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Neuroimmune System in PTSD

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ClinicalTrials.gov Identifier: NCT04236986
Recruitment Status : Recruiting
First Posted : January 22, 2020
Last Update Posted : January 22, 2020
Sponsor:
Information provided by (Responsible Party):
Kelly Cosgrove, Yale University

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.


Condition or disease Intervention/treatment Phase
Post Traumatic Stress Disorder Drug: Lipopolysaccharide Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention 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)
Primary Purpose: Basic Science
Official Title: Imaging the Neuroimmune System in PTSD With PET
Actual Study Start Date : March 28, 2017
Estimated Primary Completion Date : April 30, 2022
Estimated Study Completion Date : April 30, 2022

Arm Intervention/treatment
No Intervention: Baseline [11C]PBR28 PET Scan
Subjects will complete a 120-minute baseline [11C]PBR28 PET scan.
Experimental: Post-LPS [11C]PBR28 PET Scan
Subjects will complete a second120-minute [11C]PBR28 PET scan 3-hours after LPS administration (1.0ng/kg; IV)
Drug: Lipopolysaccharide
LPS will be administered intravenously (1.0ng/kg; IV)
Other Name: LPS




Primary Outcome Measures :
  1. 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.

  2. 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.


Secondary Outcome Measures :
  1. Baseline Cogstate Cognitive Battery performance [ Time Frame: Before LPS administration ]
    Visual attention: response latency to identify card color (log10(ms); higher ~ worse attention). Visual learning: % of correctly identified repeat cards (arcsine(% correct); higher values ~ better learning). 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). Executive function: number of errors navigating a 'hidden' maze (5 trials; higher ~ worse executive function). Visual-motor processing speed: response latency to detect a card flipped over (log10(ms); higher ~ worse processing speed). Working memory: % of correctly identified cards that matched the card presented either one- or two-cards previously (arcsine(% correct); higher ~ better working memory). Social cognition: response latency to identify the mismatched facial expression based on its emotional content (ms; log10; higher ~ worse social cognition).

  2. Post-LPS Cogstate Cognitive Battery performance [ Time Frame: Approximately 1-hour after LPS administration ]
    Visual attention: response latency to identify card color (log10(ms); higher ~ worse attention). Visual learning: % of correctly identified repeat cards (arcsine(% correct); higher values ~ better learning). 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). Executive function: number of errors navigating a 'hidden' maze (5 trials; higher ~ worse executive function). Visual-motor processing speed: response latency to detect a card flipped over (log10(ms); higher ~ worse processing speed). Working memory: % of correctly identified cards that matched the card presented either one- or two-cards previously (arcsine(% correct); higher ~ better working memory). Social cognition: response latency to identify the mismatched facial expression based on its emotional content (ms; log10; higher ~ worse social cognition).



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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Men and women, aged 18-55 years
  2. Subjects with PTSD will have a primary, current diagnosis of PTSD according to DSM-V criteria (i.e., CAPS-5 ascertained diagnosis)
  3. Able to read and write English and to provide voluntary, written informed consent

Exclusion Criteria:

  1. 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.
  2. 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
  3. Current or regular use of over-the-counter medication that may affect the immune system
  4. 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
  5. Contraindications to MRI such as claustrophobia or metal in their body
  6. Individuals who are classified as "low binders" for the rs6971 polymorphism (<10% of the population)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04236986


Contacts
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Contact: Jon Anderson 2037377074 jonmikael.anderson@yale.edu

Locations
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United States, Connecticut
Yale University Recruiting
New Haven, Connecticut, United States, 06519
Contact: Jon Anderson    203-737-7074    jonmikael.anderson@yale.edu   
Principal Investigator: Kelly Cosgrove, PhD         
Sponsors and Collaborators
Yale University
Investigators
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Principal Investigator: Kelly Cosgrove, PhD Yale University
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Responsible Party: Kelly Cosgrove, Associate Professor, Yale University
ClinicalTrials.gov Identifier: NCT04236986    
Other Study ID Numbers: 2000020347
First Posted: January 22, 2020    Key Record Dates
Last Update Posted: January 22, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Kelly Cosgrove, Yale University:
Neuroimmune System
Lipopolysaccharide
Additional relevant MeSH terms:
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Stress Disorders, Traumatic
Stress Disorders, Post-Traumatic
Trauma and Stressor Related Disorders
Mental Disorders