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| ID | Type | Description | Link |
|---|---|---|---|
| 1R01MH110674-01A1 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Mental Health (NIMH) | NIH |
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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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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) |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lipopolysaccharide | Drug | LPS will be administered intravenously (1.0ng/kg; IV) |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| Baseline Visual Attention | Visual attention: response latency to identify card color (log10(ms); higher ~ worse attention). | Before LPS administration |
| Post-LPS Visual Attention | Visual attention: response latency to identify card color (log10(ms); higher ~ worse attention). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Kelly Cosgrove, PhD | Yale University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Yale University | New Haven | Connecticut | 06519 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Healthy Controls AKA Trauma Exposed Individuals Without PTSD For HIC 2000020347 | We will recruit men and women aged 18-55 who have been exposed to trauma without PTSD into the study. Men and women, aged 18-55 years, any race, with a history of trauma exposure. Trauma-exposed controls will have a CAPS-5 score of 0-22 (no/minimal to mild/subthreshold symptoms) Able to read and write English and to provide voluntary, written informed consent |
| FG001 | PTSD Controls for HIC 2000020347 | We will recruit men and women aged 18-55 who have been exposed to trauma with PTSD into the study. Men and women, aged 18-55 years, any race, with a history of PTSD, Subjects with posttraumatic stress disorder (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 |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Healthy Controls AKA Trauma Exposed Individuals Without PTSD For HIC 2000020347 | We will recruit men and women aged 18-55 who have been exposed to trauma without PTSD into the study. Men and women, aged 18-55 years, any race, with a history of trauma exposure. Trauma-exposed controls will have a CAPS-5 score of 0-22 (no/minimal to mild/subthreshold symptoms) Able to read and write English and to provide voluntary, written informed consent |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Posted | Mean | Standard Deviation | mL/cm3 | Before LPS administration (baseline) |
|
Subjects will be followed for 1 month after LPS injection and second PET scan.
this study will be monitored every 6 months by a Data Safety Monitoring Board (DSMB). Adequate surveillance and protections will be put in place to discover adverse events promptly and keep their effects to a minimum. There is an established DSMB at the Yale PET Center that meets every 6 months.
Expected and Unexpected Adverse Events will be recorded according to PET Center and NIH guidelines
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Healthy Controls AKA Trauma Exposed Individuals Without PTSD For HIC 2000020347 | We will recruit men and women aged 18-55 who have been exposed to trauma without PTSD into the study. Men and women, aged 18-55 years, any race, with a history of trauma exposure. Trauma-exposed controls will have a CAPS-5 score of 0-22 (no/minimal to mild/subthreshold symptoms) Able to read and write English and to provide voluntary, written informed consent |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dull ache Loose Bowels | General disorders | Non-systematic Assessment | Dull ache and loose bowels(diarrhea) post aline placement 2022-01-28, Date confirmed 02-02-2022 Self Resolved. Ache most likely attributed to aline placement. Loose bowels self resolved, cause unknown. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Kelly Cosgrove Principal Investigator | Yale University | 2037376969 | kelly.cosgrove@yale.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Dec 20, 2022 | May 2, 2024 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form: ICF form 4 | Nov 11, 2020 | May 9, 2024 | ICF_001.pdf |
| ICF | No | No | Yes | Informed Consent Form: ICF form 1 2 5 | Nov 11, 2020 | May 9, 2024 | ICF_002.pdf |
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| ID | Term |
|---|---|
| D013313 | Stress Disorders, Post-Traumatic |
| ID | Term |
|---|---|
| D040921 | Stress Disorders, Traumatic |
| D000068099 | Trauma and Stressor Related Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D008070 | Lipopolysaccharides |
| ID | Term |
|---|---|
| D006001 | Glycoconjugates |
| D002241 | Carbohydrates |
| D011135 | Polysaccharides, Bacterial |
| D011134 | Polysaccharides |
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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).
