Mood and Influenza Vaccine Response: A Feasibility Trial

Study Overview
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Brief Summary
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This study is a 2-arm, parallel, randomised controlled feasibility trial of a brief video intervention designed to induce positive affect (mood) in older adults in primary care settings prior to the receipt of influenza vaccination. Participants will be randomised into two conditions: experimental and active control. In the experimental condition, participants will view the approximately 15 minute long intervention video immediately prior to vaccination. In the active control condition, participants will view a matched video that is designed to be mood neutral. Pre-and-post positive affect levels will be assessed by self-report questionnaires. Immune response to the intervention and vaccination responses will be assessed in saliva and serum samples respectively. The objectives of the study are to assess the impact of the intervention on mood, immune function, and antibody response to influenza vaccination in older adults. This feasibility trial will also allow data collection on exploring recruitment, attrition, intervention engagement, and practicality of collecting clinical data available through electronic records to inform the design of a future definitive trial.

Detailed Description
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The Centers for Disease Control (CDC) describe vaccinations as among the 10 most significant health achievements ever documented; and for many conditions they have been an unmitigated success (e.g., smallpox). There are, however, several populations in whom vaccine effectiveness is far from optimal. These populations are typically contending with underlying immune impairment by virtue of their advancing age and/or the presence of co-existing diseases (e.g., cancer). As a consequence, vaccines are most likely to fail those whom they most seek to benefit: individuals at the greatest risk of ill health. This has prompted research into treatments that enhance immune function prior to vaccination, so called vaccine adjuvants. The aim of such treatments is to optimise the response the immune system makes to the vaccine antigens and, in so doing, increase the likelihood that the vaccine confers protection. One area in which there has been interest is in the potential for developing psycho-behavioural vaccine adjuvants. There is considerable evidence that psychological and behavioural factors can modulate immunity; with diet, physical activity, stress, affect, sleep and social support all associated with immune response. The investigators recently conducted a longitudinal observational cohort study of multiple psychological (positive affect, negative affect, stress) and behavioural (physical activity, sleep, diet) influences on short and long-term antibody responses to influenza vaccination in older adults. This identified positive affect as the most influential psycho-behavioural factor on influenza-specific antibody responses, independently predicting both short and long-term antibody responses in the weakest immunogenic strain above and beyond known demographic and clinical determinants. Intriguingly, the investigators also observed preliminary evidence that positive affect on the day of vaccination was more predictive of antibody responses following vaccination than mood measured over the longer period surrounding vaccination. As influenza-specific antibodies are a well-established correlate of protection from serologically and clinically diagnosed influenza incidence, these data suggest that increasing positive affect immediately prior to vaccination could be used as a non-pharmacological vaccine adjuvant. Through a series of systematic steps, including focus groups and interviews with older adults and health care professionals, the investigators have recently developed a brief, positive affect intervention - designed to improve short-term mood in older adults and be deliverable within primary care. It is hoped this could act as a psycho-behavioural adjuvant to enhance poor responses to influenza vaccination in older adults. Before performing a definitive trial of the intervention's effectiveness, a feasibility trial is needed for number of reasons: To assess whether our intervention can enhance positive affect (mood) To collect information regarding likely recruitment, effect sizes, and attrition rates for informing the necessary size of a larger definitive trial To examine the practicality and acceptability of delivering the intervention in routine primary care settings To explore the feasibility of obtaining outcome data on healthcare usage for a large scale trial (hospitalisation, GP visits for flu-like symptoms from medical records) In line with the above, the investigators will be conducting a 2-arm, parallel, randomised controlled feasibility trial of a brief video intervention designed to induce positive affect (mood) in older adults in primary care settings prior to the receipt of influenza vaccination. Participants will be randomised into two conditions: experimental and active control. In the experimental condition, participants will view the approximately 15 minute long intervention video immediately prior to vaccination. In the active control condition, participants will view a matched video that is designed to be mood neutral. Pre-and-post positive affect levels will be assessed by self-report questionnaires. Immune response to the intervention and vaccination responses will be assessed in saliva (pre/post intervention) and serum samples (pre/4 weeks post-vaccination/16weeks post-vaccination) respectively.

Official Title
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A Feasibility Trial of a Brief Positive Affect Intervention to Improve the Effectiveness of Influenza Vaccine Response in Older Adults.

