Vitamin D and Microbiota in Cystic Fibrosis

NCT02589444 | Completed

• 1 other identifier: IRB00083796
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Vitamin D Deficiency; Cystic Fibrosis

Keywords

Clinical Endocrinology; Immunology; Inflammation; Microbiology; Respiratory Disorders; Vitamins

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (5)

• 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

  At baseline and 3 months after initiation of treatment

• Forced expiratory volume in 1 second (FEV1)

  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.

  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

  At baseline and 3 months after initiation of treatment

• Forced vital capacity (FVC)

  Change in Forced vital capacity( FVC) at 3 months after initiation of treatment

Study Arms (3)

Participants with vitamin D deficiency - treatment group

EXPERIMENTAL

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; Other: Stool Sample; Other: Sputum Sample; Procedure: Blood draw

Participants with vitamin D deficiency - placebo group

SHAM COMPARATOR

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; Other: Sputum Sample; Other: Sham Comparator; Procedure: Blood draw

Participants without vitamin D deficiency

OTHER

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; Other: Sputum Sample; Procedure: Blood draw

Interventions

High-Dose Vitamin D3 DIETARY_SUPPLEMENT

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)

Also known as: Cholecalciferol

Participants with vitamin D deficiency - treatment group

Stool Sample OTHER

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.

Participants with vitamin D deficiency - placebo group; Participants with vitamin D deficiency - treatment group; Participants without vitamin D deficiency

Sputum Sample OTHER

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.

Participants with vitamin D deficiency - placebo group; Participants with vitamin D deficiency - treatment group; Participants without vitamin D deficiency

Sham Comparator OTHER

A placebo capsule taken once a week (manufactured by the same company that makes the Vitamin D supplement).

Also known as: Placebo

Participants with vitamin D deficiency - placebo group

Blood draw PROCEDURE

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.

Participants with vitamin D deficiency - placebo group; Participants with vitamin D deficiency - treatment group; Participants without vitamin D deficiency

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Emory University: lead

Study Sites (1)

Emory Clinic

Atlanta, Georgia, 30322, United States

Location

Related Publications (1)

• 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.

  PMID: 29161417 DERIVED

MeSH Terms

Conditions

Vitamin D Deficiency; Cystic Fibrosis; Inflammation; Respiration Disorders

Interventions

Cholecalciferol; Blood Specimen Collection

Condition Hierarchy (Ancestors)

Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Vin Tangpricha, MD/PhD

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: October 20, 2015
• First Posted: October 28, 2015
• Study Start: December 1, 2015
• Primary Completion: February 1, 2017
• Study Completion: April 1, 2017
• Last Updated: June 14, 2017

Record last verified: 2017-06

Locations

US (1)