A Study Evaluating Vitamin D in Allergic Bronchopulmonary Aspergillosis Complicating Asthma

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.

Study Overview

• Status: Completed
• Conditions: Allergic Bronchopulmonary Aspergilloses
• Intervention / Treatment: Drug: Glucocorticoids; Drug: Vitamin D

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• India
  • Chandigarh, India, 160012
    • Postgraduate Institute of Medical Education and Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Glucocorticoid group; 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; Oral prednisolone for four months
Experimental: Vitamin D plus Glucocorticoid group; 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; Oral prednisolone for four months; Drug: Vitamin D; Oral vitamin D for two months

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Postgraduate Institute of Medical Education and Research

Publications and helpful links

General Publications

• Dodamani MH, Muthu V, Thakur R, Pal A, Sehgal IS, Dhooria S, Aggarwal AN, Garg M, Chakrabarti A, Agarwal R. A randomised trial of vitamin D in acute-stage allergic bronchopulmonary aspergillosis complicating asthma. Mycoses. 2019 Apr;62(4):320-327. doi: 10.1111/myc.12879. Epub 2019 Feb 5.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2016
• Primary Completion (Actual): June 30, 2018
• Study Completion (Actual): June 30, 2018

Study Registration Dates

• First Submitted: April 21, 2017
• First Submitted That Met QC Criteria: April 27, 2017
• First Posted (Actual): April 28, 2017

Study Record Updates

• Last Update Posted (Actual): August 23, 2018
• Last Update Submitted That Met QC Criteria: August 22, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bacterial Infections and Mycoses; Respiratory Hypersensitivity; Hypersensitivity; Mycoses; Lung Diseases, Fungal; Aspergillosis; Pulmonary Aspergillosis; Aspergillosis, Allergic Bronchopulmonary; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Micronutrients; Vitamins; Bone Density Conservation Agents; Vitamin D; Glucocorticoids
• Other Study ID Numbers: Pulm.Med/2017/002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No