Study of the Effect of Vitamin D as an Add-on Therapy to Corticosteroids in Asthma (VIDA)

• ClinicalTrials.gov Identifier: NCT01248065
• Recruitment Status: Completed
• First Posted: November 25, 2010
• Results First Posted: August 13, 2014
• Last Update Posted: August 13, 2014
• Sponsor: Milton S. Hershey Medical Center
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Information provided by (Responsible Party): dave mauger, Milton S. Hershey Medical Center

Study Description

Brief Summary:

The purpose of the study is to find out if taking vitamin D in addition to an asthma controller medication helps to prevent worsening of asthma symptoms and asthma attacks.

Condition or disease	Intervention/treatment	Phase
Asthma	Drug: Vitamin D3; Drug: Ciclesonide	Phase 3

Detailed Description:

This is a randomized, double-blind parallel group trial that will enroll individuals who have vitamin D insufficiency and asthma with persistent symptoms despite low-dose inhaled corticosteroid. Participants on low-dose inhaled corticosteroid will be randomized to add-on therapy with either placebo or high-dose vitamin D for a 28-week period. During the inhaled corticosteroid-stable phase, participants will remain on low-dose inhaled corticosteroid. During the inhaled corticosteroid-taper phase, participants will taper their inhaled corticosteroid by 50% at two time-points post-randomization. The investigators will determine if the addition of vitamin D reduces the likelihood of treatment failure when compared to placebo during both the inhaled corticosteroid-stable and inhaled corticosteroid-taper phases of the study. Given the high prevalence of both vitamin D insufficiency and asthma, this trial has high potential to impact daily asthma management.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 408 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Vitamin D Add-on Therapy Enhances Corticosteroid Responsiveness in Asthma
• Study Start Date: April 2011
• Actual Primary Completion Date: January 2014
• Actual Study Completion Date: January 2014

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Ciclesonide + placebo	Drug: Ciclesonide; Low dose inhaled corticosteroid (80 mcg/puff two puffs twice daily); Other Name: Alvesco®
Experimental: Ciclesonide + Vitamin D	Drug: Vitamin D3; vitamin D (100,000 IU loading dose followed by 4,000 IU/day); Drug: Ciclesonide; Low dose inhaled corticosteroid (80 mcg/puff two puffs twice daily); Other Name: Alvesco®

Outcome Measures

Primary Outcome Measures :

1. Treatment Failure [ Time Frame: Twenty-eight week intervention period from randomization until end of trial. ]
   Treatment failure is a well-defined asthma outcome reflecting overall asthma control that has been used previously in multiple clinical trials. Treatment failure as defined in the current proposal and prior trials is consistent with the American Thoracic Society (ATS)/European Respiratory Society(ERS) definition of a moderate exacerbation - a deterioration in symptoms and/or lung function with increased rescue bronchodilator use that lasts 2 days or more. The percentages of participants experiencing a treatment failure are Kaplan-Meier estimates of failure rate.

Secondary Outcome Measures :

1. Lung Function Change From Baseline [ Time Frame: Change is measured as value at 28 weeks minus baseline value. ]
   FEV1 (liters) and methacholine PC20 will be evaluated. Changes are measured as 28 weeks minus baseline.
2. Exacerbations [ Time Frame: Overall exacerbation rate during 28-week trial ]
   Outcome defined as number of exacerbations per person-year.

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• Men and women 18 years of age and older
• Physician-diagnosed asthma for at least previous 12 months
• Asthma confirmed by: (a) β-agonist reversibility of forced expiratory volume in 1 second (FEV1) ≥12 % following 180 mcg (4 puffs) levalbuterol at visit 1 OR (b) methacholine provocative concentration causing a 20% fall in FEV1 (PC20) ≤ 8 mg/ml if not receiving an inhaled corticosteroid or ≤ 16 mg/ml if receiving an inhaled corticosteroid at visit 2. Source documentation for PC20 from an AsthmaNet methacholine challenge completed within 6 months of visit 2 will be accepted.
• Stable asthma controller therapy (inhaled corticosteroid or leukotriene modifier only) dose for past 2 weeks
• FEV1 ≥ 50% of predicted at visit 1
• Vitamin D level of less than 30 ng/ml at visit 0
• Experienced no more than one treatment failure in the VIDA run-in or oral corticosteroid (OCS) response periods on previous enrollments
• For women of childbearing potential: not pregnant, non-lactating, and agree to practice an adequate birth control method for the duration of the study

Exclusion Criteria:

• Taking vitamin D supplements containing > 1000 IU/day of vitamin D
• Taking >2500 mg/day calcium supplements
• Chronic oral corticosteroid therapy
• Chronic inhaled corticosteroid therapy > 1,000 mcg of fluticasone daily or the equivalent
• History of physician-diagnosed nephrolithiasis
• Use of concomitant medications that alter vitamin D metabolism - phenytoin, phenobarbital, cardiac glycosides; or absorption - orlistat, cholestyramine, colestipol; or those that interfere with study endpoints
• Impaired renal function (GFR < 30 ml/min)
• Asthma exacerbation within past 4 weeks requiring systemic corticosteroids
• Respiratory tract infection within past 4 weeks
• Chronic diseases (other than asthma)
• History of cigarette smoking within the past 1 year or > 10 pack years total
• Serum calcium greater than 10.2 mg/dl on entry
• Urine calcium/creatinine ratio greater than 0.37 (urinary Ca and Creat in mg)

