Effect of Vitamin D as add-on Therapy for Vitamin D Insufficient Patients With Severe Asthma

Asthma Clinical Trial

— EVITA  

Official title:

EVITA Trial: Effect of VItamin D as add-on Therapy for Vitamin D Insufficient Patients With Severe Asthma: a Randomized, Double-blind, Placebo-controlled Trial

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02424552
• Other study ID #: 2014-003
• Secondary ID: 2014-002363-15
• Status: Terminated
• Phase: Phase 4
• First received: April 14, 2015
• Last updated: April 28, 2017
• Start date: June 26, 2015
• Est. completion date: March 9, 2017

Study information

• Verified date: April 2017
• Source: Johannes Gutenberg University Mainz
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the EVITA trial is to compare the effects of vitamin D therapy with placebo on reducing the dose of inhaled or oral corticosteroids in patients with severe asthma and vitamin D insufficiency.

Description:

Patients with severe asthma represent the greatest unmet medical need among the asthmatic population, in particular due to their high risk of severe exacerbations. A substantial proportion of these patients does not achieve asthma control despite even high-dose ICS and LABA treatment, necessitating add-on therapy. For these patients oral corticosteroids (OCS) are a preferred treatment modality, which will inevitably lead to severe side effects. A high Proportion of patients with severe Asthma are Vitamin D insufficient (< 30 ng/ml). It is therefore tempting to speculate that vitamin D substitution in vitamin D insufficient patients who continue to experience suboptimal asthma control on ICS and LABA or ICS/LABA plus OCS treatment may boost corticosteroid responsiveness, thereby potentially reducing corticosteroid dose requirements and improving key parameters of asthma control.

The present study is a multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of treatment with vitamin D at a dose of 4000 IU/day administered daily following a single loading dose of 100 000 IU upon study entry over a period of 24 weeks in patients with severe asthma and vitamin D insufficiency. During the study, all patients will remain on their existing maintenance asthma therapy throughout the study, in addition to the study treatment, while reducing inhaled or oral steroids according to study protocol. The study consists of a 2-week run-in period, a 24 week double-blind treatment period including a 12 week steroid stable phase and two steroid reduction phases, followed by a follow-up visit 4 weeks after last study medication intake. The active treatment arm in this study will be standard of care plus vitamin D (loading dose of 100 000 IU upon study entry, to be followed by 4000 IU/day for the rest of the study period) while the comparator arm will be standard of care plus placebo.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 54
• Est. completion date: March 9, 2017
• Est. primary completion date: February 9, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male or female patients, age = 18 years

• A pulmonary specialist documented diagnosis of severe asthma according to the Global Initiative for Asthma and the German Asthma Network (GAN, www.german-asthma-net.de)

• Treatment with long-acting ß2-agonists (LABA) and inhaled corticosteroids (ICS) at a dose of at least 1000 µg beclomethasone (or equivalent) per day, - chronic oral corticosteroid (OCS) use is allowed Stable asthma medication for =1 month prior to screening (=4 months for omalizumab)

• Asthma Control Questionnaire (ACQ-5) score = 1.5

• Vitamin D insufficiency as defined by a serum vitamin D concentration of < 30 ng/ml but = 10 ng/ml at screening

Exclusion Criteria:

• Patients on vitamin D substitution

• Current smokers or ex-smokers with a smoking history of more than 10 pack-years

• Pregnant or nursing women or women who intend to become pregnant during the study

• Known impaired renal function (GFR < 30 ml/min) and history of physician-diagnosed nephrolithiasis

• Use of other investigational drugs during the study or within 30 days of screening

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• Vitamin D3
Initial single dose 100000 IU, beginning from the second day 4000 IU/day for 24 weeks.
• Placebo
Filling material: lactose monohydrate, cellulose, magnesium stearate

Locations

Country	Name	City	State
Germany	Pneumologische Gemeinschaftspraxis Dr. Rolke & Dr. Rückert	Aschaffenburg
Germany	Medizinische Klinik III für Pneumologie, allergologie, Schlaf- und Beatmungsmedizin, Berufsgenossenschaftliches Universitätsklinikum Bochum-Bergmannsheil GmbH	Bochum
Germany	IKF Pneumologie GmbH & Co.KG	Frankfurt
Germany	Pneumologisches Forschungsinstitut der LungenClinic Grosshansdorf	Grosshansdorf
Germany	Studienzentrum KPPK GmbH	Koblenz
Germany	KLB - Gesundheitsforschung Lübeck GmbH	Lübeck
Germany	Pneumologie, III. Medizinische Klinik, Universitätsmedizin der Johannes Gutenberg-Universität Mainz	Mainz
Germany	Universitätsklinikum Regensburg, Klinik und Poliklinik für Innere Medizin II/Pneumologie	Regensburg
Germany	Lungenpraxis Schleswig	Schleswig

Sponsors (2)

Lead Sponsor	Collaborator
Johannes Gutenberg University Mainz	German Federal Ministry of Education and Research

Country where clinical trial is conducted

Germany, 

References & Publications (3)

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. — View Citation

Korn S, Hübner M, Jung M, Blettner M, Buhl R. Severe and uncontrolled adult asthma is associated with vitamin D insufficiency and deficiency. Respir Res. 2013 Feb 22;14:25. doi: 10.1186/1465-9921-14-25. — View Citation

Martineau AR, MacLaughlin BD, Hooper RL, Barnes NC, Jolliffe DA, Greiller CL, Kilpin K, McLaughlin D, Fletcher G, Mein CA, Hoti M, Walton R, Grigg J, Timms PM, Rajakulasingam RK, Bhowmik A, Rowe M, Venton TR, Choudhury AB, Simcock DE, Sadique Z, Monteiro WR, Corrigan CJ, Hawrylowicz CM, Griffiths CJ. Double-blind randomised placebo-controlled trial of bolus-dose vitamin D3 supplementation in adults with asthma (ViDiAs). Thorax. 2015 May;70(5):451-7. doi: 10.1136/thoraxjnl-2014-206449. Epub 2015 Feb 27. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	relative dose reduction of ICS or OCS at week 24 as assessed by total ICS or OCS dose		24 weeks
Secondary	Exacerbations (rate of and time to first and subsequent exacerbations) as assessed by numbers of exacerbations		24 weeks and 30 weeks
Secondary	Asthma Control as assessed by ACQ score		at weeks 4, 8, 12, 14, 18, 20, 24, and 28
Secondary	Asthma Quality of Life as assessed by the Mini-AQLQ score		at weeks 12, 18, 24 and 28
Secondary	Pulmonary function test results as assessed by FEV1, FVC, IC, RV, TLC, and airway resistance		at weeks 4, 8, 12, 14, 18, 20, 24, and 28
Secondary	Levels of vitamin D as assessed by serum concentrations		at weeks 12, 18, 24 and 28
Secondary	Proportion of patients that achieved vitamin D sufficiency		at week 24
Secondary	Assessment of safety and tolerability as assessed by number of adverse events		up to 30 weeks
Secondary	Dyspnea as assessed by Baseline and Transition Dyspnea Indexes		at weeks 12, 18, 24 and 28