Clinical trial NCT02589444: Vitamin D and Microbiota in Cystic Fibrosis
Official title: Pilot Study Evaluating the Role of Vitamin D Repletion on Gut and Lung Microbiota in Cystic Fibrosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Vitamin D Deficiency
Cystic Fibrosis
Keywords: Clinical Endocrinology
Immunology
Inflammation
Microbiology
Respiratory Disorders
Vitamins
Lead sponsor: Emory University
Sponsor class: OTHER
First posted: 2015-10-28
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Shannon Index
timeFrame: Change from baseline shannon Index at 3 months after initiation of treatment
measure: Species Richness Index
timeFrame: Change from baseline Species Richness Index at 3 months after initiation of treatment
Secondary outcomes:
measure: 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
timeFrame: At baseline and 3 months after initiation of treatment
measure: Forced expiratory volume in 1 second (FEV1)
timeFrame: Change in Forced expiratory volume in 1 second( FEV1) at 3 months after initiation of treatment
measure: Measures of plasma oxidative stress by assessing plasma aminothiol concentrations (glutathione, glutathione disulfide, cysteine, cystine) and their redox potentials.
timeFrame: At baseline and 3 months after initiation of treatment
measure: Measures of inflammation by assessing plasma IL-6, TNF-alpha, MCP-1, and IL-8 concentrations
timeFrame: At baseline and 3 months after initiation of treatment
measure: Forced vital capacity (FVC)
timeFrame: Change in Forced vital capacity( FVC) at 3 months after initiation of treatment
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory Clinic
state: Georgia
Study officials:
affiliation: Emory University
name: Vin Tangpricha, MD/PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.