease;
- Previous seizure disorder or condition predisposing to seizures, or on medications that might lower the seizure threshold
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 |
|---|---|---|
| ParoxetineAlso: PaxilSSRI | Drug | Paroxetine Arm |
Primary outcome
Clinician Administered PTSD Scale (CAPS)
Time frame: 12 weeks
The CAPS assessment is used to determine the severity of an individuals PTSD. The assessment examines Re-experiencing, Avoidance and Numbing, and Hyperarousal symptoms which total score in each of these categories are added together to achieve a total CAPS score. Scores on this assessment can range from 0-136 with 0 not having any PTSD symptoms and 136 having the most symptoms possible. The study uses this assessment at the baseline and at the end of treatment to determine the decrease in this score over the course of the study.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Zhewu Wang, MD principal investigator
Ralph H. Johnson VA Medical Center, Charleston, SC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Paroxetine in people with PTSD, run by VA Office of Research and Development 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 4 inclusion and 10 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 2 Jul 2018. 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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Dec 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Clinician Administered PTSD Scale (CAPS) (time frame: 12 weeks). 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 2 Jul 2018.