Test if adding Vitamin D, a safe standard vitamin supplement to steroid tablets, will improve the clinical response to steroids in patients who are considered to be steroid resistant

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 40

Inclusion Criteria

1.Male or Female adults aged between 18 to 75 years.
2.Documented history and typical symptoms of asthma for = 6 months prior to screening.
3.Pre-bronchodilator FEV1 < 80% predicted and documented variability in airways obstruction of 12% or greater within the previous 5 years or diurnal Peak Flow variability of > 20%.
4.Corticosteroid refractory asthma, as defined by a < 10% improvement in FEV1 following a 14 day course of prednisolone 40mg/1.73m2/day29-31.
5.Written informed consent received.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40

Exclusion Criteria

1.Past or present disease, which, as judged by the investigator, may affect the study outcome (other than asthma, rhinitis or eczema).
2.Serum corrected calcium >2.66mmol/L
3.Clinically significant deviation from normal (physical examination or laboratory parameters) as judged by the investigator at the screening visit.
4.Current smoker or an ex-smoker of less than 5 years with a greater than 5 pack year history.
5.Pregnant or lactating females or those at risk of pregnancy (women of childbearing age may be offered a pregnancy test prior to recruitment).
6.History of a respiratory tract infection and/or exacerbation of asthma within 4 weeks of the screening visit requiring oral corticosteroid tablets.
7.Participation in a study involving an investigational medicinal product in the previous 3 months or blood donation within the last year.
8.Current or previous allergen immunotherapy.
9. Concomitant treatment with lithium carbonate or calcium supplements. Thiazide diuretics are a contraindication if the participant is taking calcium supplements at the same time.
10.Inability to understand or comply with the research protocol

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Our main objective is to investigate whether administration of 1-alpha,25-dihydroxyvitamin D3 enhances the clinical response to orally administered corticosteroids in corticosteroid refractory patients with moderate to severe asthma. The primary outcome measure will be changes in lung function (FEV1).;Secondary Objective: To determine whether there is a correlation between clinical outcome and immunological biomarkers, namely T cell production of IL-10. IL-10 has anti-inflammatory actions in asthma. We hypothesise that adding vitamin D to systemic steroid treatment enhances induction of IL-10 secreting T-cells. ;Primary end point(s): The primary outcome measure is the change in FEV1 at baseline compared to the end of the treatment period.;Timepoint(s) of evaluation of this end point: This will be assessed after unblinding of the trial, when the recruitment will officially finish.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1.level of the ex-vivo production of IL-10 and other surrogate <br>biomarkers of outcome or drug effects/process by T-cells.<br>2.Serological markers of inflammation<br>3.Fraction of nitric oxide in exhaled air<br>4.ACQ score<br>;Timepoint(s) of evaluation of this end point: These will also be assessed after unblinding of the trial, when the recruitment will officially finish.