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Vitamin D and Prebiotics for Intestinal Health in Cystic Fibrosis

Primary Purpose

Cystic Fibrosis, Dysbiosis

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Vitamin D3
Placebo vitamin D3
Inulin
Placebo Inulin
Sponsored by
Emory University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cystic Fibrosis focused on measuring Cystic Fibrosis, Gastrointestinal Dysbiosis, Vitamin D, Prebiotic, Inulin, Gut microbiome, Intestinal inflammation, Intestinal absorption

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Emory Clinic

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Active Comparator

Active Comparator

Placebo Comparator

Arm Label

Vitamin D3 and Inulin

Vitamin D3 and placebo Inulin

Placebo vitamin D3 and Inulin

Placebo vitamin D3 and placebo Inulin

Arm Description

Vitamin D3 50,000 IU/week and 12 g/day chicory-derived prebiotic inulin for 12 weeks

Vitamin D3 50,000 IU/week and 12 g/day corn-derived maltodextrin/day as the prebiotic placebo for 12 weeks

Matching to Vitamin D3 placebo capsules, and 12 g/day chicory-derived prebiotic inulin for 12 weeks

Matching to Vitamin D3 placebo capsules, and 12 g/day corn-derived maltodextrin/day as the prebiotic placebo for 12 weeks

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
Change in calprotectin level in the stool
Calprotectin is a protein released by a type of white blood cell called a neutrophil. When there is inflammation in the gastrointestinal (GI) tract, neutrophils move to the area and release calprotectin, resulting in an increased level in the stool.
Change in lipocalin-2 blood level
Lipocalin-2 (LCN2), also known as oncogene 24p3 or neutrophil gelatinase-associated lipocalin (NGAL), is a protein that in humans is encoded by the LCN2 gene.NGAL is involved in innate immunity by sequestrating iron that in turn limits bacterial growth.It is expressed in neutrophils and in low levels in the kidney, prostate, and epithelia of the respiratory and alimentary tracts.NGAL is used as a biomarker of kidney injury.
Change in serum C-reactive protein blood level
C-reactive protein (CRP) is a substance produced by the liver in response to inflammation. A high level of CRP in the blood is a marker of inflammation.
Change in tumor necrosis factor (TNF) blood level
Tumor necrosis factor (TNF) is a multifunctional cytokine that plays important roles in diverse cellular events such as cell survival, proliferation, differentiation, and death. As a pro-inflammatory cytokine, TNF is secreted by inflammatory cells, which may be involved in inflammation-associated carcinogenesis.
Change in interleukin-6 blood level
Interleukin 6 (IL-6) is an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine.
Change in interleukin-8 blood level
IL-8 is a chemotactic factor that attracts neutrophils, basophils, and T-cells, but not monocytes. It is also involved in neutrophil activation. It is released from several cell types in response to an inflammatory stimulus.

Full Information

First Posted
October 4, 2019
Last Updated
March 16, 2023
Sponsor
Emory University
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1. Study Identification

Unique Protocol Identification Number
NCT04118010
Brief Title
Vitamin D and Prebiotics for Intestinal Health in Cystic Fibrosis
Official Title
Vitamin D and Prebiotics for Intestinal Health in Cystic Fibrosis
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Completed
Study Start Date
March 13, 2020 (Actual)
Primary Completion Date
December 31, 2022 (Actual)
Study Completion Date
December 31, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Emory University

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystic Fibrosis, Dysbiosis
Keywords
Cystic Fibrosis, Gastrointestinal Dysbiosis, Vitamin D, Prebiotic, Inulin, Gut microbiome, Intestinal inflammation, Intestinal absorption

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
40 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Vitamin D3 and Inulin
Arm Type
Active Comparator
Arm Description
Vitamin D3 50,000 IU/week and 12 g/day chicory-derived prebiotic inulin for 12 weeks
Arm Title
Vitamin D3 and placebo Inulin
Arm Type
Active Comparator
Arm Description
Vitamin D3 50,000 IU/week and 12 g/day corn-derived maltodextrin/day as the prebiotic placebo for 12 weeks
Arm Title
Placebo vitamin D3 and Inulin
Arm Type
Active Comparator
Arm Description
Matching to Vitamin D3 placebo capsules, and 12 g/day chicory-derived prebiotic inulin for 12 weeks
Arm Title
Placebo vitamin D3 and placebo Inulin
Arm Type
Placebo Comparator
Arm Description
Matching to Vitamin D3 placebo capsules, and 12 g/day corn-derived maltodextrin/day as the prebiotic placebo for 12 weeks
Intervention Type
Drug
Intervention Name(s)
Vitamin D3
Intervention Description
High-dose vitamin D3 50,000 IU /week for 12 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo vitamin D3
Intervention Description
Matching to Vitamin D3 placebo capsules for 12 weeks
Intervention Type
Drug
Intervention Name(s)
Inulin
Intervention Description
Chicory-derived prebiotic inulin 12 g/day for 12 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo Inulin
Intervention Description
Corn-derived maltodextrin 12g/day as the prebiotic placebo for 12 weeks
Primary Outcome Measure Information:
Title
Change in GI microbiota composition
Description
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.
Time Frame
Baseline, 12 weeks
Secondary Outcome Measure Information:
Title
Change in GI microbiota diversity
Description
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.
Time Frame
Baseline, 12 weeks
Title
Change in GI microbiota richness
Description
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.
Time Frame
Baseline, 12 weeks
Title
Change in calprotectin level in the stool
Description
Calprotectin is a protein released by a type of white blood cell called a neutrophil. When there is inflammation in the gastrointestinal (GI) tract, neutrophils move to the area and release calprotectin, resulting in an increased level in the stool.
Time Frame
Baseline, 12 weeks
Title
Change in lipocalin-2 blood level
Description
Lipocalin-2 (LCN2), also known as oncogene 24p3 or neutrophil gelatinase-associated lipocalin (NGAL), is a protein that in humans is encoded by the LCN2 gene.NGAL is involved in innate immunity by sequestrating iron that in turn limits bacterial growth.It is expressed in neutrophils and in low levels in the kidney, prostate, and epithelia of the respiratory and alimentary tracts.NGAL is used as a biomarker of kidney injury.
Time Frame
Baseline, 12 weeks
Title
Change in serum C-reactive protein blood level
Description
C-reactive protein (CRP) is a substance produced by the liver in response to inflammation. A high level of CRP in the blood is a marker of inflammation.
Time Frame
Baseline, 12 weeks
Title
Change in tumor necrosis factor (TNF) blood level
Description
Tumor necrosis factor (TNF) is a multifunctional cytokine that plays important roles in diverse cellular events such as cell survival, proliferation, differentiation, and death. As a pro-inflammatory cytokine, TNF is secreted by inflammatory cells, which may be involved in inflammation-associated carcinogenesis.
Time Frame
Baseline, 12 weeks
Title
Change in interleukin-6 blood level
Description
Interleukin 6 (IL-6) is an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine.
Time Frame
Baseline, 12 weeks
Title
Change in interleukin-8 blood level
Description
IL-8 is a chemotactic factor that attracts neutrophils, basophils, and T-cells, but not monocytes. It is also involved in neutrophil activation. It is released from several cell types in response to an inflammatory stimulus.
Time Frame
Baseline, 12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Vin Tangpricha, MD
Organizational Affiliation
Emory University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Emory Clinic
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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

Learn more about this trial

Vitamin D and Prebiotics for Intestinal Health in Cystic Fibrosis

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