Clinical trial NCT06519487: Social Experiences and Demographic Factors in the Regulation of Immune Cells
Official title: Perceived Discrimination, Geography, and Demographic Effects on Immune Cell Function and Regulation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Perceived Discrimination
RNA
Inflammatory Response
Lead sponsor: Morgan State University
Sponsor class: OTHER
Collaborators: name: Texas Christian University
name: University of Maryland, Baltimore
name: University of Baltimore
First posted: 2024-07-25
Enrollment: 480
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: A crossover model is used to investigate whether geography, race, and ethnicity, interacting with laboratory discrimination conditions, affect immune cell function through genomic and epigenetic mechanisms, with perceived discrimination moderating the immune outcomes. Participants from each geographic region and belonging to one of three race or ethnic groups will experience race-based and non-race-based social exclusion and "washout" phases to mitigate carryover effects. For instance, participants might first experience race-based social exclusion, followed by an inclusion period (washout), and then non-race-based social exclusion, followed by another washout. Blood samples will be collected after each social exclusion to measure immune responses. Each participant will serve as their own control, facilitating within-subject comparisons to reduce variability due to individual differences, except on the variables of interest.
Primary purpose: BASIC_SCIENCE

Brief summary: Immune-mediated inflammatory diseases are a health burden for approximately seven percent of the population of Western nations. Preliminary data suggest variations in ethnic identity and/or geography influence discrimination experiences and inflammatory response trends. This study investigates how geography, ethnicity, and laboratory manipulation of discrimination experiences affect immune cell function and genomic regulation. Flow cytometry and immune cell stimulation will test monocytes collected from peripheral blood for functional effects. Next-generation transcriptomics and epigenomics will assess genomic and epigenetic mechanisms. The hypothesis is that geography, self-identified race, and ethnicity, interacting with laboratory discrimination conditions during the virtual ballgame Cyberball™, significantly affect immune cell function through genomic and epigenetic mechanisms, with perceived discrimination as a moderating factor on the immune outcomes. The transdisciplinary nature of the proposed study aims to provide valuable insights into differential susceptibility to immune-mediated inflammatory diseases across diverse populations. Uncovering these insights will better inform population-relevant interventions for immune-mediated inflammatory diseases.

Detailed description: More than a third of the residents of the United States suffer from a chronic disease, with almost half involving dysregulated immune processes. Immune-mediated inflammatory diseases pose a public health burden in the United States. Preliminary data from previous work suggest that variations in ethnic identity and geography might influence discrimination experiences and inflammatory response trends. To investigate the functional implications of these findings, a multi-institutional study is proposed, examining how social experiences and demographic factors predict the regulation and activity of immune cells. Specifically, the hypothesis is that geography, self-identified race, and ethnicity, interacting with laboratory discrimination conditions, significantly affect immune cell function through genomic and epigenetic mechanisms, with perceived discrimination moderating the immune outcomes. Participants will provide saliva samples, complete psychosocial and demographic questionnaires, and play the virtual social exclusion game Cyberball™ in a randomly assigned block order. Acute discrimination experiences are manipulated by conditions during Cyberball. Virtual players, who appear to be of a different race from the participant, exclude them by not passing the participant the ball in the race-based exclusion condition. In the inclusion condition, the participant receives the ball regardless of participant and virtual player race. In the general social exclusion (not race-based), the players and participant races are similar to the inclusion condition, except that the participant does not receive the ball. The block of Cyberball and blood draws randomly assigned are either: 1) race-based social exclusion and inclusion first, a blood draw, then non-race-based social exclusion, inclusion, and blood draw, or 2) non-race-based social exclusion and inclusion, a blood draw and then the race-based social exclusion and inclusion and a blood draw. Baseline and post-first block inflammatory responses in saliva will be measured using enzyme-linked immunosorbent assays (ELISAs) to determine the concentration of cytokines like C-reactive protein, interleukin-6, and tumor necrosis factor-alpha. Flow cytometry and immune cell stimulation with toxin will test monocytes purified and sorted from the participant's blood for functional effects. Next-generation transcriptomics and epigenomics will assess differentially expressed RNA and methylation enrichment, emphasizing genes involved in inflammation signaling pathways. The data will be statistically analyzed using regression analysis and structural equation modeling to determine the relationship between discrimination, geography, immune cell function, and regulation while controlling for other socio-demographic factors. The findings could inform public health initiatives and interventions to reduce health disparities and improve outcomes for marginalized communities.

