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Completed

NCT Number: NCT04236986

Imaging the Neuroimmune System in PTSD

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.

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Key information

Conditions

Post Traumatic Stress Disorder Mental Disorders Stress Disorders, Post-Traumatic Stress Disorders, Traumatic Trauma and Stressor Related Disorders

Age range

18 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Yale University

New Haven, Connecticut, 06519, United States

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

lipopolysaccharide

Drug

LPS will be administered intravenously (1.0ng/kg; IV)

Other names: LPS

Primary outcomes

  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 outcomes

  1. Baseline Visual Attention

    Time frame: Before LPS administration

    Visual attention: response latency to identify card color (log10(ms); higher ~ worse attention).

  2. Post-LPS Visual Attention

    Time frame: Approximately ~1-hour after LPS administration

    Visual attention: response latency to identify card color (log10(ms); higher ~ worse attention).

  3. Baseline Visual Learning

    Time frame: Before LPS administration

    Visual learning: % of correctly identified repeat cards (arcsine(% correct); higher values ~ better learning).

  4. Post-LPS Visual Learning

    Time frame: Approximately ~1-hour after LPS administration

    Visual learning: % of correctly identified repeat cards (arcsine(% correct); higher values ~ better learning).

  5. Baseline Verbal Memory

    Time frame: Before LPS administration

    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.

  6. Post-LPS Verbal Memory

    Time frame: Approximately ~1-hour after LPS administration

    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.

  7. Baseline Executive Function

    Time frame: Before LPS administration

    Executive function: summed number of errors navigating a 'hidden' maze (5 trials; higher ~ worse executive function).

  8. Post-LPS Executive Function

    Time frame: Approximately ~1-hour after LPS administration

    Executive function: summed number of errors navigating a 'hidden' maze (5 trials; higher ~ worse executive function).

  9. Baseline Visual-Motor Processing Speed

    Time frame: Before LPS administration

    Visual-motor processing speed: response latency to detect a card flipped over (log10(ms); higher ~ worse processing speed).

  10. Post-LPS Visual-Motor Processing Speed

    Time frame: Approximately ~1-hour after LPS administration

    Visual-motor processing speed: response latency to detect a card flipped over (log10(ms); higher ~ worse processing speed).

  11. Baseline Social Cognition

    Time frame: Before LPS administration

    Social cognition: response latency to identify the mismatched facial expression based on its emotional content (ms; log10; higher ~ worse social cognition).

  12. Post-LPS Social Cognition

    Time frame: Approximately ~1-hour after LPS administration

    Social cognition: response latency to identify the mismatched facial expression based on its emotional content (ms; log10; higher ~ worse social cognition).

Sponsors and collaborators

Lead sponsor

Yale University

Other

Collaborators

  • National Institute of Mental Health (NIMH)

Registry information

Official study title

Imaging the Neuroimmune System in PTSD With PET

Important dates

Study start
2017
Primary completion
2023
Study completion
2023
First posted
Jan 22, 2020
Registry last updated
Dec 9, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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