Vitamin D and Prebiotics for Intestinal Health in Cystic Fibrosis

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04118010

Enrollment

Registered

2019-10-07

Start date

2020-03-13

Completion date

2022-12-31

Last updated

2024-02-07

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Cystic Fibrosis, Dysbiosis

Keywords

Cystic Fibrosis, Gastrointestinal Dysbiosis, Vitamin D, Prebiotic, Inulin, Gut microbiome, Intestinal inflammation, Intestinal absorption

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.

Interventions

DRUGPlacebo vitamin D3

Matching to Vitamin D3 placebo capsules for 12 weeks

DRUGVitamin D3

High-dose vitamin D3 50,000 IU /week for 12 weeks

DRUGInulin

Chicory-derived prebiotic inulin 12 g/day for 12 weeks

DRUGPlacebo Inulin

Corn-derived maltodextrin 12g/day as the prebiotic placebo for 12 weeks

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

1. male and female patients (age \> 18 years) with confirmed CF by genetic mutation and/or sweat chloride testing, 2. not currently on oral or systemic antibiotics for pulmonary exacerbation, 3. vitamin D deficient/insufficient (25(OH)D, 6 - 30 ng/mL) with most recent 25(OH)D in the past 12 months, 4. use of CFTR modulator therapy is allowed

Exclusion criteria

1. severe vitamin D deficiency 25(OH)D ≤ 5 ng/mL or hypocalcemia or hypercalcemia, 2. active GI disease, abdominal pain and/or diarrhea, 3. chronic kidney disease worse than stage 3 (eGFR \< ml/min per 1.73 m2), 4. 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), 5. use of immunosuppressants or history of organ transplantation, 6. current use of probiotics or prebiotics

Design outcomes

Primary

Measure	Time frame	Description
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.
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.

Secondary

Measure	Time frame	Description
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 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 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.

Countries

United States

Participant flow

Participants by arm

Arm	Count
Vitamin D3 and Inulin Vitamin D3 50,000 IU/week and 12 g/day chicory-derived prebiotic inulin for 12 weeks Vitamin D3: High-dose vitamin D3 50,000 IU /week for 12 weeks Inulin: Chicory-derived prebiotic inulin 12 g/day for 12 weeks	7
Vitamin D3 and Placebo Inulin Vitamin D3 50,000 IU/week and 12 g/day corn-derived maltodextrin/day as the prebiotic placebo for 12 weeks Vitamin D3: High-dose vitamin D3 50,000 IU /week for 12 weeks Placebo Inulin: Corn-derived maltodextrin 12g/day as the prebiotic placebo for 12 weeks	8
Placebo Vitamin D3 and Inulin Matching to Vitamin D3 placebo capsules, and 12 g/day chicory-derived prebiotic inulin for 12 weeks Placebo vitamin D3: Matching to Vitamin D3 placebo capsules for 12 weeks Inulin: Chicory-derived prebiotic inulin 12 g/day for 12 weeks	7
Placebo Vitamin D3 and Placebo Inulin Matching to Vitamin D3 placebo capsules, and 12 g/day corn-derived maltodextrin/day as the prebiotic placebo for 12 weeks Placebo vitamin D3: Matching to Vitamin D3 placebo capsules for 12 weeks Placebo Inulin: Corn-derived maltodextrin 12g/day as the prebiotic placebo for 12 weeks	9
Total	31

Baseline characteristics

Characteristic	Vitamin D3 and Inulin	Total	Placebo Vitamin D3 and Placebo Inulin	Placebo Vitamin D3 and Inulin	Vitamin D3 and Placebo Inulin
Age, Continuous	29.3 years STANDARD_DEVIATION 5.4	33.1 years STANDARD_DEVIATION 11.9	34.4 years STANDARD_DEVIATION 14.2	39.6 years STANDARD_DEVIATION 15.6	29.3 years STANDARD_DEVIATION 7.9
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	2 Participants	2 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	7 Participants	29 Participants	7 Participants	7 Participants	8 Participants
Region of Enrollment United States	7 participants	31 participants	9 participants	7 participants	8 participants
Sex: Female, Male Female	1 Participants	13 Participants	4 Participants	5 Participants	3 Participants
Sex: Female, Male Male	6 Participants	18 Participants	5 Participants	2 Participants	5 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	0 / 7	0 / 8	0 / 7	0 / 9
other Total, other adverse events	0 / 7	0 / 8	0 / 7	0 / 9
serious Total, serious adverse events	0 / 7	0 / 8	0 / 7	0 / 9

Outcome results

Primary

Change in Species Richness Index From Baseline

Stool microbiota analysis will be measured using this ecological diversity measure. Stool samples will be collected using a stool kit provided to the participant.