Vitamin D and Microbiota in Cystic Fibrosis

Study Overview
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Brief Summary
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The objective of this study is to assess the effects of a high-dose vitamin D3 on the composition of gut and lung microbiota in adolescents and adults with cystic fibrosis who are vitamin D deficient.

Detailed Description
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Monocentric, double-blind, randomized, placebo-controlled, interventional pilot study to investigate the beneficial effects of high dose vitamin D supplementation on gut and lung microbiota in patients with cystic fibrosis who are vitamin D insufficient.

Official Title
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Pilot Study Evaluating the Role of Vitamin D Repletion on Gut and Lung Microbiota in Cystic Fibrosis

Conditions
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Vitamin D Deficiency, Cystic Fibrosis

Intervention / Treatment
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* Dietary Supplement: High-Dose Vitamin D3
* Other: Stool Sample
* Other: Sputum Sample
* Other: Sham Comparator
* Procedure: Blood draw


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Presenting to the Cystic fibrosis clinic for routine follow up of cystic fibrosis Serum 25(OH)D concentrations obtained within 2 months of enrollment Able to tolerate oral medications Exclusion Criteria: Inability to obtain or declined informed consent from the subject and/or legally authorized representative Pregnancy or plans to become pregnant in the next 3 months History of disorders associated with hypercalcemia including parathyroid disease Current hypercalcemia (albumin-corrected serum calcium >10.8 mg/dL or ionized calcium >5.2 mg/dL) History of nephrolithiasis with active symptoms within the past two years Chronic kidney disease worse than stage III (<60 ml/min) Current significant hepatic dysfunction total bilirubin > 2.5 mg/dL with direct bilirubin > 1.0 mg/dL Current use of cytotoxic or immunosuppressive drugs History of AIDS History of illicit drug abuse (defined as history of enrollment into a drug rehabilitation program or hospital visits due to drug use within the past 3 years or any use of the following drugs in the past 6 months (cocaine, opiates, amphetamines, marijuana) or any positive toxicology screen for (cocaine, opiates, amphetamines, marijuana) Too ill to participate in study based on investigator's or study team's opinion Current enrollment in another intervention trial In addition we amended our study with three additional criteria 11) systemic antibiotic use in the last 4 weeks, 12) use of probiotics and, 13) inflammatory bowel disease, four months after the start of the study and after 12 subjects were randomized, as we considered that these factors may also influence our study endpoints. Of the 12 subjects who were randomized, only 4 would have been excluded.

