Imaging the Neuroimmune System in PTSD

NCT04236986 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 20000203471R01MH110674-01A1
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

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.

Conditions

Post Traumatic Stress Disorder

Keywords

Neuroimmune System; Lipopolysaccharide

Outcome Measures

Primary Outcomes (2)

• 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)

• 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 Outcomes (12)

• Baseline Visual Attention

  Before LPS administration

• Post-LPS Visual Attention

  Approximately ~1-hour after LPS administration

• Baseline Visual Learning

  Before LPS administration

• Post-LPS Visual Learning

  Approximately ~1-hour after LPS administration

• Baseline Verbal Memory

  Before LPS administration

Study Arms (2)

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)

Drug: Lipopolysaccharide

Interventions

Lipopolysaccharide DRUG

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

Also known as: LPS

Post-LPS [11C]PBR28 PET Scan

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Yale University: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

Yale University

New Haven, Connecticut, 06519, United States

Location

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Interventions

Lipopolysaccharides

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Glycoconjugates; Carbohydrates; Polysaccharides, Bacterial; Polysaccharides; Lipids; Antigens, Bacterial; Antigens; Biological Factors; Endotoxins; Bacterial Toxins; Toxins, Biological

Results Point of Contact

• Title: Dr. Kelly Cosgrove Principal Investigator
• Organization: Yale University

kelly.cosgrove@yale.edu

2037376969

Study Officials

• Kelly Cosgrove, PhD

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: 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).

Study Record Dates

• First Submitted: January 11, 2020
• First Posted: January 22, 2020
• Study Start: March 28, 2017
• Primary Completion: May 30, 2023
• Study Completion: May 30, 2023
• Last Updated: December 9, 2024
• Results First Posted: September 26, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)