Clinical trial NCT01248065: Study of the Effect of Vitamin D as an Add-on Therapy to Corticosteroids in Asthma
Official title: Vitamin D Add-on Therapy Enhances Corticosteroid Responsiveness in Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Asthma
Keywords: Asthma
Vitamin D
Corticosteroids
Treatment failure
Lead sponsor: Milton S. Hershey Medical Center
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2010-11-25
Enrollment: 408
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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)

Primary outcomes:
measure: Treatment Failure
timeFrame: Twenty-eight week intervention period from randomization until end of trial.
Secondary outcomes:
measure: Lung Function Change From Baseline
timeFrame: Change is measured as value at 28 weeks minus baseline value.
measure: Exacerbations
timeFrame: Overall exacerbation rate during 28-week trial
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California - San Francisco
state: California
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center/Stroger Hospital
state: Illinois
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: St. Louis
country: United States
facility: Washington University
state: Missouri
city: Durham
country: United States
facility: Duke University School of Medicine
state: North Carolina
city: Raleigh
country: United States
facility: North Carolina Clinical Research
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Cleveland
country: United States
facility: Rainbow Babies and Children's Hospital
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Madison
country: United States
facility: University of Wisconsin-Madison
state: Wisconsin
city: Milwaukee
country: United States
facility: Aurora Sinai Medical Center
state: Wisconsin
Study officials:
affiliation: Pennsylvania State University College of Medicine
name: David T. Mauger, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Brigham and Women's Hospital
name: Elliot Israel, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Northwestern Memorial Hospital
name: Lewis Smith, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Chicago
name: Julian Solway, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Rush University Medical Center
name: James Moy, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: National Jewish Health
name: Richard Martin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Wisconsin, Madison
name: Christine Sorkness, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Aurora Sinai Medical Center
name: Elizabeth Bade, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pittsburgh Medical Center
name: Sally Wenzel, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Case Western Reserve University School of Medicine
name: James Chmiel, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Washington University School of Medicine
name: Mario Castro, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, San Francisco
name: Homer Boushey, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke University
name: Monica Kraft, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Wake Forest University Health Sciences
name: Stephen Peters, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Virginia Health System
name: W. Gerald Teague, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: North Carolina Clinical Research
name: Craig LaForce, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Emory University
name: Anne Fitzpatrick, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Illinois at Chicago
name: Jerry Krishnan, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. No abstract available.
citation: 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.