Post Traumatic Stress DisorderPhase 1NCT04236986
Imaging the Neuroimmune System in PTSD
A Phase 1 study testing Lipopolysaccharide in people with Post Traumatic Stress Disorder, run by Yale University at 1 site in United States.
Trial summary
In this study, individuals with and without post-traumatic stress disorder (PTSD) will undergo one positron emission tomography (PET) scan using the radiotracer [11C]PBR28, which binds to the 18kDa translocator protein (TSPO). Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Post Traumatic Stress Disorder
- What is being tested?
- Lipopolysaccharide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Mar 2017to 30 May 2023
- Phase
- Phase 1
- 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 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Men and women, aged 18-55 years
- Subjects with PTSD will have a primary, current diagnosis of PTSD according to DSM-V criteria (i.e., CAPS-5 ascertained diagnosis)
- Able to read and write English and to provide voluntary, written informed consent
Who cannot join
- Current medical condition such as neurological, cardiovascular, endocrine, renal, liver, or thyroid pathology including COPD, anemia, uncontrolled daily asthma or asthma requiring the use of an inhaler more than 1x/week with an ACT score below 20. [We will not exclude individuals taking SSRIs and TRIs due to high prevalence of use within the PTSD population and due to evidence suggesting no effect of these drug classes on endotoxin response].
- Past or current neurological disorder or disorders affecting the brain including but not limited to multiple sclerosis, history of stroke, brain tumors, traumatic brain injury with loss of consciousness, seizure disorder
- Current or regular use of over-the-counter medication that may affect the immune system
- Women who are pregnant or nursing, or fail to use one of the following methods of birth control unless she or partner is surgically sterile or she is postmenopausal (hormone contraceptives [oral, implant, injection, patch, or ring], contraceptive sponge, double barrier [diaphragm or condom plus spermicide], or IUD
- Contraindications to MRI such as claustrophobia or metal in their body
- Individuals who are classified as "low binders" for the rs6971 polymorphism (<10% of the population)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Imaging the Neuroimmune System in PTSD With PET
In this study, individuals with and without post-traumatic stress disorder (PTSD) will undergo one positron emission tomography (PET) scan using the radiotracer [11C]PBR28, which binds to the 18kDa translocator protein (TSPO). A subset of individuals who complete the first PET [11C]PBR28 scan will be invited to complete an inflammatory challenge and second PET [11C]PBR28 scan. Approximately 3 hours prior to the second [11C]PBR28 PET scan, lipopolysaccharide (LPS; endotoxin) will be administered to evoke a robust neuroimmune response. Subjects will also undergo behavioral and cognitive testing. Vital signs, subjective response, and peripheral biomarker levels will be assayed periodically throughout the experimental session.
Specific aims: 1) Determine if individuals with PTSD exhibit neuroimmune system disruption relative to well-matched comparators at baseline. 2) Determine if individuals with PTSD exhibit a disrupted neuroimmune response after a classical immune stimulus relative to well-matched comparators. 3) Determine if LPS differentially alters cognitive function, subjective response, or physiological markers in individuals with PTSD compared to well-matched comparators.
Hypothesis: Individuals with PTSD will exhibit a suppressed neuroimmune system at baseline and an attenuated neuroimmune response following LPS challenge, relative to matched trauma controls.
- Conditions
- Post Traumatic Stress Disorder
- Being tested
- Lipopolysaccharide
- Keywords
- Neuroimmune System, Lipopolysaccharide
- 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.
LipopolysaccharideDrug
Also called LPS
LPS will be administered intravenously (1.0ng/kg; IV)
| Study group | Role | What they receive |
|---|---|---|
| Baseline [11C]PBR28 PET Scan | No intervention | Subjects will complete a 120-minute baseline [11C]PBR28 PET scan. |
| Post-LPS [11C]PBR28 PET Scan | Experimental | Subjects will complete a second120-minute [11C]PBR28 PET scan 3-hours after LPS administration (1.0ng/kg; IV) Receives: Drug: Lipopolysaccharide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Baseline TSPO Availability
Time-activity curves will be extracted from brain regions of interest and analyzed using multilinear analysis-1 (t*=30) incorporating the metabolite-corrected arterial input function to yield [11C]PBR28 total volumes of distribution (VT) across brain regions.
Measured: Before LPS administration (baseline)
Post-LPS TSPO Availability
Time-activity curves will be extracted from brain regions of interest and analyzed using multilinear analysis-1 (t*=30) incorporating the metabolite-corrected arterial input function to yield [11C]PBR28 total volumes of distribution (VT) across brain regions.