Eligibility criteria: Inclusion Criteria:

* Non-Hispanic Black, Non-Hispanic White, or Hispanic
* At least 18 years of age
* Lives within 25 miles of, works, or attends Morgan State University, The University of Baltimore or Texas Christian University

Exclusion Criteria:

* Anyone not identifying as either non-Hispanic Black, non-Hispanic White, or Hispanic,
* Under 18 years old
* Does not live within 25 miles of, works, or attends Morgan State University, the University of Baltimore or Texas Christian University

Primary outcomes:
measure: Frequency of Perceived Discrimination Experiences
timeFrame: Survey response collected before the first Cyberball Sequence within 30 minutes of arriving at the lab) and score calculated during data analysis
measure: Type, Timing and Frequency of Lifetime Discrimination Experiences
timeFrame: Survey response collected within 30 minutes after completing the first Cyberball Sequence and score calculated during data analysis]
measure: Recent Discrimination and Perceived Ethnic Discrimination Score
timeFrame: Survey responses collected within 30 minutes after completing the Second Cyberball Sequence and score calculated during data analysis]
measure: Recent and Lifetime Discrimination Stress Score
timeFrame: Survey responses collected within 30 minutes after completing the Second Cyberball Sequence and score calculated during data analysis
measure: Relationship between salivary and serum immune responses
timeFrame: Samples used in assay are saliva collected at baseline (30 mins before) and 40 minutes after the first Cyberball sequence, and serum is purified from whole blood collected 30 minutes after the first and second Cyberball sequence.
measure: Distribution and Quantity of Immune Cells in Whole blood
timeFrame: These data will be from whole blood samples collected 30 minutes after the first and 30 minutes after the second Cyberball sequence. The sequences are between 90 to 120 minutes apart separated by a washout period.
measure: Stimulated PBMC Cytokine Release
timeFrame: PMBCs purified from whole blood collected collected 30 minutes after the first and 30 minutes after the second Cyberball sequence are compared at 0, 2, 24 and 26 hours after incubation in LPS
measure: Gene expression levels
timeFrame: PMBCs purified from whole blood collected collected 30 minutes after the first and 30 minutes after the second Cyberball sequence
Secondary outcomes:
measure: Magnitude of Race/Ethnic Residential Segregation (Dissimilarity Index)
timeFrame: Questionnaire responses to the zip code items are collected within first 30 minutes in the lab and Index calculated during data analysis
measure: Average Community Risk Protective Factors
timeFrame: Survey responses are collected within 30 minutes after completing the first Cyberball sequence and score calculated during data analysis
measure: Average Community Protective Factors
timeFrame: Survey responses are collected within 30 minutes after completing the first Cyberball sequence and score calculated during data analysis
measure: Resilience
timeFrame: Survey responses are collected within 30 minutes after completing the second Cyberball sequence and the average response score calculated during data analysis
measure: Frequency of recent stress
timeFrame: Survey responses are collected within 30 minutes after completing the first Cyberball sequence and Perceived Stress score calculated during data analysis
measure: Degree of Morbidity
timeFrame: Survey responses are collected within 30 minutes after completing the second Cyberball sequence and the sum of response scores calculated during data analysis
measure: Methylation Score
timeFrame: Methylsequencing of PMBCs purified from whole blood collected collected 30 minutes after the first and 30 minutes after the second Cyberball sequence
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Morgan State University
state: Maryland
city: Fort Worth
country: United States
facility: Texas Christian University
state: Texas
Study officials:
References: