Social Experiences and Demographic Factors in the Regulation of Immune Cells

NCT06519487 | Enrolling By Invitation DMC

• 1 other identifier: 2407001
• Study Type: interventional
• Target: 480
• Locations: 1 country
• Sites: 2

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.

Conditions

Perceived Discrimination; RNA; Inflammatory Response

Outcome Measures

Primary Outcomes (8)

• Frequency of Perceived Discrimination Experiences

  Before the game, participants will be asked to complete the "Everyday Discrimination Scale" designed to measure their perceptions of discrimination encountered in their everyday lives. This instrument prompts respondents to rate the frequency of discriminatory events in their daily lives, such as "being treated with less courtesy than others." Everyday Discrimination Scale Participants provide their responses on a scale that ranges from "0" for "never" to "5" for "almost every day." The summed responses provide a measure of how frequently they experienced discrimination. The summed score can range from 0 to 50; the higher the score, the more frequently participants perceived that they experienced discrimination. Additionally, participants specify whether these experiences are due to various factors, including race and gender.

  Survey response collected before the first Cyberball Sequence within 30 minutes of arriving at the lab) and score calculated during data analysis

• Type, Timing and Frequency of Lifetime Discrimination Experiences

  The "Experiences of Discrimination Scale" measures the type, timing, and frequency of discrimination. Participants answer "yes" or "no" to 9 types of unfair treatment, such as, "Have you ever been unfairly fired?" The sum of "yes" responses ranges from 0 to 9, with a score above 6 indicating many unfair treatments. Participants also specify if the unfair treatment was due to race, skin color, or other characteristics. The sum of responses related to ancestry, race, ethnicity, or skin color indicates the frequency of racial discrimination. Additionally, participants report the last time they experienced unfair treatment due to race or ethnicity, with responses from 1 ("past week") to 4 ("more than a year"). Lower scores indicate more recent occurrences.

  Survey response collected within 30 minutes after completing the first Cyberball Sequence and score calculated during data analysis]

• Recent Discrimination and Perceived Ethnic Discrimination Score

  The sum of response scores for the Recent Discrimination (a) and Ethnic Discrimination (b) subscale items of the "General Ethnic Discrimination Scale"provides the frequency of recent discrimination experience and includes a manipulation check for the validity of the recent Cyberball condition Recent Discrimination is calculated as the sum of responses to all (a) items ranging from a choice of 1 for "never" to 6 for "almost all the time. A summed minimum score of 18 corresponds to no lifetime discrimination, and a summed maximum score of 108 corresponds to the most frequent experience of perceived lifetime discrimination. Lifetime Discrimination is calculated as the sum of all (b) item responses ranging from a choice of 1 for "never" to 6 for "almost all the time. A summed minimum score of 18 corresponds to no lifetime discrimination, and a summed maximum score of 108 corresponds to the most frequent experience of perceived lifetime discrimination.

  Survey responses collected within 30 minutes after completing the Second Cyberball Sequence and score calculated during data analysis]

• Recent and Lifetime Discrimination Stress Score

  The Cumulative response score from the Stress from Discrimination (c) items on the General Ethnic Discrimination Scale measures a person's perception of the stress of recent and lifetime unfair treatment due to a participant's racial/ethnic identity. Participants are asked to respond to the statement "How stressful was this for you?" for each discrimination experience. Response choices range from 1 for "not at all stressful" to 6 for "extremely stressful." Discrimination Stress is calculated as the sum of all (c) items on the General Ethnic Discrimination (GED) scale, where a summed score of 17 indicates little to no stress, and 102 indicates the highest amount of stress experienced due to recent and lifetime discrimination experiences.

  Survey responses collected within 30 minutes after completing the Second Cyberball Sequence and score calculated during data analysis

• Relationship between salivary and serum immune responses

  Multiplex enzyme-linked immunosorbent assays (ELISA) will allow assessment of the pg/mL concentration of inflammatory cytokines in saliva and serum. These data will be used to calculate correlation coefficients that depict the magnitude and direction of the relationship between saliva and serum inflammatory cytokine concentration. The cytokines to be measured are Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-α, and c-Reactive Protein (CRP).

  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.

• Distribution and Quantity of Immune Cells in Whole blood

  To determine the quantity of each type of peripheral blood mononuclear cells (PBMCs) available after the different Cyberball sequences, the PBMCs will be sorted and quantified from whole blood collected 30 minutes after the first and 30 minutes after the second Cyberball sequence. A Sony SH800 cell sorter is used to perform Fluorescence-Activated Cell Sorting (FACS) with appropriate antibodies to identify T cells (CD3+), B cells (CD19+), NK cells (CD56+), and monocytes (CD14+CD16-, CD14+CD16+) and counts provided of viable cells with the cell counter.

  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.

