Posttraumatic Stress DisorderEarly Phase 1K01NCT03048929
Inflammation and Threat Sensitivity in PTSD
A Early Phase 1 study testing Typhoid Vi Polysaccharide Vaccine in people with Posttraumatic Stress Disorder, run by University of California, San Francisco at 2 sites in United States.
Trial summary
The overall goals of this study are to examine the relationship between chronic inflammation and threat and reward sensitivity, and to determine the effects of acute inflammation on threat sensitivity, in individuals with and without moderate to severe PTSD symptoms. Read more about this study
- Who is it for?
- Ages 30 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Posttraumatic Stress Disorder
- What is being tested?
- Typhoid Vi Polysaccharide Vaccine
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Apr 2019to 31 Mar 2021
- Phase
- Early Phase 1
- 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 30 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- All Subjects:
- Veterans aged 30-60.
- PTSD Subjects:
- Positive for current chronic moderate to severe PTSD symptoms of at least three months duration as indexed by the Clinically Administered PTSD Scale for DSM 5 (CAPS-5).
- Control Subjects:
- Negative for lifetime PTSD.
- Negative for lifetime diagnosis of Mood Disorders, Generalized Anxiety Disorder, Obsessive-Compulsive Disorder and Panic Disorder.
Who cannot join
- All Subjects:
- Lifetime history of any psychiatric disorder with psychotic features, bipolar disorder, panic disorder, obsessive-compulsive disorder, alcohol or substance dependence, or a history of alcohol or substance abuse within the past 2 years.
- Currently exposed to recurrent trauma or have been exposed to a traumatic event within the past 3 months.
- Diagnosis of neurologic disorder, systemic illness affecting central nervous system function, and/or anemia.
- Prominent suicidal or homicidal ideation.
- Current and planned ongoing use of medications that impact inflammation or immune function, or use of such medications in the past 6 months.
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- Subjects currently receiving serotonin reuptake inhibitors (SSRIs), benzodiazepine or benzodiazepine receptor agonists, anticonvulsants, atypical antipsychotic medication, any antidepressant medication including trazodone.
- Termination of SSRIs, benzodiazepine or benzodiazepine receptor agonists, anticonvulsants, atypical antipsychotic medication, any antidepressant medication including trazodone in the last month or plans to start these medications during the course of the study.
- Contraindications to Magnetic Resonance Imaging (MRI), which include claustrophobia severe enough to prevent MRI examination and presence of ferrometallic objects in the body that would interfere with MR examination and/or cause a safety risk (e.g., pace makers, implanted stimulators, pumps).
- Contraindications to typhoid vaccine, which include acute febrile illness within the past two weeks, disorders characterized by a deficiency in ability to mount a humoral or cell-mediated immune response, use of anti-malarial medications in past six months, antibiotics in past three months, a history of hypersensitivity to typhoid vaccine or any other vaccine, previous immunization with whole-cell typhoid or live, oral typhoid vaccine, vaccination with the polysaccharide version of the typhoid vaccine within the past 3 year, coagulation disorders and thrombocytopenia.
- Conditions or use of substances that may be associated with inflammation independent of trauma and PTSD, including chronic physical disease.
- History of neurologic disorders, traumatic brain injury (TBI), brain tumor, brain hemorrhage, or head injury with loss of consciousness.
- Women who are currently, or are planning to become, pregnant during the study.
- The investigators will not exclude PTSD patients who are receiving psychotherapy, but will apply the following criteria: patients must have been in treatment for 6 months, meet symptomatic criteria for inclusion, and do not have plans to discontinue treatment during the course of the study.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
San Francisco Veterans Affairs Medical Center
San Francisco, California, 94121
University of California, San Francisco
San Francisco, California, 94143
About this study
Official title: Effects of Inflammation on Neural Mechanisms of Threat Sensitivity in Posttraumatic Stress Disorder
The overall goals of this study are to examine the relationship between chronic inflammation and threat and reward sensitivity, and to determine the effects of acute inflammation on threat sensitivity, in individuals with and without moderate to severe PTSD symptoms. The investigators will first conduct an observational study to examine the relationship between chronic inflammation and neural and behavioral measures of threat sensitivity. Then, the investigators will conduct a randomized, double-blind, placebo-controlled, between-subjects study to examine the effects of acute inflammation on neural and behavioral measures of threat sensitivity.
