Prospective Intervention Study on Vitamin D in Patients With Cystic Fibrosis

Study Overview
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Brief Summary
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The vast majority of Cystic Fibrosis (CF) patients worldwide are vitamin D insufficient. There is no evidence of benefit of vitamin D supplementation for CF patients yet. However, descriptive cross-sectional studies suggest that vitamin D might be beneficial with respect to bone health, as well as to the newly described non-classical functions of vitamin D such as the potential anti-diabetic and immunomodulatory effects. To prove causation, and to determine which serum vitamin D concentration is optimal for CF patients, vitamin D supplementation interventional studies are needed, such as our trial.

Official Title
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5-month Pilot Intervention Study on Vitamin D in Patients With Cystic Fibrosis

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Dietary Supplement: Supplementation with vitamin D2/D3


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Established diagnosis of cystic fibrosis Age 6 years and more Serum 25-hydroxy vitamin D concentration at the latest visit < 75 nmol/L Exclusion Criteria: Pregnancy or lactation Established diagnosis of CF-related diabetes CF-related liver disease Status post transplantation (lung, liver or other) Long-term corticosteroid treatment per os Hypercalcaemia or kidney stones Use of tanning beds more often than once a month At inclusion, plans to travel to a sunny location for more than 1 week during the study period Any known disorders of the endocrine system affecting vitamin D metabolism (hyperparathyroidism, malignancy, advanced renal disease) Inclusion into another study testing immunomodulatory substances

Ages Eligible for Study
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Minimum Age: 6 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ergocalciferol<br>Patients younger than 16 years of age are administered 35,000 IU ergocalciferol per week divided into doses 5000 IU per day as a starting dose that is further adjusted by serum 25-hydroxy vitamin D concentration monitoring. Patients 16 or more years of age are administered 50,000 IU ergocalciferol per week divided into doses 7150 IU per day as a starting dose that is further adjusted by serum 25-hydroxy vitamin D concentration monitoring. | Dietary Supplement: Supplementation with vitamin D2/D3<br>* Patients younger than 16 years of age are administered 35,000 IU ergo-/chole-calciferol per week divided into doses 5000 IU per day as a starting dose that is further adjusted by serum 25-hydroxy vitamin D concentration monitoring. The intervention time is 3 months, followed by 2-months wash-out period when patients do not take any more extra vitamin D but they are still monitored. Patients 16 or more years of age are administered 50,000 IU ergo-/chole-calciferol per week divided into doses 7150 IU per day as a starting dose that is further adjusted by serum 25-hydroxy vitamin D concentration monitoring.<br>|
| Experimental: Cholecalciferol<br>Patients younger than 16 years of age are administered 35,000 IU cholecalciferol per week divided into doses 5000 IU per day as a starting dose that is further adjusted by serum 25-hydroxy vitamin D concentration monitoring. Patients 16 or more years of age are administered 50,000 IU cholecalciferol per week divided into doses 7150 IU per day as a starting dose that is further adjusted by serum 25-hydroxy vitamin D concentration monitoring. | Dietary Supplement: Supplementation with vitamin D2/D3<br>* Patients younger than 16 years of age are administered 35,000 IU ergo-/chole-calciferol per week divided into doses 5000 IU per day as a starting dose that is further adjusted by serum 25-hydroxy vitamin D concentration monitoring. The intervention time is 3 months, followed by 2-months wash-out period when patients do not take any more extra vitamin D but they are still monitored. Patients 16 or more years of age are administered 50,000 IU ergo-/chole-calciferol per week divided into doses 7150 IU per day as a starting dose that is further adjusted by serum 25-hydroxy vitamin D concentration monitoring.<br>|
| No Intervention: Control<br>Patients continue their ordinary vitamin supplementation without getting extra vitamin D supplements. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum 25-hydroxy vitamin D | This pilot study is primarily designed for establishing effective vitamin D dosing in our specific patient population, and only secondarily designed (and thus, not powered for) for the secondary outcome measures. The results of this study will make it possible for the first time to power the follow-up long-term study for some of the secondary outcome measures followed in this pilot study, some of which might therefore become primary outcome measures in the follow-up study. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Parathyroid hormone (PTH) | As a surrogate marker of bone health | 3 months | 
| Inflammatory parameters | Cytokine profiles, antimicrobial peptides, peripheral blood mononuclear cell profiles, immunoglobulines, acute phase markers, sedimentation rate and other | 3 months | 
| Infection parameters | Number of days on intravenous antibiotic treatment; number of infectious episodes; number of common cold episodes; relative number of sputum samples positive for pathological bacteria; and other | 3 months | 
| Lung function parameters | FEV1, FVC, PEF, FEF25, FEF50, FEF75 and other | 3 months | 
| Glucose tolerance parameters | Insulin, C-peptide, glucagon, fasting plasma glucose, HbA1c, 3-hour 75-g oral glucose tolerance test | 3 months | 
| Adherence with vitamin D treatment | Semi-quantitative assessment by a questionnaire (thus, a patient-reported outcome) | 3 months | 
| Disease-specific quality of life | Assessment using CFQ-R questionnaire, specifically designed to measure the quality of life in CF patients | 3 months | 
| Plasma calcium | Proportion of patients with albumin-corrected serum calcium increasing to a concentration greater than 2,75 mmol/L in patients with no hypercalcaemia before vitamin D supplementation was started. | 3 months | 
| Relative number of patients reaching high abnormal 25(OH)D concentrations | Proportion of patients in the intervention arms reaching 25(OH)D >250 nmol/L | 3 months | 
| Proportion of patients reaching toxic 25(OH)D concentrations | Proportion of patients in the intervention arms reaching 25(OH)D >375 nmol/L | 3 months | 
| Proportion of patients with suspect hypercalcaemia symptoms | Proportion of patients with suspect hypercalcaemia symptoms in the intervention arms | 3 months |