Imaging the Neuroimmune System in PTSD

Post Traumatic Stress Disorder Clinical Trial

Official title:

Imaging the Neuroimmune System in PTSD With PET

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04236986
• Other study ID #: 2000020347
• Secondary ID: 1R01MH110674-01A
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: March 28, 2017
• Est. completion date: September 30, 2024

Study information

• Verified date: October 2023
• Source: Yale University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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). 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 80
• Est. completion date: September 30, 2024
• Est. primary completion date: May 30, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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. [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].

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)

Related Conditions & MeSH terms

• Post Traumatic Stress Disorder
• Stress Disorders, Post-Traumatic
• Stress Disorders, Traumatic

Intervention

Drug:
• Lipopolysaccharide
LPS will be administered intravenously (1.0ng/kg; IV)

Locations

Country	Name	City	State
United States	Yale University	New Haven	Connecticut

Sponsors (2)

Lead Sponsor	Collaborator
Yale University	National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Before LPS administration (baseline)
Primary	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.	3-hours after LPS administration (1.0 ng/kg; IV)
Secondary	Baseline Visual Attention	Visual attention: response latency to identify card color (log10(ms); higher ~ worse attention).	Before LPS administration
Secondary	Post-LPS Visual Attention	Visual attention: response latency to identify card color (log10(ms); higher ~ worse attention).	Approximately ~1-hour after LPS administration
Secondary	Baseline Visual Learning	Visual learning: % of correctly identified repeat cards (arcsine(% correct); higher values ~ better learning).	Before LPS administration
Secondary	Post-LPS Visual Learning	Visual learning: % of correctly identified repeat cards (arcsine(% correct); higher values ~ better learning).	Approximately ~1-hour after LPS administration
Secondary	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).	Before LPS administration
Secondary	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).	Approximately ~1-hour after LPS administration
Secondary	Baseline Executive Function	Executive function: number of errors navigating a 'hidden' maze (5 trials; higher ~ worse executive function).	Before LPS administration
Secondary	Post-LPS Executive Function	Executive function: number of errors navigating a 'hidden' maze (5 trials; higher ~ worse executive function).	Approximately ~1-hour after LPS administration
Secondary	Baseline Visual-Motor Processing Speed	Visual-motor processing speed: response latency to detect a card flipped over (log10(ms); higher ~ worse processing speed).	Before LPS administration
Secondary	Post-LPS Visual-Motor Processing Speed	Visual-motor processing speed: response latency to detect a card flipped over (log10(ms); higher ~ worse processing speed).	Approximately ~1-hour after LPS administration
Secondary	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).	Before LPS administration
Secondary	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).	Approximately ~1-hour after LPS administration
Secondary	Baseline Social Cognition	Social cognition: response latency to identify the mismatched facial expression based on its emotional content (ms; log10; higher ~ worse social cognition).	Before LPS administration
Secondary	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).	Approximately ~1-hour after LPS administration
Secondary	Baseline Reward Responsiveness	Reward responsiveness will be quantified via computerized Probabilistic Reward Task	Before LPS administration
Secondary	Post-LPS Reward Responsiveness	Reward responsiveness will be quantified via computerized Probabilistic Reward Task	Approximately ~2-hour after LPS administration