Ages Eligible for Study
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Minimum Age: 18 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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Participants with vitamin D deficiency - treatment group<br>Participants with 25-hydroxyvitamin D (25(OH)D) ≤30 ng/mL taking oral high-dose vitamin D3 (50,000 IU) once a week and providing stool and sputum sample at screening and 3 months after screening. | Dietary Supplement: High-Dose Vitamin D3<br>* 50,000 IU of oral vitamin D3 once a week (the standard of care for repletion of vitamin D status by the Cystic fibrosis Foundation)<br>* Other names: Cholecalciferol;Other: Stool Sample<br>* Participants will be asked to provide a stool sample in a collection container for analysis of stool microbiota. This will be done upon enrollment (baseline) and at 3 month follow-up.<br>Other: Sputum Sample<br>* Participants will be asked to collect their sputum (the thick mucus or phlegm that is expelled from the lower respiratory tract through coughing) into a kit. This will be done upon enrollment (baseline) and at 3 month follow-up.<br>Procedure: Blood draw<br>* Participants will be asked to provide 30 ml of blood collected via a blood draw to measure 25 (OH)D serum concentration and other nutrient markers related to vitamin D including Parathyroid hormone, fibroblast growth factor-23, vitamin D binding protein and markers of immune system/inflammation. This will be done at baseline and at 3 months follow up.<br>|
| Sham Comparator: Participants with vitamin D deficiency - placebo group<br>Participants with 25-hydroxyvitamin D (25(OH)D) concentrations ≤30 ng/mL taking a sham comparator (placebo) once a week and providing stool sample and sputum sample at screening and 3 months after screening. | Other: Stool Sample<br>* Participants will be asked to provide a stool sample in a collection container for analysis of stool microbiota. This will be done upon enrollment (baseline) and at 3 month follow-up.<br>Other: Sputum Sample<br>* Participants will be asked to collect their sputum (the thick mucus or phlegm that is expelled from the lower respiratory tract through coughing) into a kit. This will be done upon enrollment (baseline) and at 3 month follow-up.<br>Other: Sham Comparator<br>* A placebo capsule taken once a week (manufactured by the same company that makes the Vitamin D supplement).<br>* Other names: Placebo;Procedure: Blood draw<br>* Participants will be asked to provide 30 ml of blood collected via a blood draw to measure 25 (OH)D serum concentration and other nutrient markers related to vitamin D including Parathyroid hormone, fibroblast growth factor-23, vitamin D binding protein and markers of immune system/inflammation. This will be done at baseline and at 3 months follow up.<br>|
| Other: Participants without vitamin D deficiency<br>Participants with 25-hydroxyvitamin D (25(OH)D) concentrations > 30 ng/mL with no intervention and providing stool sample and sputum sample at screening and 3 months after screening. | Other: Stool Sample<br>* Participants will be asked to provide a stool sample in a collection container for analysis of stool microbiota. This will be done upon enrollment (baseline) and at 3 month follow-up.<br>Other: Sputum Sample<br>* Participants will be asked to collect their sputum (the thick mucus or phlegm that is expelled from the lower respiratory tract through coughing) into a kit. This will be done upon enrollment (baseline) and at 3 month follow-up.<br>Procedure: Blood draw<br>* Participants will be asked to provide 30 ml of blood collected via a blood draw to measure 25 (OH)D serum concentration and other nutrient markers related to vitamin D including Parathyroid hormone, fibroblast growth factor-23, vitamin D binding protein and markers of immune system/inflammation. This will be done at baseline and at 3 months follow up.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Shannon Index | Sputum microbiota analysis will be measured using this ecological diversity measure. Sputum samples will be collected via a sputum kit. | Change from baseline shannon Index at 3 months after initiation of treatment | 
| Species Richness Index | Stool microbiota analysis will be measured using this ecological diversity measure. Stool samples will be collected using a stool kit provided to the participant. | Change from baseline Species Richness Index at 3 months after initiation of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum 25(OH)D levels (and other nutritional markers related to vitamin D including nutrient levels, parathyroid hormone, fibroblast growth factor-23, free 25(OH)D, vitamin D binding protein | Collected via blood draw. | At baseline and 3 months after initiation of treatment | 
| Forced expiratory volume in 1 second (FEV1) | Spirometry (is a common office test used to assess how well the participant's lungs work by measuring how much air the participant inhales, how much the participant exhales and how quickly the participant exhales) to assess the impact of vitamin D status on lung function. Spirometry results will only be collected if they are done as part of the participants routine care. | Change in Forced expiratory volume in 1 second( FEV1) at 3 months after initiation of treatment | 
| Measures of plasma oxidative stress by assessing plasma aminothiol concentrations (glutathione, glutathione disulfide, cysteine, cystine) and their redox potentials. | Collected via blood draw. | At baseline and 3 months after initiation of treatment | 
| Measures of inflammation by assessing plasma IL-6, TNF-alpha, MCP-1, and IL-8 concentrations | Collected via blood draw. | At baseline and 3 months after initiation of treatment | 
| Forced vital capacity (FVC) | Spirometry (is a common office test used to assess how well the participant's lungs work by measuring how much air the participant inhales, how much the participant exhales and how quickly the participant exhales) to assess the impact of vitamin D status on lung function. Spirometry results will only be collected if they are done as part of the participants routine care. | Change in Forced vital capacity( FVC) at 3 months after initiation of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Clinical Endocrinology, Immunology, Inflammation, Microbiology, Respiratory Disorders, Vitamins