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Psychology, SocialPhase 4BSBNCT05654441

Body and Social Behavior

A Phase 4 study testing Influenza vaccine in people with Psychology, Social and Inflammation, run by University of North Carolina, Chapel Hill at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This randomized, double-blind, placebo-controlled study of the influenza vaccine will shed important light on how the immune system responds to different positive and negative social experiences. Read more about this study

Who is it for?
Ages 18 to 35 yearsHealthy volunteers can take part
Conditions the study is for
Psychology, Social, Inflammation, Defeat, Social
What is being tested?
Influenza vaccine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
104 participants
Where
2 sitesUnited States
Study dates
17 Oct 2022to 15 Dec 2023
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 35 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 18-35 years old
  • Have a same-gender friend willing to participate in the second study session

Who cannot join

  • Are not a student
  • Have already received the annual influenza vaccine or had the flu this season
  • Report current illness/sickness symptoms, including upper respiratory symptoms
  • Report any major medical conditions (e.g., diabetes, asthma)
  • Use mood or immune altering medications (e.g., anti-depressants)
  • Current regular nicotine/tobacco use (i.e., daily use of cigarettes or e-cigarettes)
Show all 15Show fewer
  • Have an allergy to eggs
  • Have had COVID-19 in past two weeks
  • Current or history of depression or anxiety
  • Have had Guillain-Barre Syndrome
  • Are allergic to vaccine or ingredients present in vaccine
  • Have had an adverse reaction to a blood draw, including to needles or sight or blood
  • Weigh less than 110 pounds
  • Are unwilling to be video/audio recorded during the social interaction tasks
  • Are unwilling to be unmasked during the social interaction tasks

Trial locations and contacts

2 sites in 1 country.

United States2 sites
  • Clinical and Translation Research Center

    Chapel Hill, North Carolina, 27514

  • Howell Hall

    Chapel Hill, North Carolina, 27599

Other trials in United States

About this study

Official title: Low-grade Inflammatory Challenge and Social Behavior

This randomized, double-blind, placebo-controlled study of the influenza vaccine will shed important light on how the immune system responds to different positive and negative social experiences. Building on the nuanced animal literature showing that, while animals exposed to an inflammatory challenge show reductions in social exploration consistent with the sickness behavior of social withdrawal, they actually show increases in social engagement behavior during interactions with a cage mate or pair-bonded animal. The present study will examine if a mild inflammatory challenge (receipt of the influenza vaccine) leads to change in actual social behavior in interactions, specifically toward a stranger and separately, toward a close friend. This study will also build on foundational animal research showing that an inflammatory challenge leads to social defeat behaviors in animals.

Read the detailed description

Psychologists have long appreciated that the mind can impact the body, and that bodily changes can influence the mind. Social psychologists in particular have conducted pioneering work on connections between the mind and body, showing both that social experiences elicit changes in numerous physiological systems and that physiological changes influence social cognition and behavior. Until recently, however, little attention has been paid to the connections between social experiences and the immune system. This is a critical gap knowledge, as seminal animal work shows that there are profound relationships between social experiences and immune system functioning that have yet to be fully explored in humans. Further, there are strong theoretical reasons to suspect that the immune system matters for social psychological processes even beyond times of sickness, though many of these connections are yet to be uncovered empirically in humans. Thus, to develop a comprehensive understanding of the mind-body connections that drive social behavior, researchers must integrate the immune system.

To address this critical gap in knowledge, the present study will examine the body-to-mind connection between the immune system and positive (i.e., interacting with a close other) and negative (i.e., social defeat) social experiences.

Why does the immune system matter for social behavior? There are good theoretical reasons why the immune system would be tightly interconnected to even normative, everyday social experiences beyond times of sickness. First, despite the common belief that the immune system only comes "online" in response to pathogens or physical injury, the immune system is in fact always active and fluctuates considerably even in the absence of an acute infection. Indeed, the immune system is responsive to both real and imagined situations that may signal increased probability of injury or infection. This includes everyday social experiences and situations of greater interest to social psychologists, from falling in love to being socially ostracized. Second, the brain is constantly monitoring the physiological state of the body and integrating this interoceptive information with signals from the broader environment to anticipate current and future metabolic demands and guide adaptive behavior. Thus, even relatively minor fluctuations in immune system activation beyond times of sickness can feed back to the brain to guide social cognition and behavior. In sum, there are strong theoretical reasons why everyday, normative social experiences may affect and be affected by immune system activation.

