Vitamin D and Prebiotics for Intestinal Health in Cystic Fibrosis

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.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis; Dysbiosis
• Intervention / Treatment: Drug: Vitamin D3; Drug: Inulin; Drug: Placebo Inulin; Drug: Placebo vitamin D3

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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Vin Tangpricha, MD; Phone Number: 404-727-7254; Email: vtangpr@emory.edu

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Vitamin D3 and Inulin; Vitamin D3 50,000 IU/week and 12 g/day chicory-derived prebiotic inulin for 12 weeks	Drug: Vitamin D3; High-dose vitamin D3 50,000 IU /week for 12 weeks; Drug: Inulin; Chicory-derived prebiotic inulin 12 g/day for 12 weeks
Active Comparator: 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	Drug: Vitamin D3; High-dose vitamin D3 50,000 IU /week for 12 weeks; Drug: Placebo Inulin; Corn-derived maltodextrin 12g/day as the prebiotic placebo for 12 weeks
Active Comparator: Placebo vitamin D3 and Inulin; Matching to Vitamin D3 placebo capsules, and 12 g/day chicory-derived prebiotic inulin for 12 weeks	Drug: Inulin; Chicory-derived prebiotic inulin 12 g/day for 12 weeks; Drug: Placebo vitamin D3; Matching to Vitamin D3 placebo capsules for 12 weeks
Placebo Comparator: 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	Drug: Placebo Inulin; Corn-derived maltodextrin 12g/day as the prebiotic placebo for 12 weeks; Drug: Placebo vitamin D3; Matching to Vitamin D3 placebo capsules for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Shannon Index	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.	Baseline, 12 weeks post-intervention
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.	Baseline, 12 weeks post-intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in GI Microbiota Diversity	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.	Baseline, 12 weeks post-intervention
Change in GI Microbiota Richness	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.	Baseline, 12 weeks post-intervention
Change in GI Microbiota Composition	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.	Baseline, 12 weeks post-intervention

Collaborators and Investigators

• Sponsor: Emory University
• Investigators: Principal Investigator: Vin Tangpricha, MD, Emory University

Study record dates

Study Major Dates

• Study Start (Actual): March 13, 2020
• Primary Completion (Actual): December 31, 2022
• Study Completion (Actual): December 31, 2022

Study Registration Dates

• First Submitted: October 4, 2019
• First Submitted That Met QC Criteria: October 4, 2019
• First Posted (Actual): October 7, 2019

Study Record Updates

• Last Update Posted (Actual): February 7, 2024
• Last Update Submitted That Met QC Criteria: January 13, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Vitamin D; Prebiotic; Cystic Fibrosis; Intestinal inflammation; Intestinal absorption; Gut microbiome; Inulin; Gastrointestinal Dysbiosis
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis; Dysbiosis; Physiological Effects of Drugs; Micronutrients; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol; Vitamins; Ergocalciferols
• Other Study ID Numbers: IRB00114230

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual de-identified participant data (including data dictionaries) be shared with listed investigators
• IPD Sharing Time Frame: Projected December 2023
• IPD Sharing Access Criteria: Protocol and reported primary and secondary outcomes will be be shared on request for statistical analyses with listed investigators
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No