Vitamin D in Bronchiolitis Obliterans Syndrome (VIT001)

• ClinicalTrials.gov Identifier: NCT01212406
• Recruitment Status: Completed
• First Posted: September 30, 2010
• Last Update Posted: November 11, 2015
• Sponsor: Universitaire Ziekenhuizen Leuven
• Collaborator: KU Leuven
• Information provided by (Responsible Party): Universitaire Ziekenhuizen Leuven

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Allograft Rejection; Lung Transplantation; Bronchiolitis Obliterans	Drug: Vitamin D	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: A Randomized Double Blind Placebo Controlled Trial With Vitamin D to Prevent Bronchiolitis Obliterans Syndrome After Lung Transplantation
• Study Start Date: October 2010
• Actual Primary Completion Date: September 2013
• Actual Study Completion Date: August 2015

Arms and Interventions

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 Name: 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 Name: D-Cure

Outcome Measures

Primary Outcome Measures :

1. Prevalence of Bronchiolitis Obliterans syndrome (BOS) (grade 1) at 2 years after transplantation [ Time Frame: 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. Prevalence of BOS (grade 1) at 3 years after transplantation [ Time Frame: 3 years after transplantation ]
   her-evaluation of data

Secondary Outcome Measures :

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

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:

• 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)

Contacts and Locations

Locations

Belgium

UZ Gasthuisberg

Leuven, Belgium, 3000

Sponsors and Collaborators

Universitaire Ziekenhuizen Leuven

KU Leuven

Investigators

• Principal Investigator: Geert M Verleden, MD, PhD; UZ gasthuisberg

More Information

Publications:

Ramirez AM, Wongtrakool C, Welch T, Steinmeyer A, Zügel 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, Götting 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.

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. Review.

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. Review.

• Responsible Party: Universitaire Ziekenhuizen Leuven
• ClinicalTrials.gov Identifier: NCT01212406
• Other Study ID Numbers: VIT001
• First Posted: September 30, 2010
• Last Update Posted: November 11, 2015
• Last Verified: October 2013

Keywords provided by Universitaire Ziekenhuizen Leuven:

Organ rejection; Lung transplantation; Bronchiolitis Obliterans; Vitamin D; Prevention

Additional relevant MeSH terms:

Bronchiolitis; Bronchiolitis Obliterans; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Infections; Vitamin D; Ergocalciferols; Vitamins; Micronutrients; Nutrients; Growth Substances; Physiological Effects of Drugs; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents