Vitamin D for the Treatment of Severe Asthma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00712205
Recruitment Status : Unknown
Verified August 2009 by Kantonsspital Baselland Bruderholz.
Recruitment status was:  Enrolling by invitation
First Posted : July 9, 2008
Last Update Posted : August 13, 2009
University Hospital, Basel, Switzerland
Information provided by:
Kantonsspital Baselland Bruderholz

Brief Summary:
The investigators want to test the hypothesis, that vitamin D3 improves pulmonary function and quality of life in patients with asthma relatively resistant to glucocorticoids.

Condition or disease Intervention/treatment Phase
Asthma Drug: Placebo Drug: Calcitriol Phase 4

Detailed Description:

Glucocorticoids are the first-line antiinflammatory treatment for asthma. Their multiple inhibitory properties, including the inhibition of Th2 cytokine synthesis, are likely to contribute to clinical efficacy. Glucocorticoids also enhance IL-10 production in vitro by human CD4+ and CD8+ T cells, and glucocorticoid treatment induces the synthesis of IL-10 by airway cells in asthmatic patients. IL-10 is a potent antiinflammatory and immunosuppressive leading to profound inhibition of Th1 cell-mediated immunity. A proportion of asthmatic patients fails to benefit from oral glucocorticoid therapy and are thus denoted as having glucocorticoid-resistant (SR, derived from "steroid resistant") or insensitive asthma. It has been demonstrated that CD4+ T cells from SR asthma patients fail to induce IL-10 synthesis following in vitro stimulation in the presence of dexamethasone as compared with their glucocorticoid-sensitive counterparts (SS, derived from "steroid sensitive"), suggesting a link between induction of IL-10 synthesis and clinical efficacy of glucocorticoids. One potential source of IL-10 is Tregs, which control the function of effector T cells. Glucocorticoids enhance the production of IL-10 by polyclonally stimulated T cells and these cells inhibit IFN- production by human CD4+ T cells in an IL-10-dependent manner. In both mouse and human a combination of dexamethasone and calcitriol, the active form of vitamin D3, induced high numbers of IL-10-producing T cells that made negligible amounts of Th1 and Th2 cytokines.

Xystrakis et al. (57) showed that IL-10-secreting Tregs inhibit cytokine production by previously activated allergen-specific Th2 cells and that pretreating T cells with IL-10 or adding vitamin D3 to the cell cultures can reverse the defect and enhance IL-10 production by Tregs from asthmatic patients who were resistant to glucocorticoid therapy. These manipulations increase IL-10 production to levels comparable to those observed in patients who do respond well to therapy. IL-10 increases glucocorticoid receptor expression, and the authors proposed that this is the mechanism by which IL-10 overcomes the glucocorticoid-resistant patient defect in IL-10 synthesis. This strongly suggests that vitamin D3 could potentially increase the therapeutic response to glucocorticoids in SR patients.

We want to test the hypothesis, that vitamin D3 improves pulmonary function and quality of life in patients with asthma relatively resistant to glucocorticoids.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Asthma and Vitamin D (a Clinical Pilot Study)
Study Start Date : August 2008
Estimated Primary Completion Date : August 2010
Estimated Study Completion Date : August 2010

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma Vitamin D

Arm Intervention/treatment
Placebo Comparator: A
20 Patients with asthma in a crossover design
Drug: Placebo
once daily 1mcg Placebo for 28days followed by crossover treatment

Active Comparator: B
20 Patients with asthma in a crossover design
Drug: Placebo
once daily 1mcg Placebo for 28days followed by crossover treatment

Drug: Calcitriol
once daily 1mcg Calcitriol / Placebo for 28days followed by crossover treatment

Primary Outcome Measures :
  1. the area under the 12-hour serial FEV1 curve relative to day-1 baseline (FEV1 AUCbl) and bronchial responsiveness to methacholine [ Time Frame: 4 weeks ]

Secondary Outcome Measures :
  1. daily morning and evening PEF, daily patient-rated asthma symptom scores, short-acting betamimetics use, nighttime awakenings due to asthma requiring short-acting betamimetics use and the fraction of the exhaled nitric oxide (FENO). [ Time Frame: daily ]

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 20 outpatients of either sex,
  • ages ≥18 years, with a history of persistent asthma as defined by the American Thoracic Society (ATS) will be eligible for entry into the study.
  • Additionally, patients must have been previously treated with ICS for at least 4 weeks at a stable dose equivalent to ≥400 ug/day beclomethasone dipropionate.
  • Patients will be required to have a forced expiratory volume in 1 s (FEV1) between 40-85% of predicted normal before the use of an inhaled bronchodilator and to demonstrate at least one of the following:

    • an improvement in FEV1 ≥ 12% and ≥ 200 ml within 15-30 min after inhalation of salbutamol 200-400 ug;
    • airway hyperresponsiveness to methacholine causing a 20% decline in FEV1 (PC20 FEV1) at a concentration of < 16 mg/ml;
    • diurnal peak expiratory flow (PEF) variability of ≥ 15% during at least 3 of 7 days before randomization.

Exclusion Criteria:

  • Patients with either an exacerbation of asthma or respiratory tract infection within 6 weeks or admission to a hospital for asthma within 6 weeks before the study will be excluded.
  • Also patients will not be eligible if they had > 3 nights with awakenings due to asthma that required treatment with short-acting betamimetics or had 3 days when they required > or = 12 puffs/d short-acting betamimetics during the 7days before the randomization visits.
  • Patients will also excluded if they use medications greater potency than inhaled steroid, e.g.not leukotriene inhibitors or anti-IgE (Xolair®).
  • Patients with chronic obstructive pulmonary disease and current or former smokers of >10 pack-years

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00712205

Department of Medicine
Bruderholz, Baselland, Switzerland, 4101
Sponsors and Collaborators
Kantonsspital Baselland Bruderholz
University Hospital, Basel, Switzerland
Principal Investigator: Albrecht Breitenbuecher, MD Kantonsspital Baselland Bruderholz

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Albrecht Breitenbücher MD, Department of Medicine Identifier: NCT00712205     History of Changes
Other Study ID Numbers: KSBH-336-06
First Posted: July 9, 2008    Key Record Dates
Last Update Posted: August 13, 2009
Last Verified: August 2009

Keywords provided by Kantonsspital Baselland Bruderholz:
Vitamin D

Additional relevant MeSH terms:
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Immune System Diseases
Vitamin D
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents
Calcium Channel Agonists
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Vasoconstrictor Agents