• Stimulated PBMC Cytokine Release

  Cellular Cytokine release from (PBMCs) purified from the participant's whole blood is assessed in the presence or absence of stimulation with lipopolysaccharide (LPS) toxin. The LPS incubation time will vary in length, and ELISA will measure pg/ml concentration of IL-6, TNF-α, IL-1β, CRP

  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

• Gene expression levels

  RNA expression counts and distribution will be measured in PBMCs purified from participant whole blood collected participants after completing the first and second Cyberball sequences (collection tines separated by up 2 hours)

  PMBCs purified from whole blood collected collected 30 minutes after the first and 30 minutes after the second Cyberball sequence

Secondary Outcomes (7)

• Magnitude of Race/Ethnic Residential Segregation (Dissimilarity Index)

  Questionnaire responses to the zip code items are collected within first 30 minutes in the lab and Index calculated during data analysis

• Average Community Risk Protective Factors

  Survey responses are collected within 30 minutes after completing the first Cyberball sequence and score calculated during data analysis

• Average Community Protective Factors

  Survey responses are collected within 30 minutes after completing the first Cyberball sequence and score calculated during data analysis

• Resilience

  Survey responses are collected within 30 minutes after completing the second Cyberball sequence and the average response score calculated during data analysis

• Frequency of recent stress

  Survey responses are collected within 30 minutes after completing the first Cyberball sequence and Perceived Stress score calculated during data analysis

Study Arms (12)

Mid-Atlantic: Non-Hispanic Black Order 1

EXPERIMENTAL

Participants play Cyberball™ with virtual players who appear to be non-Hispanic White. The participant only receives the ball once during the entire game, while all the non-Hispanic White avatars will pass the ball back and forth with each other many times. After completing surveys and providing saliva and blood samples, participants play Cyberball, in which they receive the ball from virtual players an equal number of times as the other avatars, regardless of their ethnicity. During this round, participants play cyberball with virtual players who do not have any obvious ethnic differences from them. The participant again only receives the ball once during the entire game, while the other avatars that look similar to them pass the ball back and forth with each other a number of times. After completing surveys and providing blood samples, participants receive the ball from virtual players an equal number of times as the other avatars, regardless of their ethnicity.

Behavioral: Cyberball

Mid-Atlantic: Non-Hispanic Black Order 2

ACTIVE COMPARATOR

Participants play Cyberball with virtual players who do not have any noticeable ethnic differences from them. The participants only receive the ball once during the entire game, but avatars that look similar to them pass the ball back and forth with each other several times. After completing surveys and providing saliva and blood samples, participants play Cyberball again but receive the ball from virtual players an equal number of times as the other avatars, regardless of the avatars' ethnicity. Participants play another session of Cyberball™ with virtual players who appear to be non-Hispanic White. The participant only receives the ball once during the entire game, while all the non-Hispanic White avatars will pass the ball back and forth with each other many times. After completing surveys and providing blood samples, participants again play Cyberball but receive the ball from virtual players an equal number of times as the other avatars, regardless of the avatars' ethnicity.

Behavioral: Cyberball

Mid-Atlantic: Non-Hispanic White Order 1

EXPERIMENTAL

Participants play Cyberball™ with virtual players who appear non-Hispanic Black, or Hispanic. The participant receives the ball once during the game, while all the non-Hispanic Black or Hispanic avatars will pass the ball back and forth with each other many times. After completing surveys and providing saliva and blood samples, participants play Cyberball, in which they receive the ball from virtual players an equal number of times as the other avatars, regardless of their ethnicity. During this round, participants play cyberball with virtual players who do not have any noticeable ethnic differences from them. The participant again only receives the ball once during the entire game, while the other avatars that look similar to them pass the ball back and forth several times. After completing surveys and providing blood samples, participants receive the ball from virtual players an equal number of times as the other avatars, regardless of their ethnicity.

Behavioral: Cyberball

Mid-Atlantic: Non-Hispanic White Order 2

ACTIVE COMPARATOR

Participants play Cyberball with virtual players who do not have any noticeable ethnic differences from them. The participants only receive the ball once during the game, but avatars that look similar to them pass the ball back and forth with each other several times. After completing surveys and providing saliva and blood samples, participants play Cyberball again but receive the ball from virtual players an equal number of times as the other avatars, regardless of the avatars' ethnicity. Participants play another session of Cyberball with virtual players who appear to be non-Hispanic Black or Hispanic. The participant receives the ball once during the game, while all the non-Hispanic Black or Hispanic avatars will pass the ball back and forth with each other many times. After completing surveys and providing blood samples, participants again play Cyberball but receive the ball from virtual players an equal number of times as the other avatars, regardless of the avatars' ethnicity.

