Vitamin D and Severe Asthma Exacerbations (SAVED-P)

A Phase I Trial for Children With Vitamin D Insufficiency and High Risk of Severe Asthma Exacerbations

This study of vitamin D is designed to assess both the safety and efficacy of potential doses (2,000 IU/day and 4,000 IU/day) in raising a vitamin D level to a normal range in a short period of time (e.g. 4 weeks or less) compared to 200 IU/day.

In children with vitamin D insufficiency or deficiency who are at risk for severe asthma exacerbations, we hypothesize that both vitamin D supplementation with 4,000 IU/day and 2,000 IU/day will safely achieve normal vitamin D levels, but that the higher dose (4,000 IU/day) will result in a larger proportion of subjects achieving this level at 4 and 8 weeks.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Dietary supplement: Cholecalciferol

Detailed Description

Asthma is a major public health problem in the United States and worldwide. Severe disease exacerbations account for the majority of costs attributable to asthma in the United States. Vitamin D is an essential nutrient with significant immuno-modulatory effects. The observation that vitamin D insufficiency and asthma share risk factors such as urban residence, obesity, and African American ethnicity has generated significant interest in exploring a link between these two conditions.

This is an 8-week randomized, double-masked, controlled trial of vitamin D3 (2,000 IU/day and 4,000 IU/day) to achieve vitamin D sufficiency (a serum 25(OH)D ≥30 ng/ml in 60 school-aged children (ages 6 to 14 years) who have vitamin D insufficiency (a serum 25(OH)D <30 ng/ml) and are at risk for severe asthma exacerbations, but whose asthma that is well-controlled on medium-dose inhaled corticosteroid (ICS) at the end of a 4-week run-in period.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Children's Hospital of Pittsburgh of UPMC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 14 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Be at least 6 years of age and younger than 15 years of age
• Have physician-diagnosed asthma
• Taking a medium dose of ICS (e.g. fluticasone 220mcg BID) for daily asthma control for at least 6 months in the prior year.
• Have had a severe asthma exacerbation in the previous year, defined as an Emergency Department (ED) visit, hospitalization, or unscheduled clinic visit for asthma resulting in intramuscular, intravenous, or oral steroids.
• Have bronchodilator responsiveness (BDR, an increase in FEV1 ≥12% from baseline after administration of inhaled albuterol) or (if no BDR) increased airway responsiveness to methacholine challenge
• Have vitamin D insufficiency (a serum vitamin D (25(OH)D) level <30 ng/ml)
• Have his/her parents give voluntary written consent to participate in the study

Exclusion Criteria:

• Chronic respiratory disorder other than asthma (e.g., bronchiectasis).
• Severe asthma, as evidenced by any of the following: a) chronic need for medication other than single controller therapy and inhaled β2-agonist, b) intubation for asthma at any time, and c) ≥2 hospitalizations or ≥6 severe asthma exacerbations in the previous year
• History of cigarette smoking in the prior year or former smoking if ≥5 pack-years
• Hepatic or renal disease, metabolic rickets, malabsorptive disorders, or other chronic diseases that would affect vitamin D metabolism
• Immune deficiency, cleft palate or Down's syndrome, which might increase the child's likelihood of respiratory infections
• Treatment with anticonvulsants or pharmacological doses of vitamin D (≥1,000 IU/day of vitamin D2 or D3)
• Chronic oral corticosteroid therapy
• Inability to perform acceptable spirometry
• Use of investigational therapies or participation in clinical trials 30 days before or during the duration of the study
• Serum calcium >10.8 mg/dl
• Serum 25(OH) D <10 ng/ml (severe vitamin D deficiency)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cholecalciferol 4000 IU; Cholecalciferol 4000 IU oral chewable tablet once daily for 8 weeks	Dietary supplement: Cholecalciferol; vitamin D supplementation with either 2,000 IU/day or 4,000 IU/day compared to vitamin D3 supplementation with 200 IU/day.; Other Names: vitamin D3
Experimental: Cholecalciferol 2000 IU; Cholecalciferol 2000 IU oral chewable tablet once daily for 8 weeks	Dietary supplement: Cholecalciferol; vitamin D supplementation with either 2,000 IU/day or 4,000 IU/day compared to vitamin D3 supplementation with 200 IU/day.; Other Names: vitamin D3
Active Comparator: Cholecalciferol 200 IU; Cholecalciferol 200 IU oral chewable tablet once daily for 8 weeks	Dietary supplement: Cholecalciferol; vitamin D supplementation with either 2,000 IU/day or 4,000 IU/day compared to vitamin D3 supplementation with 200 IU/day.; Other Names: vitamin D3

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Sufficient Vitamin D Levels (≥30 ng/ml) After 8 Weeks of Supplementation	The primary outcome of the proposed trial will be a sufficient (≥30 ng/ml) vitamin D level after 8 weeks of supplementation	8 weeks
Number of Participants With Vitamin D Sufficiency (Vitamin D ≥30 ng/ml) After 4 Weeks of Supplementation	The outcome is defined as the number of participants with a sufficient (≥30 ng/ml) vitamin D level after 8 weeks of supplementation	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Vitamin D Toxicity	Participants with vitamin D toxicity, hypercalcemia (>10.8mg/dl) and/or an elevated urine Ca/Cr ratio (>0.37)	8 weeks
Number of Participants With Elevated Urinary Calcium/Creatinine Ratio	Elevated urinary calcium/creatinine ratio defined as UCa/UCr > 0.37 after either 4 weeks or 8 weeks of supplementation	4 and/or 8 weeks
Number of Participants With FEV1 < 80% of Predicted	Forced expiratory volume in 1 second (FEV1) as percent predicted (with reference values used according to the child's age, gender and ethnicity).	8 weeks

Collaborators and Investigators

• Sponsor: University of Pittsburgh
• Investigators: Principal Investigator: Juan C Celedon, M.D., Dr.P.H., University of Pittsburgh

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (Actual): January 1, 2015
• Study Completion (Actual): January 1, 2015

Study Registration Dates

• First Submitted: August 9, 2013
• First Submitted That Met QC Criteria: August 9, 2013
• First Posted (Estimate): August 13, 2013

Study Record Updates

• Last Update Posted (Actual): March 23, 2017
• Last Update Submitted That Met QC Criteria: February 2, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: asthma; vitamin D
• 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; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: SAVED-P

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO