A Study to Investigate the Effect of Vitamin D3 Supplementation on Asthma Symptoms in Adults With Asthma (VITDAS)
Condition: Asthma; Vitamin D Deficiency; Nutritional Deficiency; Inflammation
MeSH terms: Asthma; Vitamin D Deficiency; Malnutrition; Inflammation
Study type: Interventional

Summary: 
      Asthma is a disease characterised by chronic inflammation of the airways leading to symptoms
      including periods of shortness of breath, wheezing and a tight chest due to airway narrowing
      in affected patients. Current data show that one in 12 adults are currently receiving
      treatment for asthma in the United Kingdom (UK), with the UK having some of the highest rates
      in Europe. In the winter, 30-40% of the UK population are vitamin D deficient with some
      asthma patients having significantly lower vitamin D levels compared to normal patients.
      Vitamin D has been shown to be involved in the development of immune-related disorders
      including asthma. Cross-sectional research has shown that reduced vitamin D levels are
      associated with reduced lung function, increased airway hyper-responsiveness and reduced
      response to glucocorticoids, suggesting vitamin D levels may also implicate asthma treatment.
      To date, there have been three randomised controlled trials (RCT) assessing the effect of
      vitamin D supplementation in adults with symptomatic asthma. These trials have not found a
      significant effect of vitamin D supplementation on asthma. However, these studies relied on
      high doses of vitamin D with long time periods between doses. There is a requirement for RCTs
      in adults with daily supplementation of lower doses of vitamin D as it has been suggested
      that daily supplementation is more effective for inducing non-classical actions of vitamin D.
      However, vitamin D has been found to significantly improve airway function as measured by
      forced expiratory volume in one second (FEV1) in adults supplemented with 100, 000
      international units (IU) vitamin D intramuscularly plus 50, 000 IU oral vitamin D weekly.
      Therefore, the effect of daily dosing on lung function also requires investigation.
      Furthermore, these trials have focussed on clinical outcomes without investigating the
      cellular mechanisms affording protection.
    

Detailed description: 
      Recruitment and sampling strategy:

      Participants will be recruited from the University of Chester (staff and students) and
      surrounding areas, United Kingdom (UK) only. Emails, posters and social media will be used to
      advertise the study to the target group (adults with asthma). A total of 28 adults with
      asthma aged 18-65 years old will be included in the study based on criteria described below.
      Eligibility will be based upon previous diagnosis of asthma by a general practitioner (GP)
      and the number of times asthma medication is required at screening before the start of the
      study. Participants will be required to complete a screening questionnaire which will provide
      information about participant's health status, drugs/medication/supplement usage and sun
      exposure. Those that have had asthma diagnosed by a GP and require their medication more than
      twice per week will be included. All eligible participants will be briefed on the study
      protocol before the beginning of the study, and the eligible participants will be given a
      participant information sheet (PIS) and asked to provide written informed consent.

      A 12 week, double blind, randomised controlled trial will be carried out in the clinical
      laboratory at The University of Chester, UK. Most vitamin D and asthma studies have used
      supplement concentrations up to 120, 000 international units (IU) with no adverse effects.
      The European Food Standards Agency (EFSA) set a no-observed-adverse-effect-level (NOAEL) of
      10,000IU/day (COT, 2015).

      Participants will be randomly allocated to 2 groups:

        1. vitamin D group

        2. placebo group

      Participants assigned to the vitamin D group will consume one capsule containing 5000 IU
      vitamin D every day. Participants in the placebo group will take an identical capsule
      containing inert filler. Participants will be asked to maintain their dietary habits and
      physical activity. The remaining supplements will be returned at the final clinic (week 12)
      and compliance will be estimated.

      Participants will be required to attend three clinics in total over a period of 12 weeks, and
      they will be assessed at baseline (Day 0), interim (Week 6) and post-intervention (Week 12).
      At each clinic, a 30ml blood sample will be taken and both height and weight will be
      measured. Before the start and end of the study, participants will be required to keep a
      3-day food diary which includes two weekdays and one weekend day to represent the habitual
      dietary intake of the participants. At each clinic, participants will complete spirometry to
      measure forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) to
      assess lung function and complete the Asthma Control Test™ (ACT) to assess asthma symptoms.
      Blood samples will be analysed on collection for a total blood cell count. Blood samples will
      be centrifuged to remove plasma. Plasma samples will be batch analysed at the end of the
      intervention to assess biomarkers of vitamin D metabolism and inflammation.

      Sample size and justification:

      Sample size was estimated using vitamin D supplementation data from a study in which FEV1
      post intervention at 6 months (mean ± standard deviation (S.D)) of 51.6 ± 9.4 L (vitamin D
      treatment group) and 31.9 ± 7.6 L (placebo group) was reported in chronic obstructive
      pulmonary disease patients receiving 100, 000 IU vitamin D each month. With an effect size of
      1.8493555, the total sample size required for each group in the proposed study is 9. Taking
      into account a 20% drop out rate, and this study lasting only 12 weeks, the total sample size
      required is 14 (power = 0.9). Therefore, the total sample size needed for the whole study is
      28. Sample size was estimated using G Power Software.

      Statistical Analysis:

      All statistical analyses will be conducted with the International Business Machines (IBM)
      Statistical Package for the Social Sciences (SPSS) Statistic Data Editor Software (version
      25). Assuming the data is normally distributed after performing a Shapiro Wilks normality
      test, a mixed model analysis of variance (ANOVA) with t-test post-hoc analysis will be
      conducted to compare the mean differences for all measured parameters between the groups at
      the different time points. A non-parametric approach will be adopted if the data is not
      normally distributed for all analyses. Differences will be considered significant with a p
      value ≤ 0.05.
    

Intervention name(s): Vitamin D3; Placebo
Intervention type(s): Dietary Supplement; Other
Intervention description(s): 5000 IU (125 μg) vitamin D3 capsules daily over 12 weeks (84 days); Inert filler capsules daily over 12 weeks (84 days)
Other intervention name(s): Cholecalciferol; Non active ingredient
Intervention MeSH terms: Vitamin D; Cholecalciferol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: Vitamin D; Asthma; Lung function; Inflammation