Vitamin D Deficiency, Cystic Fibrosis
Conditions
Keywords
Clinical Endocrinology, Immunology, Inflammation, Microbiology, Respiratory Disorders, Vitamins
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.
Interventions
DIETARY_SUPPLEMENTHigh-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)
OTHERStool 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.
OTHERSputum 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.
OTHERSham Comparator
A placebo capsule taken once a week (manufactured by the same company that makes the Vitamin D supplement).
PROCEDUREBlood 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.
Sponsors
Emory University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Shannon Index | Change from baseline shannon Index at 3 months after initiation of treatment | Sputum microbiota analysis will be measured using this ecological diversity measure. Sputum samples will be collected via a sputum kit. |
| Species Richness Index | Change from baseline Species Richness Index at 3 months after initiation of treatment | Stool microbiota analysis will be measured using this ecological diversity measure. Stool samples will be collected using a stool kit provided to the participant. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Collected via blood draw. |
| 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 | Collected via blood draw. |
| Forced vital capacity (FVC) | Change in Forced vital capacity( FVC) at 3 months after initiation of treatment | 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. |
| 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 | Collected via blood draw. |
| Forced expiratory volume in 1 second (FEV1) | Change in Forced expiratory volume in 1 second( FEV1) at 3 months after initiation of treatment | 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. |
Countries
United States
Outcome results
None listed