Vitamin D in Bronchiolitis Obliterans Syndrome (VIT001)

A Randomized Double Blind Placebo Controlled Trial With Vitamin D to Prevent Bronchiolitis Obliterans Syndrome After Lung Transplantation

Vitamin D deficiency occurs in around 50% of our transplant population. Preventive treatment with Vitamin D (D-cure) can reduce the prevalence of Bronchiolitis Obliterans Syndrome after lung transplantation

Study Overview

• Status: Completed
• Conditions: Bronchiolitis Obliterans; Lung Transplantation; Allograft Rejection
• Intervention / Treatment: Drug: Vitamin D

Detailed Description

• Prospective, interventional, randomized, double-blind, placebo-controlled trial.
• Clinical setting (tertiary University Hospital).
• Investigator-driven, no pharmaceutical sponsor.
• Lung transplant recipients.
• Add-on of study-drug (placebo or vitamin D) to 'standard of care' (standardized, routine immunosuppressive and infectious prophylactic protocol).
• 1:1 inclusion ratio (placebo:Vitamin D).
• Randomisation at discharge after informed consent.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • Uz Gasthuisberg

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Stable LTx recipients at discharge after transplantation.
• Signed informed consent
• Adult (age at least 18 years old at moment of transplantation)
• Able to take oral medication

Exclusion Criteria:

• Prolonged and/or complicated Intensive care unit-course after transplantation.
• Early (<30 days post-transplant) post-operative death
• Major suture problems (airway stenosis or stent)
• Retransplantation (lung)
• Previous transplantation (solid organ)
• Multi-organ transplantation (lung+ other solid organ)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Olive oil	Drug: Vitamin D; Every month 100.000 units of vitamin D in syringe Exacta-Med Oral Dispenser during 2 years and re-evaluation after 3 years; Other Names: D-Cure
Experimental: Vitamin D; Addition of D-cure (100.000U) to standard care	Drug: Vitamin D; Every month 100.000 units of vitamin D in syringe Exacta-Med Oral Dispenser during 2 years and re-evaluation after 3 years; Other Names: D-Cure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of Bronchiolitis Obliterans syndrome (BOS) (grade 1) at 2 years after transplantation	BOS= decline in forced expiratory volume in 1 second (FEV1) with at least 80% compared to the best post-operative value	2 years after transplantation
Prevalence of BOS (grade 1) at 3 years after transplantation	her-evaluation of data	3 years after transplantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bronchoalveolar lavage	cellularity, protein and mRNA concentration and microbiology	during 2 and 3y of follow-up
Peripheral blood	Protein and mRNA concentration, cellularity	During 2 and 3 years of follow-up
Rejection rates	Acute rejection and lymphocytic bronchiolitis rates	During 2 and 3 years of follow-up
Reflux	clinical and biochemical approach	During 2 and 3 years of follow-up
Infection rates	cytomegalovirus (CMV) and non- CMV infection rates	During 2 and 3 years of follow-up

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven
• Collaborators: KU Leuven
• Investigators: Principal Investigator: Geert M Verleden, MD, PhD, Uz Gasthuisberg

Publications and helpful links

General Publications

• Estenne M, Maurer JR, Boehler A, Egan JJ, Frost A, Hertz M, Mallory GB, Snell GI, Yousem S. Bronchiolitis obliterans syndrome 2001: an update of the diagnostic criteria. J Heart Lung Transplant. 2002 Mar;21(3):297-310. doi: 10.1016/s1053-2498(02)00398-4. No abstract available.
• Vanaudenaerde BM, Meyts I, Vos R, Geudens N, De Wever W, Verbeken EK, Van Raemdonck DE, Dupont LJ, Verleden GM. A dichotomy in bronchiolitis obliterans syndrome after lung transplantation revealed by azithromycin therapy. Eur Respir J. 2008 Oct;32(4):832-43. doi: 10.1183/09031936.00134307.
• Ramirez AM, Wongtrakool C, Welch T, Steinmeyer A, Zugel U, Roman J. Vitamin D inhibition of pro-fibrotic effects of transforming growth factor beta1 in lung fibroblasts and epithelial cells. J Steroid Biochem Mol Biol. 2010 Feb 15;118(3):142-50. doi: 10.1016/j.jsbmb.2009.11.004. Epub 2009 Nov 17.
• Zittermann A, Schleithoff SS, Gotting C, Fuchs U, Kuhn J, Kleesiek K, Tenderich G, Koerfer R. Calcitriol deficiency and 1-year mortality in cardiac transplant recipients. Transplantation. 2009 Jan 15;87(1):118-24. doi: 10.1097/TP.0b013e31818c2708.
• Janssens W, Bouillon R, Claes B, Carremans C, Lehouck A, Buysschaert I, Coolen J, Mathieu C, Decramer M, Lambrechts D. Vitamin D deficiency is highly prevalent in COPD and correlates with variants in the vitamin D-binding gene. Thorax. 2010 Mar;65(3):215-20. doi: 10.1136/thx.2009.120659. Epub 2009 Dec 8.

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): September 1, 2013
• Study Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: September 28, 2010
• First Submitted That Met QC Criteria: September 29, 2010
• First Posted (Estimate): September 30, 2010

Study Record Updates

• Last Update Posted (Estimate): November 11, 2015
• Last Update Submitted That Met QC Criteria: November 10, 2015
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Keywords: Vitamin D; Prevention; Lung transplantation; Organ rejection; Bronchiolitis Obliterans
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Bronchitis; Bronchiolitis; Bronchiolitis Obliterans; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Vitamin D
• Other Study ID Numbers: VIT001