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

• Register: EUCTR
• Last refreshed on: 10 December 2018
• Main ID: EUCTR2008-002244-42-GB
• Date of registration: 15/05/2009
• Prospective Registration: Yes
• Primary sponsor: King's College London
• Public title: 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
• Scientific title: Does 1-alpha,25-dihydroxyvitamin D3 (calcitriol) enhance corticosteroid activity in steroid refractory asthma? A randomised control trial to test whether active vitamin D can improve the clinical response to steroids in asthmatic patients. - Vitamin D and steroid resistant asthma
• Date of first enrolment: 03/07/2009
• Target sample size: 40
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-002244-42
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

United Kingdom

Contacts

• Name: Dr Alexandra Nanzer
• Affiliation: Department of Asthma, Allergy and Respiratory Medicine

• Name: Dr Alexandra Nanzer
• Affiliation: Department of Asthma, Allergy and Respiratory Medicine

Key inclusion & exclusion criteria

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



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Asthma
MedDRA version: 14.0 Level: PT Classification code 10003553 Term: Asthma System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

Intervention(s)

Trade Name: Rocaltrol Capsules 0.25mcg
Product Name: Rocaltrol Capsules
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: CALCITRIOL
CAS Number: 32222063
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 0.25mcg-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: Prednisolone
Product Name: Prednisolone
Pharmaceutical Form: Tablet
INN or Proposed INN: Prednisolone
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: up to
Concentration number: 40mg/1.73m2-

Primary Outcome(s)

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.

Timepoint(s) of evaluation of this end point: This will be assessed after unblinding of the trial, when the recruitment will officially finish.

Primary end point(s): The primary outcome measure is the change in FEV1 at baseline compared to the end of the treatment period.

Secondary Outcome(s)

Secondary end point(s): 1. level of the ex-vivo production of IL-10 and other surrogate
biomarkers of outcome or drug effects/process by T-cells.
2. Serological markers of inflammation
3. Fraction of nitric oxide in exhaled air
4. ACQ score

Timepoint(s) of evaluation of this end point: These will also be assessed after unblinding of the trial, when the recruitment will officially finish.

Secondary ID(s)

VITD1/08

Source(s) of Monetary Support

Asthma UK

Secondary Sponsor(s)

Guy's and St Thomas' NHS Foundation Trust