Read the detailed description
Posttraumatic stress disorder (PTSD) is a disabling chronic psychiatric disorder that affects more than 8% of the population. New treatments for PTSD symptoms are desperately needed because current pharmacologic and behavioral treatments for PTSD are inadequate or they have low uptake. Accumulating evidence supports elevated inflammation as a new potential treatment target for PTSD. Inflammation is increased in PTSD, and can promote threat sensitivity, a core mechanism underlying several PTSD symptoms. Two major gaps in knowledge prevent progress towards effective anti- inflammatory treatments for PTSD symptoms. First, researchers know little about the relationship between chronic inflammation and exaggerated threat sensitivity. Second, no studies have directly examined the effects of acute inflammation on neural and behavioral measures of threat sensitivity in PTSD. The objective of this study is to uncover the effects of chronic and acute inflammation on neural mechanisms and behavioral measures of threat sensitivity in individuals with and without PTSD symptoms. The central hypothesis is that both chronic and acute inflammation will be associated with exaggerated threat sensitivity overall, with particularly strong relationships in PTSD. The scientific rationale is that establishing a link between elevated inflammation and threat sensitivity in both observational and experimental studies in individuals with and without PTSD symptoms will drive progress towards a targeted approach to identifying effective anti- inflammatory treatments for PTSD symptoms. In particular, this work has the potential to identify a target for clinical trials of anti-inflammatory interventions in PTSD. Guided by preliminary data, hypotheses will be tested by pursuing two specific aims: 1) Examine the association of chronic inflammation with threat sensitivity; and 2) Determine the effects of an acute inflammatory challenge on threat sensitivity. To achieve these aims, 40 participants with moderate to severe PTSD symptoms and 40 age- and body mass index-matched trauma-exposed participants with no history of PTSD will be recruited. The investigators will assess chronic resting levels of inflammation (Aim 1) and will randomize participants to placebo or inflammatory challenge using polysaccharide typhoid vaccine (i.e., endotoxin) (Aim 2) and will use validated functional MRI paradigms and behavioral tasks to assess threat sensitivity.
- Conditions
- Posttraumatic Stress Disorder
- Being tested
- Typhoid Vi Polysaccharide Vaccine, 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.
Typhoid Vi Polysaccharide VaccineBiological
Salmonella typhi capsular polysaccharide vaccine (Typhoid Vi Polysaccharide Vaccine): Each dose of 0.5ml Salmonella typhi capsular polysaccharide vaccine (Sanofi Pasteur, SA) is formulated to contain 25μg of purified Vi polysaccharide in a colorless isotonic phosphate buffered saline (pH 7±0.3), 4.150mg of sodium chloride, 0.065mg of disodium phosphate, 0.023mg of monosodium phosphate and 0.5ml of sterile water for injection. It is indicated for use by humans aged 2 years and older for protection against typhoid fever.
PlaceboBiological
The placebo injection will consist of 0.5mL of saline.
| Study group | Role | What they receive |
|---|---|---|
| Typhoid Vi Polysaccharide Vaccine | Active comparator | Patients will receive one intramuscular 0.5 mL injection of Typhoid Vi Polysaccharide Vaccine containing 0.025 mg purified Vi polysaccharide. Receives: Biological: Typhoid Vi Polysaccharide Vaccine |
| Placebo | Placebo comparator | Patients will receive one intramuscular 0.5 mL injection of saline placebo. Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Neural activity to threat as assessed with functional magnetic resonance imaging
On visits 1 (baseline) and 2 (post-vaccine or post-placebo administration), participants will perform computerized threat and reward tasks and investigators will measure and compare neural activity between groups (PTSD vs. control) and condition (endotoxin vs. placebo).
Measured: Change from Visit 1 (baseline) to Visit 2 (within two weeks of baseline)
Secondary outcomes (1)
Threat sensitivity
Participants will perform computerized tasks designed to assess threat sensitivity.
Measured: Change from Visit 1 (baseline) to Visit 2 (within two weeks of baseline)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2017 (estimated)
- Study start1 Apr 2019
- Primary completion30 Mar 2020
- Study completion31 Mar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Posttraumatic Stress DisorderStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe 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
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor
- Investigators
- Aoife S O'Donovan, PhD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03048929
- Sponsor's protocol ID
- 15-18367
- Other IDs
- K01MH109871
- Acronym
- K01
- Status last verified
- May 2021
- First submitted
- 2 Feb 2017
- Last updated
- 13 May 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Inflammation on Neural Mechanisms of Threat Sensitivity in Posttraumatic Stress Disorder
- ClinicalTrials.gov ID
- NCT03048929
- Acronym / sponsor ID
- K01 / 15-18367
- Conditions
- Posttraumatic Stress Disorder
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 1 Apr 2019 (actual)
- Primary completion
- 30 Mar 2020 (actual)
- Study completion
- 31 Mar 2021 (actual)
- First posted
- 9 Feb 2017 (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.
The overall goals of this study are to examine the relationship between chronic inflammation and threat and reward sensitivity, and to determine the effects of acute inflammation on threat sensitivity, in individuals with and without moderate to severe PTSD symptoms. The investigators will first conduct an observational study to examine the relationship between chronic inflammation and neural and behavioral measures of threat sensitivity. Then, the investigators will conduct a randomized, double-blind, placebo-controlled, between-subjects study to examine the effects of acute inflammation on neural and behavioral measures of threat sensitivity.