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| Approximately ~1-hour after LPS administration |
| Baseline Visual Learning | Visual learning: % of correctly identified repeat cards (arcsine(% correct); higher values ~ better learning). | Before LPS administration |
| Post-LPS Visual Learning | Visual learning: % of correctly identified repeat cards (arcsine(% correct); higher values ~ better learning). | Approximately ~1-hour after LPS administration |
| Baseline Verbal Memory | 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. | Before LPS administration |
| Post-LPS Verbal Memory | 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. | Approximately ~1-hour after LPS administration |
| Baseline Executive Function | Executive function: summed number of errors navigating a 'hidden' maze (5 trials; higher ~ worse executive function). | Before LPS administration |
| Post-LPS Executive Function | Executive function: summed number of errors navigating a 'hidden' maze (5 trials; higher ~ worse executive function). | Approximately ~1-hour after LPS administration |
| 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 |
| 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 |
| 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 |
| 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 |
| BG001 | PTSD Controls for HIC 2000020347 | We will recruit men and women aged 18-55 who have been exposed to trauma with PTSD into the study. Men and women, aged 18-55 years, any race, with a history of PTSD, Subjects with posttraumatic stress disorder (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 |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | 3 subjects withdrew from HC population and 1 subject from PTSD population withdrew, prior to second PET scan and LPS injection. | Count of Participants | Participants |
|
| Race (NIH/OMB) | 3 healthy controls and 1 PTSD participant declined to continue/withdrew from study prior to second PET scan/LPS | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| PTSD Controls for HIC 2000020347 |
We will recruit men and women aged 18-55 who have been exposed to trauma with PTSD into the study. Men and women, aged 18-55 years, any race, with a history of PTSD, Subjects with posttraumatic stress disorder (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 |
|
|
| 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. | Posted | Mean | Standard Deviation | mL/cm3 | 3-hours after LPS administration (1.0 ng/kg; IV) |
|
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| Secondary | Baseline Visual Attention | Visual attention: response latency to identify card color (log10(ms); higher ~ worse attention). | Posted | Mean | Full Range | log10(ms) | Before LPS administration |
|
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| Secondary | Post-LPS Visual Attention | Visual attention: response latency to identify card color (log10(ms); higher ~ worse attention). | Posted | Mean | Full Range | log10(ms) | Approximately ~1-hour after LPS administration |
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| Secondary | Baseline Visual Learning | Visual learning: % of correctly identified repeat cards (arcsine(% correct); higher values ~ better learning). | Posted | Mean | Full Range | percentage of correct responses | Before LPS administration |
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| Secondary | Post-LPS Visual Learning | Visual learning: % of correctly identified repeat cards (arcsine(% correct); higher values ~ better learning). | Posted | Mean | Full Range | percentage of correct responses | Approximately ~1-hour after LPS administration |
|
|
|
| Secondary | Baseline Verbal Memory | 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. | Posted | Mean | Full Range | Number of correct responses | Before LPS administration |
|
|
|
| Secondary | Post-LPS Verbal Memory | 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. | Posted | Mean | Full Range | Number of correct responses | Approximately ~1-hour after LPS administration |
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| Secondary | Baseline Executive Function | Executive function: summed number of errors navigating a 'hidden' maze (5 trials; higher ~ worse executive function). | Posted | Mean | Full Range | Number of errors | Before LPS administration |
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| Secondary | Post-LPS Executive Function | Executive function: summed number of errors navigating a 'hidden' maze (5 trials; higher ~ worse executive function). | Posted | Mean | Full Range | Number of errors | Approximately ~1-hour after LPS administration |
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| Secondary | Baseline Visual-Motor Processing Speed | Visual-motor processing speed: response latency to detect a card flipped over (log10(ms); higher ~ worse processing speed). | Posted | Mean | Full Range | log10(ms) | Before LPS administration |
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| 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). | Posted | Mean | Full Range | log10(ms) | Approximately ~1-hour after LPS administration |
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| 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). | Data were not collected. | Posted | Before LPS administration |
|
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| 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). | Data were not collected. | Posted | Approximately ~1-hour after LPS administration |
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| 0 |
| 18 |
| 0 |
| 18 |
| 1 |
| 18 |
| EG001 | PTSD Controls for HIC 2000020347 | We will recruit men and women aged 18-55 who have been exposed to trauma with PTSD into the study. Men and women, aged 18-55 years, any race, with a history of PTSD, Subjects with posttraumatic stress disorder (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 | 0 | 16 | 0 | 16 | 0 | 16 |
|
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| D008055 |
| Lipids |
| D000942 | Antigens, Bacterial |
| D000941 | Antigens |
| D001685 | Biological Factors |
| D004731 | Endotoxins |
| D001427 | Bacterial Toxins |
| D014118 | Toxins, Biological |
| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| Insula |
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| vmPFC |
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