Vitamin D and Prebiotics for Intestinal Health in Cystic Fibrosis

Phase 4

Completed

Interventions: Drug: Placebo vitamin D3
Drug: Vitamin D3
Drug: Placebo Inulin
Drug: Inulin

Brief Summary: The study will assess if administration of high-dose vitamin D and a commonly used prebiotic (inulin) is effective to reduce gastrointestinal dysbiosis and to improve critical intestinal functions in Cystic Fibrosis with the additive or synergistic effects of the combination of vitamin D + inulin.

Detailed Description: Cystic fibrosis (CF) is the most common life-shortening genetic condition among Caucasians in the United States. Individuals with CF have an altered gastrointestinal (GI) microbiota, which may be a result of chronic systemic inflammation and infection, frequent use of antibiotics, and/or medically prescribed and habitual high-fat/high-calorie diets.

The study will assess if administration of high-dose vitamin D and a commonly used prebiotic (inulin) is effective to reduce gastrointestinal dysbiosis and to improve critical intestinal functions in Cystic Fibrosis.

Recruitment & Eligibility

Inclusion Criteria

male and female patients (age > 18 years) with confirmed CF by genetic mutation and/or sweat chloride testing,
not currently on oral or systemic antibiotics for pulmonary exacerbation,
vitamin D deficient/insufficient (25(OH)D, 6 - 30 ng/mL) with most recent 25(OH)D in the past 12 months,
use of CFTR modulator therapy is allowed

Exclusion Criteria

severe vitamin D deficiency 25(OH)D ≤ 5 ng/mL or hypocalcemia or hypercalcemia,
active GI disease, abdominal pain and/or diarrhea,
chronic kidney disease worse than stage 3 (eGFR < ml/min per 1.73 m2),
any vitamin D supplement use >2,000 IU or vitamin D analogue (patients who are taking more than 2,000 IU of vitamin D must agree to stop the vitamin D for 6 weeks and take less than 2,000 IU of vitamin D during the study),
use of immunosuppressants or history of organ transplantation,
current use of probiotics or prebiotics

Arm && Interventions

Group	Intervention	Description
Placebo vitamin D3 and placebo Inulin	Placebo vitamin D3	Matching to Vitamin D3 placebo capsules, and 12 g/day corn-derived maltodextrin/day as the prebiotic placebo for 12 weeks
Placebo vitamin D3 and placebo Inulin	Placebo Inulin	Matching to Vitamin D3 placebo capsules, and 12 g/day corn-derived maltodextrin/day as the prebiotic placebo for 12 weeks
Vitamin D3 and placebo Inulin	Placebo Inulin	Vitamin D3 50,000 IU/week and 12 g/day corn-derived maltodextrin/day as the prebiotic placebo for 12 weeks
Placebo vitamin D3 and Inulin	Placebo vitamin D3	Matching to Vitamin D3 placebo capsules, and 12 g/day chicory-derived prebiotic inulin for 12 weeks
Vitamin D3 and Inulin	Vitamin D3	Vitamin D3 50,000 IU/week and 12 g/day chicory-derived prebiotic inulin for 12 weeks
Vitamin D3 and placebo Inulin	Vitamin D3	Vitamin D3 50,000 IU/week and 12 g/day corn-derived maltodextrin/day as the prebiotic placebo for 12 weeks
Placebo vitamin D3 and Inulin	Inulin	Matching to Vitamin D3 placebo capsules, and 12 g/day chicory-derived prebiotic inulin for 12 weeks
Vitamin D3 and Inulin	Inulin	Vitamin D3 50,000 IU/week and 12 g/day chicory-derived prebiotic inulin for 12 weeks

Primary Outcome Measures

Name	Time	Method
Shannon Index	Baseline, 12 weeks post-intervention	The Shannon Index is a measure of diversity of microbial species that takes into account both abundance (the number of species present) and evenness (how close the numbers for each species are). The Shannon index can be calculated using the following equation: H= -∑(i=1)\^s pi ln(pi). A value of zero for H indicates that a community has only one species. The higher the value of H, the higher the diversity of species in a particular community. Sputum microbiota analysis was measured using this ecological diversity measure. Sputum samples were collected via a sputum kit.
Change in Species Richness Index From Baseline	Baseline, 12 weeks post-intervention	Stool microbiota analysis will be measured using this ecological diversity measure. Stool samples will be collected using a stool kit provided to the participant.

Secondary Outcome Measures

Name	Time	Method
Change in GI Microbiota Richness	Baseline, 12 weeks post-intervention	Changes in GI microbiota richness will be determined using 16S rRNA gene sequencing and microbiome-dependent metabolites pathways in stool and plasma using high-resolution metabolomics analysis.Changes in GI microbiota richness will be reported as a number of populations of microorganisms.
Change in GI Microbiota Diversity	Baseline, 12 weeks post-intervention	Changes in GI microbiota diversity will be determined using 16S rRNA gene sequencing and microbiome-dependent metabolites pathways in stool and plasma using high-resolution metabolomics analysis.Changes in GI microbiota diversity will be reported as the Shannon Index.
Change in GI Microbiota Composition	Baseline, 12 weeks post-intervention	Changes in GI microbiota composition will be determined using 16S rRNA gene sequencing and microbiome-dependent metabolites pathways in stool and plasma using high-resolution metabolomics analysis.Changes in GI microbiota composition will be reported as a percentage of bacteria.