Meditation and Exercise for Prevention of Acute Respiratory Infection — MEPARI  

Acute Respiratory Infection Clinical Trial

Official title: Meditation and Exercise for Prevention of Acute Respiratory Infection

Status Completed

Clinical Trial Summary

The overarching goal of this project is to determine whether mind-body practices such as meditation or exercise can reduce the public health burden of acute respiratory infection. A major secondary goal is to determine whether mindfulness meditation or moderately strenuous exercise can enhance immune processes such as antibody response to influenza vaccination (flu shots). Finally, we want to investigate the influence of stress, optimism, anxiety and positive and negative emotion on immunity and resistance to respiratory infection.

Clinical Trial Description

ABSTRACT

Background Preliminary evidence suggests that meditation and exercise may work through interacting psychological and physiological pathways to influence the immune system and reduce infectious respiratory disease.

Methods In this study, women and men aged 50 and older will be randomized to: 1) an 8-week behavioral training program in mindfulness meditation, 2) an intensity, duration and location-matched 8-week exercise training program, or 3) a waiting list control group. Sample size will be N=150 enrolled, with N=50 in each group. The main patient-oriented outcome will be severity-adjusted total days of acute respiratory infection (ARI) illness, as self-reported on the Wisconsin Upper Respiratory Symptom Survey (WURSS-24), a validated questionnaire outcome measure. Nucleic acid based viral identification will verify all symptomatic infections, and the cytokine IL-8 and nasal neutrophil from nasal wash will serve as biomarkers of illness severity. Biomarkers of immune function will include antibody response to influenza immunization (serum IgG, mucosal IgA) and cytokines IFN-γ and IL-10 from cultured ex vivo lymphocytes. Questionnaire measures assessing perceived stress, positive and negative emotion, optimism, and anxiety will be analyzed as potential mediators of immunomodulation and illness prevention.

Timeframe / logistics This will be a 2-year project, with 2 cohorts conducted during a single cold season. The first cohort of N=60 will be randomized and begin interventions in September 2009. The second cohort of N=90 will be randomized and begin interventions in January 2010. Tri-valent influenza vaccination will occur on week 6 of behavioral interventions in both cohorts. Blood for antibody titer and ex vivo cytokine assay will be drawn at baseline, at the end of the 8-week session, and once again 3 months later. Nasal swab for IgA will be done at the same times. Participants will be followed with telephone contact every 2 weeks, with monthly questionnaire instruments, and with daily self-assessments during ARI illness episodes.

Analysis ANOVA-based models will assess effects of meditation and exercise on immune markers and ARI illness. Psychological measures will be assessed as potential mediators of effects of meditation and exercise on ARI illness. Generalized estimating equations, random-effects pattern-mixture models, and hierarchical linear models will be used to assess longitudinal effects, interactions, and covariate mediation.

Section 2. Specific Aims

2.1. Background Acute respiratory infection (ARI) is a leading cause of morbidity and mortality. Influenza is the most pathogenic of the many viruses involved, and hence merits special attention. Protective and ameliorative immune mechanisms are poorly understood, but are associated with various indicators of mental as well as physical health.

A broad literature suggests that regular exercise affects the immune system, positively influences mental health, and protects against ARI illness. A separate and smaller body of evidence suggests that mindfulness meditation may lead to lower stress levels and better mental and physical health. Published evidence from our own study suggests that meditation may enhance antibody (serum IgG) response to influenza vaccination (flu shot) [1].

2.2. Methods & Aims The proposed randomized controlled trial (RCT) will test for effects of meditation and exercise on incidence and severity of ARI illness during an 8-month observation period. Participants (N=150) will be randomized to 1) an 8-week training program in mindfulness meditation, 2)an attention, duration and location-matched program in moderate intensity exercise, or 3) a waiting list control group. Each ARI illness episode will be assessed by a validated questionnaire outcomes instrument, verified with nucleic acid based multiplex viral identification system, and assessed for inflammation with IL-8 assay and neutrophil count from nasal wash. Immunological measures will include antibody response to flu shot (both serum IgG and mucosal IgA) and cytokine indicators of TH1 (IFN-γ) and TH2 (IL-10) immune response, as measured in stimulated ex vivo lymphocyte cell culture. Psychological domains to be assessed include perceived stress, positive and negative emotion, anxiety, and optimism. Immune biomarkers and psychological domains will be assessed as consequences of behavioral interventions, and as predictors of ARI illness. Finally, we will attempt to disentangle the mediating effects of psychological health on immune mechanisms and ARI illness. For example, one hypothesis is that meditation influences the immune system through reduction of stress-related immune dampening mechanisms. That hypothesis would receive support if perceived stress and ARI illness were lowest in the meditation group, and if perceived stress associated more strongly with immune biomarkers and ARI measures than did measures of other psychological domains. We expect that both exercise and meditation will improve psychological health, influence immune biomarkers, and reduce ARI illness burden. However, current evidence is not sufficient to estimate the relative magnitude of these effects, nor to confidently predict whether cellular and/or antibody-mediated immune mechanisms will be implicated.

2.3 Null hypotheses - 2.3.1 Compared to control, an 8-week training program in mindfulness meditation will not lead to statistically significant reductions in number of severity-weighted days of ARI illness. 2.3.2 Compared to control, a matched 8-week exercise training program will not lead to significant reductions in ARI illness. 2.3.3 Meditation training will not enhance either antibody response to flu shot (serum IgG, mucosal IgA), or cytokine expression linked to TH1 and TH2 cell-mediated immune pathways (IFN-γ, IL-10). 2.3.4 Exercise training will not enhance either antibody response to flu shot or cytokine expression from cultured lymphocytes. 2.3.5 Mindfulness meditation training will not lead to improvements in measures of psychological health (perceived stress, positive and negative emotion/affectivity, anxiety, optimism). 2.3.6 Exercise training will not improve these psychological measures. 2.3.7 Immune biomarkers will not predict ARI outcomes. 2.3.8 Psychological measures will not predict ARI outcomes. 2.3.9 The effects of meditation and exercise on psychological measures, immune biomarkers, and ARI illness will not be distinguishable from each other. 2.3.10 Observed effects of meditation and exercise on ARI outcomes will not be explained by either psychological measures or biomarkers of immune mechanisms.

2.4 Justification Influenza and other acute viral infections are responsible for tremendous health burden. Antibody-mediated immunity, responding to vaccination or natural exposure, is only partially effective in conferring protection. Current evidence suggests that cell-mediated immune mechanisms are important in this process. Both antibody-mediated and cell-mediated immune mechanisms have been linked to psychological domains, and appear to decline with aging. Preliminary evidence suggests that both mindfulness meditation and moderate intensity exercise may be at least partially effective in modifying immune response and reducing infectious illness burden. No studies have compared these 2 quite different behavioral intervention techniques. This proposed research would provide new knowledge regarding effects of meditation and exercise training on ARI illness, and immunological and psychological pathways involved. ;

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Acute Respiratory Infection
• Communicable Diseases
• Infection
• Respiratory Tract Infections

• NCT number: NCT01057771
• Study type: Interventional
• Source: University of Wisconsin, Madison
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: June 2009
• Completion date: June 2010