Measured: 3-hours after LPS administration (1.0 ng/kg; IV)
Secondary outcomes (12)
Baseline Visual Attention
Visual attention: response latency to identify card color (log10(ms); higher ~ worse attention).
Measured: Before LPS administration
Post-LPS Visual Attention
Visual attention: response latency to identify card color (log10(ms); higher ~ worse attention).
Measured: Approximately ~1-hour after LPS administration
Baseline Visual Learning
Visual learning: % of correctly identified repeat cards (arcsine(% correct); higher values ~ better learning).
Measured: Before LPS administration
Post-LPS Visual Learning
Visual learning: % of correctly identified repeat cards (arcsine(% correct); higher values ~ better learning).
Measured: Approximately ~1-hour after LPS administration
Baseline Verbal Memory
Verbal memory: summed number of correctly recalled items from a grocery list (over 3 trials). Each trial is not calculated individually. The reported value is the sum of all three trials.
Measured: Before LPS administration
Post-LPS Verbal Memory
Verbal memory: summed # of correctly recalled items from a grocery list (over 3 trials). Each trial is not calculated individually. The reported value is the sum of all three trials.
Measured: Approximately ~1-hour after LPS administration
Baseline Executive Function
Executive function: summed number of errors navigating a 'hidden' maze (5 trials; higher ~ worse executive function).
Measured: Before LPS administration
Post-LPS Executive Function
Executive function: summed number of errors navigating a 'hidden' maze (5 trials; higher ~ worse executive function).
Measured: Approximately ~1-hour after LPS administration
Baseline Visual-Motor Processing Speed
Visual-motor processing speed: response latency to detect a card flipped over (log10(ms); higher ~ worse processing speed).
Measured: Before LPS administration
Post-LPS Visual-Motor Processing Speed
Visual-motor processing speed: response latency to detect a card flipped over (log10(ms); higher ~ worse processing speed).
Measured: Approximately ~1-hour after LPS administration
Baseline Social Cognition
Social cognition: response latency to identify the mismatched facial expression based on its emotional content (ms; log10; higher ~ worse social cognition).
Measured: Before LPS administration
Post-LPS Social Cognition
Social cognition: response latency to identify the mismatched facial expression based on its emotional content (ms; log10; higher ~ worse social cognition).
Measured: Approximately ~1-hour after LPS administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2020
- Study start28 Mar 2017
- Primary completion30 May 2023
- Study completion30 May 2023
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 Post Traumatic Stress DisorderStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe 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 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- All subjects will complete a baseline PET \[11C\]PBR28 scan. A subset of subjects will complete a second PET \[11C\]PBR28 scan 3-hours after systemic LPS challenge (1.0 ng/kg; IV).
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Kelly Cosgrove, Yale University
- Investigators
- Kelly Cosgrove, PhD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04236986
- Sponsor's protocol ID
- 2000020347
- Other IDs
- 1R01MH110674-01A1
- Status last verified
- Nov 2024
- First submitted
- 11 Jan 2020
- Last updated
- 9 Dec 2024
- Results posted
- Yes, on ClinicalTrials.gov
- 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 9 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Imaging the Neuroimmune System in PTSD With PET
- ClinicalTrials.gov ID
- NCT04236986
- Acronym / sponsor ID
- 2000020347
- Conditions
- Post Traumatic Stress Disorder
- Keywords
- Neuroimmune System, Lipopolysaccharide
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 28 Mar 2017 (actual)
- Primary completion
- 30 May 2023 (actual)
- Study completion
- 30 May 2023 (actual)
- First posted
- 22 Jan 2020 (actual)
- Results
- Posted 26 Sep 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In this study, individuals with and without post-traumatic stress disorder (PTSD) will undergo one positron emission tomography (PET) scan using the radiotracer [11C]PBR28, which binds to the 18kDa translocator protein (TSPO). A subset of individuals who complete the first PET [11C]PBR28 scan will be invited to complete an inflammatory challenge and second PET [11C]PBR28 scan. Approximately 3 hours prior to the second [11C]PBR28 PET scan, lipopolysaccharide (LPS; endotoxin) will be administered to evoke a robust neuroimmune response. Subjects will also undergo behavioral and cognitive testing. Vital signs, subjective response, and peripheral biomarker levels will be assayed periodically throughout the experimental session.