To date, social withdrawal is considered a hallmark "sickness behavior", based on both animal and human work showing that experimentally-induced increases in inflammation lead to less social exploration and greater feelings of social disconnection. However, other animal work suggests that the effects of inflammation on social behavior may be more nuanced than uniform social withdrawal, as some research shows that animals spend more time huddling with familiar cagemates, and form pair bonds more quickly when exposed to an inflammatory challenge. Further, recent work in the field of psychoneuroimmunology with humans replicates this, showing that an inflammatory challenge causes heightened (not diminished) neural responses to reminders of social connection. Yet to date, no known human work has examined if an inflammatory challenge causes changes in actual social behavior in humans, a critical next step in this line of research. Techniques from experimental social psychology are ideally-suited to address this next step, as social psychology has been at the cutting-edge of developing tools for eliciting and quantifying social behavior, particularly in the context of dyadic interactions that are likely to be important during an inflammatory challenge. This study will bring this important perspective to bear to further understanding of how immune system activation may cause changes in social behavior.

There is a storied history in psychoneuroimmunology (PNI) of using vaccines (e.g., influenza, typhoid) as a way to study immune system functioning. In vaccine trials, researchers typically examine how individual-differences in psychological processes (e.g., depressive symptoms, social connection) influence the effectiveness of the vaccine by examining the number of antibody titers produced following vaccination as a function of the individual-difference of interest. More recently, researchers have begun to use the influenza vaccine as a way to manipulate levels of inflammation, as the vaccine produces a small, but significant, increase in inflammatory markers (e.g., interleukin-6) in the 24-hours following vaccination administration. Prior work has examined the impact of vaccine-induced increases in inflammation on psychological processes such as mood and reward processing and shown that within-subject changes in inflammation in response to the influenza vaccine predict increases in daily negative affect and increases in reward responsivity. The present project will build on this prior work by adding a placebo-controlled (saline) condition, thus allowing researchers to determine if vaccine-induced changes in inflammation cause changes in social behavior. Using the influenza vaccine as an inflammatory challenge has numerous advantages over prior approaches: 1) It provides a public health service to the local community (i.e., given that vaccinations can prevent viral outbreaks) rather than making participants temporarily ill, as in the rhinovirus studies and endotoxin studies discussed previously; 2) The change in inflammation elicited by the vaccine is relatively small, thus mirroring more normative, day-to-day fluctuations in inflammation beyond times of sickness; and 3) Experimental procedures are less resource and cost-intensive, as almost every local pharmacy provides influenza vaccinations, and the cost is often covered by insurance and is relatively low (or free) for the uninsured. Given these advantages, the present study will use the influenza vaccine to examine if an experimental manipulation of inflammation causes changes in social behavior of interest to both social psychologists and psychoneuroimmunologists. In doing so, the study will advance a method that can be widely adopted by researchers to study how immune system activation feeds back to the brain to influence social experience.

Being tested
Influenza vaccine, Placebo
Medical subject headings
Inflammation, Social Defeat

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Influenza vaccineBiological

    0.5 mL single-dose injection

  • PlaceboBiological

    Also called Saline Injection

    0.5 mL single-dose injection with no therapeutic effect

Study groups in NCT05654441
Study groupRoleWhat they receive
Influenza VaccineExperimentalExperimental group given influenza vaccine (Flulaval)
Receives: Biological: Influenza vaccine
Sham VaccinePlacebo comparatorThe control group given a placebo (saline injection)
Receives: Biological: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. IL-6 Levels 24 Hours After Vaccine

    The investigators will examine levels of IL-6 measured in plasma 24-hours following the vaccine.

    Measured: within approximately 24 hours of treatment

  2. IL-10 Levels 24 Hours After Vaccine

    The investigators will examine levels of IL-10 measured in plasma 24-hours following the vaccine.

    Measured: within approximately 24 hours of treatment

  3. TNF-alpha Levels 24 Hours After Vaccine

    The investigators will examine levels of TNF-alpha measured in plasma 24-hours following the vaccine.

    Measured: within approximately 24 hours of treatment

  4. IFN-gamma Levels 24 Hours After Vaccine

    The investigators will examine levels of IFN-gamma measured in plasma 24-hours following the vaccine.

