Vitamin D and Microbiota in Cystic Fibrosis

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

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.

Study Overview

• Status: Completed
• Conditions: Vitamin D Deficiency; Cystic Fibrosis
• Intervention / Treatment: Dietary supplement: High-Dose Vitamin D3; Other: Stool Sample; Other: Sputum Sample; Procedure: Blood draw; Other: Sham Comparator

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Not Applicable

Contacts and Locations

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
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Participants with vitamin D deficiency - treatment group; 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; 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); Other Names: Cholecalciferol; Other: Stool Sample; 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.; Other: Sputum Sample; 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.; Procedure: Blood draw; 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.
Sham Comparator: Participants with vitamin D deficiency - placebo group; 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; 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.; Other: Sputum Sample; 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.; Procedure: Blood draw; 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.; Other: Sham Comparator; A placebo capsule taken once a week (manufactured by the same company that makes the Vitamin D supplement).; Other Names: Placebo
Other: Participants without vitamin D deficiency; 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; 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.; Other: Sputum Sample; 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.; Procedure: Blood draw; 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.

What is the study measuring?

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

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Kanhere M, He J, Chassaing B, Ziegler TR, Alvarez JA, Ivie EA, Hao L, Hanfelt J, Gewirtz AT, Tangpricha V. Bolus Weekly Vitamin D3 Supplementation Impacts Gut and Airway Microbiota in Adults With Cystic Fibrosis: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial. J Clin Endocrinol Metab. 2018 Feb 1;103(2):564-574. doi: 10.1210/jc.2017-01983.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2015
• Primary Completion (Actual): February 1, 2017
• Study Completion (Actual): April 1, 2017

Study Registration Dates

• First Submitted: October 20, 2015
• First Submitted That Met QC Criteria: October 27, 2015
• First Posted (Estimate): October 28, 2015

Study Record Updates

• Last Update Posted (Actual): June 14, 2017
• Last Update Submitted That Met QC Criteria: June 10, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: Inflammation; Immunology; Microbiology; Vitamins; Clinical Endocrinology; Respiratory Disorders
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Nutrition Disorders; Genetic Diseases, Inborn; Avitaminosis; Deficiency Diseases; Malnutrition; Pancreatic Diseases; Fibrosis; Vitamin D Deficiency; Cystic Fibrosis; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: IRB00083796