Vitamin D Regulates the Expression of Glucocorticoid Receptors in Blood of Severe Asthmatic Patients (VitaminD)

Vitamin D (VitD) deficiency is a significant public health concern in many areas around the globe which has been associated with many immune-mediated diseases, including asthma. Severe asthma has been linked with a decreased glucocorticoid receptors (GR) ratio (GR-α/ GR-β ratio), indicating steroid hyporesponsiveness. Using combined in silico and in vivo approaches, aimed to explore the immunomodulatory effect of VitD on asthmatic patients diagnosed with hypovitaminosis D.

Study Overview

• Status: Completed
• Conditions: Effect of Drug
• Intervention / Treatment: Drug: Vitamin D; Other: Placebo

Detailed Description

Vitamin D (VitD) deficiency is a significant public health concern in many areas around the globe which has been associated with many immune-mediated diseases, including asthma. Severe asthma has been linked with a decreased glucocorticoid receptors (GR) ratio (GR-α/ GR-β ratio), indicating steroid hyporesponsiveness. Using combined in silico and in vivo approaches, the investigators aimed to explore the immunomodulatory effect of VitD on asthmatic patients diagnosed with hypovitaminosis D. Methods: In silico tools were used to identify the regulatory effect of VitD supplementation on GR genes. The investigators measured the expression levels of GR-α and the inactive isoform, GR-β, in the blood of adult asthmatics diagnosed with hypovitaminosis D before and after VitD supplementation. Moreover, the blood levels of inflammatory cytokines associated with asthma severity were determined.

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of asthma
• age group between 18 and 65 years
• low level of 25-hydroxyvitamin D3 (25 D3) level less than 20ng/mL

Exclusion Criteria:

• smoker patients
• less than 18 years old
• patient on Vitamin D supplementation already

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Asthmatic low vitamin D on treatment; asthmatic patient low vitamin D level received treatment for Vitamin D 50000IU weekly	Drug: Vitamin D; A double-blinded, randomized, placebo-controlled study of VitD supplementation on 45 asthmatics with VitD deficiency was performed. Moderate to severe asthmatics between 18 and 65 years of age who had clinician-diagnosed asthma with 25-hydroxyvitamin D3 (25 D3) level less than 20ng/mL at the screening visit were recruited at the Rashid Hospital, Dubai, U.A.E., and the Zayed Military Hospital, Abu Dhabi, U.A.E. Subjects were excluded if they had used any previous VitD supplementation, had any other respiratory diseases or co-morbid conditions or were smokers. According to the American Academy of Family Physicians guidelines, participants received 50, 000 IU of VitD orally or placebo weekly over 8 weeks. Subjects were blinded to treatment and allocated to receive a VitD dose or placebo by the randomization schedule.
Placebo Comparator: Asthmatic low vitamin D on placepo; asthmatic patient low vitamin D level received placepo	Other: Placebo; A double-blinded, randomized, placebo-controlled study of VitD supplementation on 45 asthmatics with VitD deficiency was performed. Moderate to severe asthmatics between 18 and 65 years of age who had clinician-diagnosed asthma with 25-hydroxyvitamin D3 (25 D3) level less than 20ng/mL at the screening visit were recruited at the Rashid Hospital, Dubai, U.A.E., and the Zayed Military Hospital, Abu Dhabi, U.A.E. Subjects were excluded if they had used any previous VitD supplementation, had any other respiratory diseases or co-morbid conditions or were smokers. According to the American Academy of Family Physicians guidelines, participants received 50, 000 IU of VitD orally or placebo weekly over 8 weeks. Subjects were blinded to treatment and allocated to receive a VitD dose or placebo by the randomization schedule.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The top Vitamin D regulated pathways in response to Steroids by using Comparative Toxicogenomics Database from thousands of experiments.	identify VitD targeted enriched pathways, we analyzed Comparative Toxicogenomics .Enriched Ontology Clustering for the identified genes was performed using the Metascape (a web-based tool used for comprehensive gene list annotation and analysis resource)Database from thousands of experiments.	8 weeks
Asthma Severity effects on VDR and steroid receptors genes by inalyzing expression profile of publicly available datasets (GSE69683) which has a large number of participants and detailed clinical information.	analyze the expression profile of publicly available datasets (GSE69683) which has a large number of participants and detailed clinical information.	8 weeks
Examine the up-regulation of GR-α receptor by using supplementation of vitamin D on 45 vitamin D deficient asthmatics	by doing double-blinded, randomized, placebo-controlled study was performed to test the effect of VitD supplementation on 45 vitamin D deficient asthmatics.Standard statistical t-tests and one-way ANOVA were performed to test for statistical significance between data groups using GraphPad Prism 8 (GraphPad, San Diego, CA, USA). p < 0.05 was considered significant.	8 weeks
Effects of IL-17 and IL-4 cytokines in asthmatic patients while using Vitamin D supplementation by using ELISA assay	by doing double-blinded, randomized, placebo-controlled study was performed to test the effect of VitD supplementation on 45 vitamin D deficient asthmatics. Using qRT-PCR expression of the cytokines	8 weeks
Effects of IL-17 and IL-4 cytokines in asthmatic patients while using Vitamin D supplementation by using ELISA assay	by doing double-blinded, randomized, placebo-controlled study was performed to test the effect of VitD supplementation on 45 vitamin D deficient asthmatics.using Bioplex multiplex immunoassay (BioRad, CA,USA) was used to assess the protein expression of the cytokines and by measuring fold change.	8 weeks

Collaborators and Investigators

• Sponsor: Dubai Health Authority
• Collaborators: McGill University

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2012
• Primary Completion (Actual): April 30, 2014
• Study Completion (Actual): December 31, 2014

Study Registration Dates

• First Submitted: June 12, 2020
• First Submitted That Met QC Criteria: June 19, 2020
• First Posted (Actual): June 23, 2020

Study Record Updates

• Last Update Posted (Actual): June 23, 2020
• Last Update Submitted That Met QC Criteria: June 19, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Vitamin D
• Other Study ID Numbers: MRC-04/2012_06

Drug and device information, study documents

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