    Measured: within approximately 24 hours of treatment

Secondary outcomes (7)
  1. Sickness Symptom Scores

    The investigators will examine if there are differences in self-reported sickness symptoms, as measured by the Sickness Questionnaire, as a function of vaccine condition. The 10-item Sickness Questionnaire includes Likert-type questions using a 4- point scale, the total range is 0-30 with higher scores indicating greater sickness symptoms.

    Measured: within approximately 24 hours of treatment

  2. High Arousal Negative Affect Scores

    he investigators will examine if there are differences in self-reported high arousal negative affect, as measured by a subscale of the Positive Affect-Negative Affect Schedule-X, as a function of vaccine condition. Participants indicated the extent to which they felt each of 11 high arousal negative emotions (i.e., "angry", "irritable", "nervous", "scared", "upset", "afraid", "ashamed", "distressed", "frustrated", "hostile", "jittery") on a 0 (not at all) -100 (extremely) sliding scale. Responses were then averaged with higher scores indicating greater high arousal negative affect.

    Measured: within approximately 24 hours of treatment

  3. Low Arousal Negative Affect Scores

    The investigators will examine if there are differences in self-reported low arousal negative affect, as measured by a subscale of the Positive Affect-Negative Affect Schedule-X, as a function of vaccine condition. Participants indicated the extent to which they felt each of four low arousal negative emotions (i.e., "bored", "guilty", "sad", "worn out") on a 0 (not at all) -100 (extremely) sliding scale. Responses were then averaged with higher scores indicating greater low arousal negative affect.

    Measured: within approximately 24 hours of treatment

  4. High Arousal Positive Affect Scores

    The investigators will examine if there are differences in self-reported high arousal positive affect, as measured by a subscale of the Positive Affect-Negative Affect Schedule-X, as a function of vaccine condition. Participants indicated the extent to which they felt each of 10 high arousal positive emotions (i.e., "amused," "determined," "enthusiastic," "excited," "happy," "inspired", "proud," "strong," "active," "alert") on a 0 (not at all) -100 (extremely) sliding scale. Responses were then averaged with higher scores indicating greater high arousal positive affect.

    Measured: within approximately 24 hours of treatment

  5. Low Arousal Positive Affect Scores

    The investigators will examine if there are differences in self-reported low arousal positive affect, as measured by a subscale of the Positive Affect-Negative Affect Schedule-X, as a function of vaccine condition. Participants indicated the extent to which they felt each of 5 low arousal positive emotions (i.e., "attentive," "calm", "interested", "grateful", "relieved") on a 0 (not at all) -100 (extremely) sliding scale. Responses were then averaged with higher scores indicating greater low arousal positive affect.

    Measured: within approximately 24 hours of treatment

  6. Sleep Quality Scores

    The investigators will examine if there are differences in self-reported sleep quality, as measured by five items adapted from the Brief Pittsburgh Sleep Quality Index, as a function of vaccine condition. The 5-item scale assess sleep duration, sleep quality, daytime dysfunction, sleep latency, and nighttime disturbances- each producing a score ranging from 0 to 3. These scores are then summed; the total range is 0-15 with higher scores indicating poorer sleep.

    Measured: within approximately 24 hours of treatment

  7. Social Disconnection Scores

    The investigators will examine if there are differences in self-reported social disconnection, as measured by a subset of items utilized in prior research (Moieni et al., 2015), as a function of vaccine condition. The 10-item scale includes Likert-type questions using a 5- point scale ranging from 1 (Not at all) to 5 (Very much so) which are then averaged; the total range is 0-5 with higher scores indicating greater feelings of social disconnection.

    Measured: within approximately 24 hours of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Dec 2022
  2. Study start17 Oct 2022
  3. Primary completion15 Dec 2023
  4. Study completion15 Dec 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Outcomes assessor
Enrolment
104 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05654441
Sponsor's protocol ID
22-1024
Other IDs
2047344
Acronym
BSB
Status last verified
Jul 2024
First submitted
8 Dec 2022
Last updated
27 Nov 2024
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).

Publications

  • Barrett LF. The theory of constructed emotion: an active inference account of interoception and categorization. Soc Cogn Affect Neurosci. 2017 Jan 1;12(1):1-23. doi: 10.1093/scan/nsw154.

