Back to resultsImaging the Neuroimmune System in PTSD
Primary Purpose
Post Traumatic Stress Disorder
Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Lipopolysaccharide
Sponsored by
About this trial
This is an interventional basic science trial for Post Traumatic Stress Disorder focused on measuring Neuroimmune System, Lipopolysaccharide
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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)
Sites / Locations
- Yale University
Arms of the Study
Arm 1
Arm 2
Arm Type
No Intervention
Experimental
Arm Label
Baseline [11C]PBR28 PET Scan
Post-LPS [11C]PBR28 PET Scan
Arm Description
Subjects will complete a 120-minute baseline [11C]PBR28 PET scan.
Subjects will complete a second120-minute [11C]PBR28 PET scan 3-hours after LPS administration (1.0ng/kg; IV)
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
Baseline Visual Attention
Visual attention: response latency to identify card color (log10(ms); higher ~ worse attention).
Post-LPS Visual Attention
Visual attention: response latency to identify card color (log10(ms); higher ~ worse attention).
Baseline Visual Learning
Visual learning: % of correctly identified repeat cards (arcsine(% correct); higher values ~ better learning).
Post-LPS Visual Learning
Visual learning: % of correctly identified repeat cards (arcsine(% correct); higher values ~ better learning).
Baseline Verbal Memory
Verbal memory: # of correctly recalled items from a grocery list (3 trials). Verbal recall: # of correctly recalled items from a grocery list after a delay (1 trial; higher ~ better memory/recall).
Post-LPS Verbal Memory
Verbal memory: # of correctly recalled items from a grocery list (3 trials). Verbal recall: # of correctly recalled items from a grocery list after a delay (1 trial; higher ~ better memory/recall).
Baseline Executive Function
Executive function: number of errors navigating a 'hidden' maze (5 trials; higher ~ worse executive function).
Post-LPS Executive Function
Executive function: number of errors navigating a 'hidden' maze (5 trials; higher ~ worse executive function).
Baseline Visual-Motor Processing Speed
Visual-motor processing speed: response latency to detect a card flipped over (log10(ms); higher ~ worse processing speed).
Post-LPS Visual-Motor Processing Speed
Visual-motor processing speed: response latency to detect a card flipped over (log10(ms); higher ~ worse processing speed).
Baseline Working Memory
Working memory: % of correctly identified cards that matched the card presented either one- or two-cards previously (arcsine(% correct); higher ~ better working memory).
Post-LPS Working Memory
Working memory: % of correctly identified cards that matched the card presented either one- or two-cards previously (arcsine(% correct); higher ~ better working memory).
Baseline Social Cognition
Social cognition: response latency to identify the mismatched facial expression based on its emotional content (ms; log10; higher ~ worse social cognition).
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).
Baseline Reward Responsiveness
Reward responsiveness will be quantified via computerized Probabilistic Reward Task
Post-LPS Reward Responsiveness
Reward responsiveness will be quantified via computerized Probabilistic Reward Task
Full Information
NCT ID
NCT04236986
First Posted
January 11, 2020
Last Updated
October 23, 2023
Sponsor
Yale University
Collaborators
National Institute of Mental Health (NIMH)
1. Study Identification
Unique Protocol Identification Number
NCT04236986
Brief Title
Imaging the Neuroimmune System in PTSD
Official Title
Imaging the Neuroimmune System in PTSD With PET
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
March 28, 2017 (Actual)
Primary Completion Date
May 30, 2023 (Actual)
Study Completion Date
September 30, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Yale University
Collaborators
National Institute of Mental Health (NIMH)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief 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). 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Post Traumatic Stress Disorder
Keywords
Neuroimmune System, Lipopolysaccharide
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
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)
Allocation
Non-Randomized
Enrollment
80 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Baseline [11C]PBR28 PET Scan
Arm Type
No Intervention
Arm Description
Subjects will complete a 120-minute baseline [11C]PBR28 PET scan.