Specific aims: 1) Determine if individuals with PTSD exhibit neuroimmune system disruption relative to well-matched comparators at baseline. 2) Determine if individuals with PTSD exhibit a disrupted neuroimmune response after a classical immune stimulus relative to well-matched comparators. 3) Determine if LPS differentially alters cognitive function, subjective response, or physiological markers in individuals with PTSD compared to well-matched comparators.
Hypothesis: Individuals with PTSD will exhibit a suppressed neuroimmune system at baseline and an attenuated neuroimmune response following LPS challenge, relative to matched trauma controls.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- All subjects will complete a baseline PET [11C]PBR28 scan. A subset of subjects will complete a second PET [11C]PBR28 scan 3-hours after systemic LPS challenge (1.0 ng/kg; IV).
| Arm | Type | Receives |
|---|---|---|
| Baseline [11C]PBR28 PET Scan | No intervention | –Subjects will complete a 120-minute baseline [11C]PBR28 PET scan. |
| Post-LPS [11C]PBR28 PET Scan | Experimental | Drug: LipopolysaccharideSubjects will complete a second120-minute [11C]PBR28 PET scan 3-hours after LPS administration (1.0ng/kg; IV) |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Men and women, aged 18-55 years
- Subjects with PTSD will have a primary, current diagnosis of PTSD according to DSM-V criteria (i.e., CAPS-5 ascertained diagnosis)
- Able to read and write English and to provide voluntary, written informed consent
Key exclusion criteria (6 listed)
- Current medical condition such as neurological, cardiovascular, endocrine, renal, liver, or thyroid pathology including COPD, anemia, uncontrolled daily asthma or asthma requiring the use of an inhaler more than 1x/week with an ACT score below 20. [We will not exclude individuals taking SSRIs and TRIs due to high prevalence of use within the PTSD population and due to evidence suggesting no effect of these drug classes on endotoxin response].
- Past or current neurological disorder or disorders affecting the brain including but not limited to multiple sclerosis, history of stroke, brain tumors, traumatic brain injury with loss of consciousness, seizure disorder
- Current or regular use of over-the-counter medication that may affect the immune system
- Women who are pregnant or nursing, or fail to use one of the following methods of birth control unless she or partner is surgically sterile or she is postmenopausal (hormone contraceptives [oral, implant, injection, patch, or ring], contraceptive sponge, double barrier [diaphragm or condom plus spermicide], or IUD
- Contraindications to MRI such as claustrophobia or metal in their body
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 |
|---|---|---|
| LipopolysaccharideAlso: LPSLPS will be administered intravenously (1.0ng/kg; IV) | Drug | Post-LPS [11C]PBR28 PET Scan |
Primary outcome
Baseline TSPO Availability
Time frame: Before LPS administration (baseline)
Time-activity curves will be extracted from brain regions of interest and analyzed using multilinear analysis-1 (t*=30) incorporating the metabolite-corrected arterial input function to yield [11C]PBR28 total volumes of distribution (VT) across brain regions.
Post-LPS TSPO Availability
Time frame: 3-hours after LPS administration (1.0 ng/kg; IV)
Time-activity curves will be extracted from brain regions of interest and analyzed using multilinear analysis-1 (t*=30) incorporating the metabolite-corrected arterial input function to yield [11C]PBR28 total volumes of distribution (VT) across brain regions.
12 secondary outcomes
Baseline Visual Attention
Time frame: Before LPS administration
Post-LPS Visual Attention
Time frame: Approximately ~1-hour after LPS administration
Baseline Visual Learning
Time frame: Before LPS administration
Post-LPS Visual Learning
Time frame: Approximately ~1-hour after LPS administration
Baseline Verbal Memory
Time frame: Before LPS administration
Post-LPS Verbal Memory
Time frame: Approximately ~1-hour after LPS administration
Baseline Executive Function
Time frame: Before LPS administration
Post-LPS Executive Function
Time frame: Approximately ~1-hour after LPS administration
Baseline Visual-Motor Processing Speed
Time frame: Before LPS administration
Post-LPS Visual-Motor Processing Speed
Time frame: Approximately ~1-hour after LPS administration
Baseline Social Cognition
Time frame: Before LPS administration
Post-LPS Social Cognition
Time frame: Approximately ~1-hour after LPS administration
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Dec 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
Kelly Cosgrove, PhD principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Lipopolysaccharide in people with Post Traumatic Stress Disorder, run by Yale University 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 3 inclusion and 6 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 9 Dec 2024. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 26 Sep 2024). 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?
Baseline TSPO Availability (time frame: Before LPS administration (baseline)). The study lists 2 primary outcomes in all. 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 9 Dec 2024.