    PubMed 27798257
  • SCHACHTER S, SINGER JE. Cognitive, social, and physiological determinants of emotional state. Psychol Rev. 1962 Sep;69:379-99. doi: 10.1037/h0046234. No abstract available.

    PubMed 14497895
  • Dickerson SS, Kemeny ME. Acute stressors and cortisol responses: a theoretical integration and synthesis of laboratory research. Psychol Bull. 2004 May;130(3):355-91. doi: 10.1037/0033-2909.130.3.355.

    PubMed 15122924
  • Richeson JA, Shelton JN. Negotiating Interracial Interactions: Costs, Consequences, and Possibilities. Current Directions in Psychological Science. 2007;16(6):316-320. doi:10.1111/j.1467-8721.2007.00528.x

  • Siegel EH, Sands MK, Van den Noortgate W, Condon P, Chang Y, Dy J, Quigley KS, Barrett LF. Emotion fingerprints or emotion populations? A meta-analytic investigation of autonomic features of emotion categories. Psychol Bull. 2018 Apr;144(4):343-393. doi: 10.1037/bul0000128. Epub 2018 Feb 1.

    PubMed 29389177
  • Bartz JA, Zaki J, Bolger N, Ochsner KN. Social effects of oxytocin in humans: context and person matter. Trends Cogn Sci. 2011 Jul;15(7):301-9. doi: 10.1016/j.tics.2011.05.002. Epub 2011 Jun 21.

    PubMed 21696997
  • Storbeck J, Clore GL. Affective Arousal as Information: How Affective Arousal Influences Judgments, Learning, and Memory. Soc Personal Psychol Compass. 2008 Sep 1;2(5):1824-1843. doi: 10.1111/j.1751-9004.2008.00138.x.

    PubMed 25067943
  • Eisenberger NI, Moieni M, Inagaki TK, Muscatell KA, Irwin MR. In Sickness and in Health: The Co-Regulation of Inflammation and Social Behavior. Neuropsychopharmacology. 2017 Jan;42(1):242-253. doi: 10.1038/npp.2016.141. Epub 2016 Aug 2.

    PubMed 27480575
  • Gassen J, Hill SE. Why inflammation and the activities of the immune system matter for social and personality psychology (and not only for those who study health). Soc Personal Psychol Compass. May 2019:e12471. doi:10.1111/spc3.12471

  • Kemeny ME. Psychobiological responses to social threat: evolution of a psychological model in psychoneuroimmunology. Brain Behav Immun. 2009 Jan;23(1):1-9. doi: 10.1016/j.bbi.2008.08.008. Epub 2008 Sep 10.

    PubMed 18809488
  • Hennessy MB, Deak T, Schiml PA. Sociality and sickness: have cytokines evolved to serve social functions beyond times of pathogen exposure? Brain Behav Immun. 2014 Mar;37:15-20. doi: 10.1016/j.bbi.2013.10.021. Epub 2013 Oct 31.

    PubMed 24184399
  • Dhabhar FS, Malarkey WB, Neri E, McEwen BS. Stress-induced redistribution of immune cells--from barracks to boulevards to battlefields: a tale of three hormones--Curt Richter Award winner. Psychoneuroendocrinology. 2012 Sep;37(9):1345-68. doi: 10.1016/j.psyneuen.2012.05.008. Epub 2012 Jun 22.

    PubMed 22727761
  • Leschak CJ, Eisenberger NI. Two Distinct Immune Pathways Linking Social Relationships With Health: Inflammatory and Antiviral Processes. Psychosom Med. 2019 Oct;81(8):711-719. doi: 10.1097/PSY.0000000000000685.

    PubMed 31600173
  • Slavich GM, Irwin MR. From stress to inflammation and major depressive disorder: a social signal transduction theory of depression. Psychol Bull. 2014 May;140(3):774-815. doi: 10.1037/a0035302. Epub 2014 Jan 13.

    PubMed 24417575
  • Slavich GM, Cole SW. The Emerging Field of Human Social Genomics. Clin Psychol Sci. 2013 Jul;1(3):331-348. doi: 10.1177/2167702613478594.

    PubMed 23853742

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Influenza vaccine in people with Psychology, Social and Inflammation, run by University of North Carolina, Chapel Hill at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Nov 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

IL-6 Levels 24 Hours After Vaccine (time frame: within approximately 24 hours of treatment). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05654441, which also lists 39 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Nov 2024.

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