Arm Title
Post-LPS [11C]PBR28 PET Scan
Arm Type
Experimental
Arm Description
Subjects will complete a second120-minute [11C]PBR28 PET scan 3-hours after LPS administration (1.0ng/kg; IV)
Intervention Type
Drug
Intervention Name(s)
Lipopolysaccharide
Other Intervention Name(s)
LPS
Intervention Description
LPS will be administered intravenously (1.0ng/kg; IV)
Primary Outcome Measure Information:
Title
Baseline TSPO Availability
Description
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.
Time Frame
Before LPS administration (baseline)
Title
Post-LPS TSPO Availability
Description
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.
Time Frame
3-hours after LPS administration (1.0 ng/kg; IV)
Secondary Outcome Measure Information:
Title
Baseline Visual Attention
Description
Visual attention: response latency to identify card color (log10(ms); higher ~ worse attention).
Time Frame
Before LPS administration
Title
Post-LPS Visual Attention
Description
Visual attention: response latency to identify card color (log10(ms); higher ~ worse attention).
Time Frame
Approximately ~1-hour after LPS administration
Title
Baseline Visual Learning
Description
Visual learning: % of correctly identified repeat cards (arcsine(% correct); higher values ~ better learning).
Time Frame
Before LPS administration
Title
Post-LPS Visual Learning
Description
Visual learning: % of correctly identified repeat cards (arcsine(% correct); higher values ~ better learning).
Time Frame
Approximately ~1-hour after LPS administration
Title
Baseline Verbal Memory
Description
Verbal memory: # of correctly recalled items from a grocery list (3 trials). Verbal recall: # of correctly recalled items from a grocery list after a delay (1 trial; higher ~ better memory/recall).
Time Frame
Before LPS administration
Title
Post-LPS Verbal Memory
Description
Verbal memory: # of correctly recalled items from a grocery list (3 trials). Verbal recall: # of correctly recalled items from a grocery list after a delay (1 trial; higher ~ better memory/recall).
Time Frame
Approximately ~1-hour after LPS administration
Title
Baseline Executive Function
Description
Executive function: number of errors navigating a 'hidden' maze (5 trials; higher ~ worse executive function).
Time Frame
Before LPS administration
Title
Post-LPS Executive Function
Description
Executive function: number of errors navigating a 'hidden' maze (5 trials; higher ~ worse executive function).
Time Frame
Approximately ~1-hour after LPS administration
Title
Baseline Visual-Motor Processing Speed
Description
Visual-motor processing speed: response latency to detect a card flipped over (log10(ms); higher ~ worse processing speed).
Time Frame
Before LPS administration
Title
Post-LPS Visual-Motor Processing Speed
Description
Visual-motor processing speed: response latency to detect a card flipped over (log10(ms); higher ~ worse processing speed).
Time Frame
Approximately ~1-hour after LPS administration
Title
Baseline Working Memory
Description
Working memory: % of correctly identified cards that matched the card presented either one- or two-cards previously (arcsine(% correct); higher ~ better working memory).
Time Frame
Before LPS administration
Title
Post-LPS Working Memory
Description
Working memory: % of correctly identified cards that matched the card presented either one- or two-cards previously (arcsine(% correct); higher ~ better working memory).
Time Frame
Approximately ~1-hour after LPS administration
Title
Baseline Social Cognition
Description
Social cognition: response latency to identify the mismatched facial expression based on its emotional content (ms; log10; higher ~ worse social cognition).
Time Frame
Before LPS administration
Title
Post-LPS Social Cognition
Description
Social cognition: response latency to identify the mismatched facial expression based on its emotional content (ms; log10; higher ~ worse social cognition).
Time Frame
Approximately ~1-hour after LPS administration
Title
Baseline Reward Responsiveness
Description
Reward responsiveness will be quantified via computerized Probabilistic Reward Task
Time Frame
Before LPS administration
Title
Post-LPS Reward Responsiveness
Description
Reward responsiveness will be quantified via computerized Probabilistic Reward Task
Time Frame
Approximately ~2-hour after LPS administration
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kelly Cosgrove, PhD
Organizational Affiliation
Yale University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Yale University
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06519
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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Imaging the Neuroimmune System in PTSD
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