Behavioral: Cyberball

Mid-Atlantic Hispanic Order 1

EXPERIMENTAL

Participants play Cyberball™ with virtual players who appear to be non-Hispanic White. The participant receives the ball once during the game, while all the non-Hispanic White avatars will pass the ball back and forth with each other many times. After completing surveys and providing saliva and blood samples, participants play Cyberball, in which they receive the ball from virtual players an equal number of times as the other avatars, regardless of their ethnicity. During this round, participants play Cyberball with virtual players who do not have any noticeable ethnic differences from them. The participant again only receives the ball once during the entire game, while the other avatars that look similar to them pass the ball back and forth several times. After completing surveys and providing blood samples, participants receive the ball from virtual players an equal number of times as the other avatars, regardless of their ethnicity.

Behavioral: Cyberball

Mid-Atlantic Hispanic Order 2

ACTIVE COMPARATOR

Participants play Cyberball with virtual players who do not have any noticeable ethnic differences from them. The participants only receive the ball once during the entire game, but avatars that look similar to them pass the ball back and forth with each other several times. After completing surveys and providing saliva and blood samples, participants play Cyberball again but receive the ball from virtual players an equal number of times as the other avatars, regardless of the avatars' ethnicity. Participants play another session of Cyberball™ with virtual players who appear to be non-Hispanic White. The participant only receives the ball once during the entire game, while all the non-Hispanic White avatars will pass the ball back and forth with each other many times. After completing surveys and providing blood samples, participants again play Cyberball but receive the ball from virtual players an equal number of times as the other avatars, regardless of the avatars' ethnicity.

Behavioral: Cyberball

Southwest Non-Hispanic Black Order 1

EXPERIMENTAL

Participants play Cyberball™ with virtual players who appear to be non-Hispanic White. The participant only receives the ball once during the entire game, while all the non-Hispanic White avatars will pass the ball back and forth with each other many times. After completing surveys and providing saliva and blood samples, participants play Cyberball, in which they receive the ball from virtual players an equal number of times as the other avatars, regardless of their ethnicity. During this round, participants play cyberball with virtual players who do not have any noticeable ethnic differences from them. The participant again only receives the ball once during the entire game, while the other avatars that look similar to them pass the ball back and forth several times. After completing surveys and providing blood samples, participants receive the ball from virtual players an equal number of times as the other avatars, regardless of their ethnicity.

Behavioral: Cyberball

Southwest Non-Hispanic Black Order 2

ACTIVE COMPARATOR

Participants play Cyberball with virtual players who do not have any noticeable ethnic differences from them. The participants only receive the ball once during the entire game, but avatars that look similar to them pass the ball back and forth with each other several times. After completing surveys and providing saliva and blood samples, participants play Cyberball again but receive the ball from virtual players an equal number of times as the other avatars, regardless of the avatars' ethnicity. Participants play another session of Cyberball™ with virtual players who appear to be non-Hispanic White. The participant only receives the ball once during the entire game, while all the non-Hispanic White avatars will pass the ball back and forth with each other many times. After completing surveys and providing blood samples, participants again play Cyberball but receive the ball from virtual players an equal number of times as the other avatars, regardless of the avatars' ethnicity.

Behavioral: Cyberball

Southwest Non-Hispanic White Order 1

EXPERIMENTAL

Participants play Cyberball™ with virtual players who appear non-Hispanic Black or Hispanic. The participant receives the ball once during the game, while all the non-Hispanic Black or Hispanic avatars will pass the ball back and forth with each other many times. After completing surveys and providing saliva and blood samples, participants play Cyberball, in which they receive the ball from virtual players an equal number of times as the other avatars, regardless of their ethnicity. During this round, participants play cyberball with virtual players who do not have any noticeable ethnic differences from them. The participant again only receives the ball once during the entire game, while the other avatars that look similar to them pass the ball back and forth with each other several times. After completing surveys and providing blood samples, participants receive the ball from virtual players an equal number of times as the different avatars, regardless of ethnicity.

Behavioral: Cyberball

Southwest Non-Hispanic White Order 2

ACTIVE COMPARATOR

Participants play Cyberball with virtual players who do not have any noticeable ethnic differences from them. The participants only receive the ball once during the entire game, but avatars that look similar to them pass the ball back and forth with each other several times. After completing surveys and providing saliva and blood samples, participants play Cyberball again but receive the ball from virtual players an equal number of times as the other avatars, regardless of their ethnicity. Participants play another session of Cyberball with virtual players who appear to be non-Hispanic Black or Hispanic. The participant only receives the ball once during the entire game, while all the non-white avatars will pass the ball back and forth with each other many times. After completing surveys and providing blood samples, participants again play Cyberball but receive the ball from virtual players an equal number of times as the other avatars, regardless of the avatars' ethnicity.