Contacts and Locations

Locations

United States, California

University of California - San Francisco

San Francisco, California, United States, 94143

United States, Colorado

National Jewish Health

Denver, Colorado, United States, 80206

United States, Georgia

Emory University

Atlanta, Georgia, United States, 30322

United States, Illinois

Northwestern Memorial Hospital

Chicago, Illinois, United States, 60611

Rush University Medical Center/Stroger Hospital

Chicago, Illinois, United States, 60612

University of Illinois at Chicago

Chicago, Illinois, United States, 60612

University of Chicago

Chicago, Illinois, United States, 60637

United States, Massachusetts

Brigham and Women's Hospital

Boston, Massachusetts, United States, 02115

United States, Missouri

Washington University

St. Louis, Missouri, United States, 63110

United States, North Carolina

Duke University School of Medicine

Durham, North Carolina, United States, 27110

North Carolina Clinical Research

Raleigh, North Carolina, United States, 27607

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States, 27157

United States, Ohio

Rainbow Babies and Children's Hospital

Cleveland, Ohio, United States, 44106

United States, Pennsylvania

University of Pittsburgh

Pittsburgh, Pennsylvania, United States, 15213

United States, Wisconsin

University of Wisconsin-Madison

Madison, Wisconsin, United States, 53792

Aurora Sinai Medical Center

Milwaukee, Wisconsin, United States, 53233

Sponsors and Collaborators

Milton S. Hershey Medical Center

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: David T. Mauger, PhD; Pennsylvania State University College of Medicine
• Principal Investigator: Elliot Israel, MD; Brigham and Women's Hospital
• Principal Investigator: Lewis Smith, MD; Northwestern Memorial Hospital
• Principal Investigator: Julian Solway, MD; University of Chicago
• Principal Investigator: James Moy, MD; Rush University Medical Center
• Principal Investigator: Richard Martin, MD; National Jewish Health
• Principal Investigator: Christine Sorkness, MD; University of Wisconsin, Madison
• Principal Investigator: Elizabeth Bade, MD; Aurora Sinai Medical Center
• Principal Investigator: Sally Wenzel, MD; University of Pittsburgh Medical Center
• Principal Investigator: James Chmiel, MD; Case Western Reserve University School of Medicine
• Principal Investigator: Mario Castro, MD; Washington University School of Medicine
• Principal Investigator: Homer Boushey, MD; University of California, San Francisco
• Principal Investigator: Monica Kraft, MD; Duke University
• Principal Investigator: Stephen Peters, MD; Wake Forest University Health Sciences
• Principal Investigator: W. Gerald Teague, MD; University of Virginia Health System
• Principal Investigator: Craig LaForce, MD; North Carolina Clinical Research
• Principal Investigator: Anne Fitzpatrick, MD; Emory University
• Principal Investigator: Jerry Krishnan, MD; University of Illinois at Chicago

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Jiao J, King TS, McKenzie M, Bacharier LB, Dixon AE, Codispoti CD, Dunn RM, Grossman NL, Lugogo NL, Ramratnam SK, Traister RS, Wechsler ME, Castro M; National Heart, Lung, and Blood Institute's AsthmaNet. Vitamin D3 therapy in patients with asthma complicated by sinonasal disease: Secondary analysis of the Vitamin D Add-on Therapy Enhances Corticosteroid Responsiveness in Asthma trial. J Allergy Clin Immunol. 2016 Aug;138(2):589-592.e2. doi: 10.1016/j.jaci.2015.12.1329. Epub 2016 Mar 11.

Castro M, King TS, Kunselman SJ, Cabana MD, Denlinger L, Holguin F, Kazani SD, Moore WC, Moy J, Sorkness CA, Avila P, Bacharier LB, Bleecker E, Boushey HA, Chmiel J, Fitzpatrick AM, Gentile D, Hundal M, Israel E, Kraft M, Krishnan JA, LaForce C, Lazarus SC, Lemanske R, Lugogo N, Martin RJ, Mauger DT, Naureckas E, Peters SP, Phipatanakul W, Que LG, Sheshadri A, Smith L, Solway J, Sullivan-Vedder L, Sumino K, Wechsler ME, Wenzel S, White SR, Sutherland ER; National Heart, Lung, and Blood Institute's AsthmaNet. Effect of vitamin D3 on asthma treatment failures in adults with symptomatic asthma and lower vitamin D levels: the VIDA randomized clinical trial. JAMA. 2014 May;311(20):2083-91. doi: 10.1001/jama.2014.5052.

• Responsible Party: dave mauger, Principal Investigator, AsthmaNet Data Coordinating Center, Milton S. Hershey Medical Center
• ClinicalTrials.gov Identifier: NCT01248065
• Other Study ID Numbers: AsthmaNet 001; 1U10HL098115 ( U.S. NIH Grant/Contract )
• First Posted: November 25, 2010
• Results First Posted: August 13, 2014
• Last Update Posted: August 13, 2014
• Last Verified: July 2014

Keywords provided by dave mauger, Milton S. Hershey Medical Center:

Asthma; Vitamin D; Corticosteroids; Treatment failure

Additional relevant MeSH terms:

Asthma; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Vitamin D; Cholecalciferol; Ciclesonide; Vitamins; Micronutrients; Physiological Effects of Drugs; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Allergic Agents