Effect of Vitamin D as add-on Therapy for Vitamin D Insufficient Patients With Severe Asthma (EVITA)
Primary Purpose
Asthma
Status
Terminated
Phase
Phase 4
Locations
Germany
Study Type
Interventional
Intervention
Vitamin D3
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Asthma focused on measuring severe asthma, vitamin D, treatment
Eligibility Criteria
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 β2-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
Sites / Locations
- Pneumologische Gemeinschaftspraxis Dr. Rolke & Dr. Rückert
- Medizinische Klinik III für Pneumologie, allergologie, Schlaf- und Beatmungsmedizin, Berufsgenossenschaftliches Universitätsklinikum Bochum-Bergmannsheil GmbH
- IKF Pneumologie GmbH & Co.KG
- Pneumologisches Forschungsinstitut der LungenClinic Grosshansdorf
- Studienzentrum KPPK GmbH
- KLB - Gesundheitsforschung Lübeck GmbH
- Pneumologie, III. Medizinische Klinik, Universitätsmedizin der Johannes Gutenberg-Universität Mainz
- Universitätsklinikum Regensburg, Klinik und Poliklinik für Innere Medizin II/Pneumologie
- Lungenpraxis Schleswig
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Vitamin D3
Placebo
Arm Description
Initial single dose 100000 IU, beginning from the second day 4000 IU/day for 24 weeks
Amount of Placebo capsules corresponding to initial single dose of Vitamin D3, beginning from the second day amount of capsules corresponding to daily dose of Vitamin D for 24 weeks
Outcomes
Primary Outcome Measures
relative dose reduction of ICS or OCS at week 24 as assessed by total ICS or OCS dose
Secondary Outcome Measures
Exacerbations (rate of and time to first and subsequent exacerbations) as assessed by numbers of exacerbations
Asthma Control as assessed by ACQ score
Asthma Quality of Life as assessed by the Mini-AQLQ score
Pulmonary function test results as assessed by FEV1, FVC, IC, RV, TLC, and airway resistance
Levels of vitamin D as assessed by serum concentrations
Proportion of patients that achieved vitamin D sufficiency
Assessment of safety and tolerability as assessed by number of adverse events
Dyspnea as assessed by Baseline and Transition Dyspnea Indexes
Full Information
NCT ID
NCT02424552
First Posted
April 14, 2015
Last Updated
April 28, 2017
Sponsor
Johannes Gutenberg University Mainz
Collaborators
German Federal Ministry of Education and Research
1. Study Identification
Unique Protocol Identification Number
NCT02424552
Brief Title
Effect of Vitamin D as add-on Therapy for Vitamin D Insufficient Patients With Severe Asthma
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2017
Overall Recruitment Status
Terminated
Why Stopped
recruitment problems
Study Start Date
June 26, 2015 (Actual)
Primary Completion Date
February 9, 2017 (Actual)
Study Completion Date
March 9, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Johannes Gutenberg University Mainz
Collaborators
German Federal Ministry of Education and Research
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief 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.
Detailed 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Asthma
Keywords
severe asthma, vitamin D, treatment
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
54 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Vitamin D3
Arm Type
Experimental
Arm Description
Initial single dose 100000 IU, beginning from the second day 4000 IU/day for 24 weeks
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Amount of Placebo capsules corresponding to initial single dose of Vitamin D3, beginning from the second day amount of capsules corresponding to daily dose of Vitamin D for 24 weeks
Intervention Type
Drug
Intervention Name(s)
Vitamin D3
Other Intervention Name(s)
Cholecalciferol
Intervention Description
Initial single dose 100000 IU, beginning from the second day 4000 IU/day for 24 weeks.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Filling material: lactose monohydrate, cellulose, magnesium stearate
Primary Outcome Measure Information:
Title
relative dose reduction of ICS or OCS at week 24 as assessed by total ICS or OCS dose
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Exacerbations (rate of and time to first and subsequent exacerbations) as assessed by numbers of exacerbations
Time Frame
24 weeks and 30 weeks
Title
Asthma Control as assessed by ACQ score
Time Frame
at weeks 4, 8, 12, 14, 18, 20, 24, and 28
Title
Asthma Quality of Life as assessed by the Mini-AQLQ score
Time Frame
at weeks 12, 18, 24 and 28
Title
Pulmonary function test results as assessed by FEV1, FVC, IC, RV, TLC, and airway resistance
Time Frame
at weeks 4, 8, 12, 14, 18, 20, 24, and 28
Title
Levels of vitamin D as assessed by serum concentrations
Time Frame
at weeks 12, 18, 24 and 28
Title
Proportion of patients that achieved vitamin D sufficiency
Time Frame
at week 24
Title
Assessment of safety and tolerability as assessed by number of adverse events
Time Frame
up to 30 weeks
Title
Dyspnea as assessed by Baseline and Transition Dyspnea Indexes
Time Frame
at weeks 12, 18, 24 and 28
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 β2-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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stephanie Korn, MD
Organizational Affiliation
Johannes Gutenberg University Mainz
Official's Role
Principal Investigator
Facility Information:
Facility Name
Pneumologische Gemeinschaftspraxis Dr. Rolke & Dr. Rückert
City
Aschaffenburg
ZIP/Postal Code
D-63739
Country
Germany
Facility Name
Medizinische Klinik III für Pneumologie, allergologie, Schlaf- und Beatmungsmedizin, Berufsgenossenschaftliches Universitätsklinikum Bochum-Bergmannsheil GmbH
City
Bochum
ZIP/Postal Code
D-44789
Country
Germany
Facility Name
IKF Pneumologie GmbH & Co.KG
City
Frankfurt
ZIP/Postal Code
D-60596
Country
Germany
Facility Name
Pneumologisches Forschungsinstitut der LungenClinic Grosshansdorf
City
Grosshansdorf
ZIP/Postal Code
D-22927
Country
Germany
Facility Name
Studienzentrum KPPK GmbH
City
Koblenz
ZIP/Postal Code
D-56068
Country
Germany
Facility Name
KLB - Gesundheitsforschung Lübeck GmbH
City
Lübeck
ZIP/Postal Code
D-23552
Country
Germany
Facility Name
Pneumologie, III. Medizinische Klinik, Universitätsmedizin der Johannes Gutenberg-Universität Mainz
City
Mainz
ZIP/Postal Code
D-55131
Country
Germany
Facility Name
Universitätsklinikum Regensburg, Klinik und Poliklinik für Innere Medizin II/Pneumologie
City
Regensburg
ZIP/Postal Code
D-93053
Country
Germany
Facility Name
Lungenpraxis Schleswig
City
Schleswig
ZIP/Postal Code
D-24837
Country
Germany
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
23432854
Citation
Korn S, Hubner 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(1):25. doi: 10.1186/1465-9921-14-25.
Results Reference
background
PubMed Identifier
25724847
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.
Results Reference
background
PubMed Identifier
24838406
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.
Results Reference
background
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Effect of Vitamin D as add-on Therapy for Vitamin D Insufficient Patients With Severe Asthma
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