Behavioral: Cyberball

Southwest Hispanic Order 1

EXPERIMENTAL

Participants play Cyberball™ with virtual players who appear to be non-Hispanic White. The participant only receives the ball once during the entire game, while all the non-Hispanic White avatars will pass the ball back and forth with each other many times. After completing surveys and providing saliva and blood samples, participants play Cyberball, in which they receive the ball from virtual players an equal number of times as the other avatars, regardless of their ethnicity. During this round, participants play Cyberball with virtual players who do not have any noticeable ethnic differences from them. The participant again only receives the ball once during the entire game, while the other avatars that look similar to them pass the ball back and forth several times. After completing surveys and providing blood samples, participants receive the ball from virtual players an equal number of times as the other avatars, regardless of their ethnicity.

Behavioral: Cyberball

Southwest Hispanic White Order 2

EXPERIMENTAL

Participants play Cyberball with virtual players who do not have any noticeable ethnic differences from them. The participants only receive the ball once during the entire game, but avatars that look similar to them pass the ball back and forth with each other several times. After completing surveys and providing saliva and blood samples, participants play Cyberball again but receive the ball from virtual players an equal number of times as the other avatars, regardless of the avatars' ethnicity. Participants play another session of Cyberball™ with virtual players who appear to be non-Hispanic White. The participant receives the ball once during the game, while all the non-Hispanic White avatars will pass the ball back and forth with each other many times. After completing surveys and providing blood samples, participants again play Cyberball but receive the ball from virtual players an equal number of times as the other avatars, regardless of the avatars' ethnicity.

Behavioral: Cyberball

Interventions

Cyberball BEHAVIORAL

Cyberball™ is a virtual social exclusion game that simulates social interactions and acute discrimination experiences in a controlled laboratory setting. The game involves passing a virtual ball between players represented by images. In this study, only the participant is a real player, while the other "players" are pre-programmed virtual avatars controlled by the experimenter using Cyberball software. The ethnicity of these virtual players can be manipulated by changing the stock photos used to represent them. Participants in the Race-Based Social Exclusion condition play Cyberball with virtual players who appear to be of a different ethnicity from the participant. In the Non-Race-Based Social Exclusion, the participant plays with virtual players who do not have any obvious ethnic differences from the participant, and social inclusion is a washout condition where the participant receives the ball from the virtual players, regardless of the ethnicity of the avatars.

Mid-Atlantic Hispanic Order 1; Mid-Atlantic Hispanic Order 2; Mid-Atlantic: Non-Hispanic Black Order 1; Mid-Atlantic: Non-Hispanic Black Order 2; Mid-Atlantic: Non-Hispanic White Order 1; Mid-Atlantic: Non-Hispanic White Order 2; Southwest Hispanic Order 1; Southwest Hispanic White Order 2; Southwest Non-Hispanic Black Order 1; Southwest Non-Hispanic Black Order 2; Southwest Non-Hispanic White Order 1; Southwest Non-Hispanic White Order 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Morgan State University: lead
• Texas Christian University: collaborator
• University of Maryland, Baltimore: collaborator
• University of Baltimore: collaborator

Study Sites (2)

Morgan State University

Baltimore, Maryland, 21251, United States

Location

Texas Christian University

Fort Worth, Texas, 76129, United States

Location

MeSH Terms

Conditions

Perceived Discrimination

Condition Hierarchy (Ancestors)

Social Discrimination; Social Behavior; Behavior

Study Officials

• Ingrid K Tulloch, PhD

  Morgan State University

  PRINCIPAL INVESTIGATOR

• Sarah E Hill, PhD

  Texas Christian University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: The participant and the outcomes assessor will be blinded to the conditions to reduce bias. Participants will not be informed about the specific conditions (race-based exclusion or non-race-based exclusion) they are experiencing during Cyberball game and will be instructed not to discuss their experiences with the investigator or the outcomes assessor. All participant's questionnaire responses, blood, and saliva samples are labeled with anonymized codes (computer-generated ID numbers) to prevent identification of the condition order and Cyberball randomizes sequences automatically. The outcomes assessor, who will analyze the blood and saliva samples for immune cell function and genomic and epigenetic markers and the questionnaire, will be unaware of the participants' assigned conditions. Data analysis will be performed on de-identified datasets and randomization managed by a separate team member not involved in data collection or analysis.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: 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.

Study Record Dates

• First Submitted: July 18, 2024
• First Posted: July 25, 2024
• Study Start: February 27, 2025
• Primary Completion (Estimated): June 3, 2028
• Study Completion (Estimated): June 3, 2028
• Last Updated: May 5, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Data will become available at the end of the study period or as summary data are published in research reports (whichever comes first). The cleaned data files will be available at ) OpenICPSR or another field-specific repository listed at Repositories for Sharing Scientific Data to allow for management and sharing according to NIH guidelines and remain as long as allowed by NIH
• Access Criteria: Deidentified data will be available by written permission.

Locations

US (2)