A Study Evaluating Vitamin D in Allergic Bronchopulmonary Aspergillosis Complicating Asthma

Study Overview
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Brief Summary
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Allergic bronchopulmonary aspergillosis (ABPA) is a immunological pulmonary disorder caused by hypersensitive reaction to spores of Aspergillus fumigatus. The prevalence of disease is about 1-2% in asthmatics and 2-15% in patients with cystic fibrosis. The interest in ABPA stems from the fact that the disease is glucocorticoid-sensitive and early treatment can prevent progression to end-stage lung disease. Recently anti-Th2 therapies have been suggested as treatment for ABPA. Vitamin D has been shown to suppress the Th2 responses and decrease the levels of Th2 interleukins. Hence, the investigators propose to assess the role of vitamin D in treating ABPA.

Detailed Description
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Allergic bronchopulmonary aspergillosis (ABPA) is a immunological pulmonary disorder caused by hypersensitive reaction to spores of Aspergillus fumigatus. The prevalence of disease is about 1-2% in asthmatics and 2-15% in patients with cystic fibrosis. The interest in ABPA stems from the fact that the disease is glucocorticoid-sensitive and early treatment can prevent progression to end-stage lung disease. Systemic steroids remain the mainstay of treatment in ABPA. Antifungal agents are also useful as they reduce fungal load. Newer therapies like omalizumab (anti immunoglobulin E [IgE] antibody), inhalational amphotericin and Anti Th2 therapies are being studied. In pathogenesis of ABPA, there is heightened Th2 activity as a result of type 1 hypersensitive reaction to Aspergillus fumigatus and levels of Th2 cytokines like IL-3, IL-5 and IL-13 and IgE levels are increased in patients with ABPA compared with asthma patients without ABPA. Recently anti Th2 therapies have been suggested as treatment for ABPA. Vitamin D has been shown to suppress the Th2 immunity and decrease the levels of Th2 interleukins. Hence, the investigators propose to assess the role of vitamin D in treatment of ABPA.

Official Title
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A Study Evaluating Vitamin D in Allergic Bronchopulmonary Aspergillosis Complicating Asthma

Conditions
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Allergic Bronchopulmonary Aspergilloses

Intervention / Treatment
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* Drug: Glucocorticoids
* Drug: Vitamin D


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of ABPA as per the International Society for Human and Animal Mycology Working group criteria Treatment naïve Exclusion Criteria: Failure to provide informed consent Enrollment in another trial of ABPA Pregnancy Creatinine more than or equal to 1.5 mg/dL Immunosuppressive states like chronic liver disease, chronic renal failure, cytotoxic therapy, uncontrolled diabetes mellitus and others

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Glucocorticoid group<br>Oral prednisolone 0.5 mg/kg/day for four weeks, 0.25 mg/kg/day for four weeks followed by 0.125 mg/kg/day for four weeks. Prednisolone will then be tapered by 5 mg every two weeks and discontinued. The total duration of glucocorticoids will be four months | Drug: Glucocorticoids<br>* Oral prednisolone for four months<br>|
| Experimental: Vitamin D plus Glucocorticoid group<br>Oral vitamin D3 tablet, 60,000 IU weekly for 2 months (8 doses) along with Oral prednisolone 0.5 mg/kg/day for four weeks, 0.25 mg/kg/day for four weeks followed by 0.125 mg/kg/day for four weeks. Prednisolone will then be tapered by 5 mg every two weeks and discontinued. The total duration of glucocorticoids will be four months | Drug: Glucocorticoids<br>* Oral prednisolone for four months<br>Drug: Vitamin D<br>* Oral vitamin D for two months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Decline in total IgE | Total IgE at baseline and two months | Two months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Decline in total IgE | Total IgE at baseline and four months | Four months | 
| Decline in total IgE | Total IgE at baseline and six months | Six months | 
| Th1/Th2 cytokines | Th1 (IL-2 and interferon-gamma) and Th2 (IL4, IL5, IL10) cytokines at baseline and two months | Two months | 
| Th1/Th2 cytokines | Th1 (IL-2 and interferon-gamma) and Th2 (IL4, IL5, IL10) cytokines at baseline and four months | Four months | 
| Th1/Th2 cytokines | Th1 (IL-2 and interferon-gamma) and Th2 (IL4, IL5, IL10) cytokines at baseline and six months | Six months | 
| Time to first exacerbation | The time to first exacerbation will be noted in the two groups | One year |