Detailed description
Posttraumatic stress disorder (PTSD) is a disabling chronic psychiatric disorder that affects more than 8% of the population. New treatments for PTSD symptoms are desperately needed because current pharmacologic and behavioral treatments for PTSD are inadequate or they have low uptake. Accumulating evidence supports elevated inflammation as a new potential treatment target for PTSD. Inflammation is increased in PTSD, and can promote threat sensitivity, a core mechanism underlying several PTSD symptoms. Two major gaps in knowledge prevent progress towards effective anti- inflammatory treatments for PTSD symptoms. First, researchers know little about the relationship between chronic inflammation and exaggerated threat sensitivity. Second, no studies have directly examined the effects of acute inflammation on neural and behavioral measures of threat sensitivity in PTSD. The objective of this study is to uncover the effects of chronic and acute inflammation on neural mechanisms and behavioral measures of threat sensitivity in individuals with and without PTSD symptoms. The central hypothesis is that both chronic and acute inflammation will be associated with exaggerated threat sensitivity overall, with particularly strong relationships in PTSD. The scientific rationale is that establishing a link between elevated inflammation and threat sensitivity in both observational and experimental studies in individuals with and without PTSD symptoms will drive progress towards a targeted approach to identifying effective anti- inflammatory treatments for PTSD symptoms. In particular, this work has the potential to identify a target for clinical trials of anti-inflammatory interventions in PTSD. Guided by preliminary data, hypotheses will be tested by pursuing two specific aims: 1) Examine the association of chronic inflammation with threat sensitivity; and 2) Determine the effects of an acute inflammatory challenge on threat sensitivity. To achieve these aims, 40 participants with moderate to severe PTSD symptoms and 40 age- and body mass index-matched trauma-exposed participants with no history of PTSD will be recruited. The investigators will assess chronic resting levels of inflammation (Aim 1) and will randomize participants to placebo or inflammatory challenge using polysaccharide typhoid vaccine (i.e., endotoxin) (Aim 2) and will use validated functional MRI paradigms and behavioral tasks to assess threat sensitivity.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Typhoid Vi Polysaccharide Vaccine | Active comparator | Biological: Typhoid Vi Polysaccharide VaccinePatients will receive one intramuscular 0.5 mL injection of Typhoid Vi Polysaccharide Vaccine containing 0.025 mg purified Vi polysaccharide. |
| Placebo | Placebo comparator | Biological: PlaceboPatients will receive one intramuscular 0.5 mL injection of saline placebo. |
Who may qualify
- Ages
- 30 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Veterans aged 30-60.
- Positive for current chronic moderate to severe PTSD symptoms of at least three months duration as indexed by the Clinically Administered PTSD Scale for DSM 5 (CAPS-5).
- Negative for lifetime PTSD.
- Negative for lifetime diagnosis of Mood Disorders, Generalized Anxiety Disorder, Obsessive-Compulsive Disorder and Panic Disorder.
Key exclusion criteria (14 listed)
- Lifetime history of any psychiatric disorder with psychotic features, bipolar disorder, panic disorder, obsessive-compulsive disorder, alcohol or substance dependence, or a history of alcohol or substance abuse within the past 2 years.
- Currently exposed to recurrent trauma or have been exposed to a traumatic event within the past 3 months.
- Diagnosis of neurologic disorder, systemic illness affecting central nervous system function, and/or anemia.
- Prominent suicidal or homicidal ideation.
- Current and planned ongoing use of medications that impact inflammation or immune function, or use of such medications in the past 6 months.
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 |
|---|---|---|
| Typhoid Vi Polysaccharide VaccineSalmonella typhi capsular polysaccharide vaccine (Typhoid Vi Polysaccharide Vaccine): Each dose of 0.5ml Salmonella typhi capsular polysaccharide vaccine (Sanofi Pasteur, SA) is formulated to contain 25μg of purified Vi polysaccharide in a colorless isotonic phosphate buffered saline (pH 7±0.3), 4.150mg of sodium chloride, 0.065mg of disodium phosphate, 0.023mg of monosodium phosphate and 0.5ml of sterile water for injection. It is indicated for use by humans aged 2 years and older for protection against typhoid fever. | Biological | Typhoid Vi Polysaccharide Vaccine |
| PlaceboThe placebo injection will consist of 0.5mL of saline. | Biological | Placebo |
Primary outcome
Neural activity to threat as assessed with functional magnetic resonance imaging
Time frame: Change from Visit 1 (baseline) to Visit 2 (within two weeks of baseline)
On visits 1 (baseline) and 2 (post-vaccine or post-placebo administration), participants will perform computerized threat and reward tasks and investigators will measure and compare neural activity between groups (PTSD vs. control) and condition (endotoxin vs. placebo).
1 secondary outcome
Threat sensitivity
Time frame: Change from Visit 1 (baseline) to Visit 2 (within two weeks of baseline)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2021.
- Individual participant dataSharing planned: No
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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.
Aoife S O'Donovan, PhD principal investigator
University of California, San Francisco
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Typhoid Vi Polysaccharide Vaccine in people with Posttraumatic Stress Disorder, run by University of California, San Francisco at 2 sites 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 7 inclusion and 14 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 13 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Neural activity to threat as assessed with functional magnetic resonance imaging (time frame: Change from Visit 1 (baseline) to Visit 2 (within two weeks of baseline)). 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 13 May 2021.