Conditions
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Vaccination; Infection

Intervention / Treatment
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* Other: Positive Affect Intervention
* Other: Neutral Control Intervention
* Biological: Northern Hemisphere Influenza Vaccine 2017/18 (Delivered as part of Standard Care)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and Females aged 65-85 years (inclusive) Received influenza vaccination for the 2016/17 season Eligible to receive 2017/18 influenza vaccination as part of usual care Ability to give informed consent Exclusion Criteria: Males and Females aged less than 65 or over 85 years (exclusive) Did not receive influenza vaccination for the 2016/17 season Ineligible to receive 2017/18 influenza vaccination as part of usual care Unable to provide informed consent Deemed by health care provider to be: Too physically frail to participate Diagnosed with dementia or other cognitive condition which would make participation difficult Insufficient command of English language Influenza vaccination contraindicated Sufficiently impaired of hearing or vision that exposure to the intervention or control video content as intended would be compromised Those for whom the collection of blood samples is contraindicated.

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental<br>Participants in the experimental condition will view a video designed to induce positive affect. This includes 3 short comedy clips (fork handles sketch, the two Ronnie's; A room with a view - faulty towers; Tim Vine Live stand-up extract), uplifting music (Jailhouse Rock - Elvis Presley; Happy Together - The Turtles), jokes and positive imagery. The content of the intervention has been informed by patient and public involvement, focus groups with older adults, and pilot testing. | Other: Positive Affect Intervention<br>* See Previous Description<br>Biological: Northern Hemisphere Influenza Vaccine 2017/18 (Delivered as part of Standard Care)<br>* Northern Hemisphere Influenza Vaccine 2017/18 (Delivered as part of Standard Care)<br>|
| Active Comparator: Active Control<br>Participants in the control condition will view a video of matched length to the experimental condition video, but not designed to induce mood change. This includes short documentary clips (a pride in pencils; model railways, lecture extract on hydration), neutral music and images. | Other: Neutral Control Intervention<br>* See Previous Description<br>Biological: Northern Hemisphere Influenza Vaccine 2017/18 (Delivered as part of Standard Care)<br>* Northern Hemisphere Influenza Vaccine 2017/18 (Delivered as part of Standard Care)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mood Outcome Scores [Multiple] | Affective Slider (Betella & Verschure, 2016), consists of two single item visual analogue scales. Scores for each are presented as a value from 0 to 100 with higher scores indicating greater pleasure (VAS-Valence) and arousal (VAS-Arousal). Positive and Negative Affect Schedule (Watson et al., 1988). Positive and negative affect subscales were created by summing the scores of positive and negative adjectives respectively. For each sub scale, minimum score = 10, maximum score = 50 with higher scores indicating greater positive and negative affect respectively. Pictorial scale of positive affect (unvalidated, internally developed). Participants completed a single-item photo-based measure of positive affect tailored for older adults. Participants were presented with six groups of images depicting varying degrees of positive affect, and indicate which best reflected how they felt at that moment. Minumum score 1, maximum score 6, higher scores indicate greater positive affect. | Baseline, Immediately Post Intervention (i.e, 15 minutes post-baseline). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recruitment | Recruitment rates to inform a future definitive trial | Baseline | 
| Attrition | Attrition - to inform a future definitive trial | 4 weeks (post-vaccination), 16 Weeks (post-vaccination) | 
| Secretory IgA Response | Secretory IgA levels measured in saliva samples via ELISA. This is a non-specific measure of immunological response | Baseline, Immediately Post Intervention (i.e, 15 minutes post-baseline). | 
| Vaccine Specific IgG Response | IgG levels against the 4 vaccine strains measured via ELISA. Values represent equivalent ug/ml based on diluted sample absorbance value interpolation against a standard IgG curve, multiplied by the serum dilution score (i.e., 4000). | 4 weeks (post-vaccination), 16 Weeks (post-vaccination) | 
| Health Care Utilization | Via medical records, we assessed health care usage potentially attributable to flu-like symptoms (e.g., GP visits, hospitalisation, antibiotic prescription) during the 6 months post-vaccination | Baseline to 6 months post-vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Positive Affect, Positive Mood, Influenza Vaccination, Vaccination, Randomised Controlled Trial