Safety, Efficacy, and Feasibility of High-dose Cholecalciferol in Pediatric Patients With Cystic Fibrosis

Study Overview
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Brief Summary
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Children with Cystic Fibrosis, ages greater than and equal to 36 months of age and less than or equal to 18 years of age, with a 25OHD level less than 30 ng/dL will be asked to participate in this study. Upon consent, they will be given oral cholecalciferol supplementation of 250,000 IU during their next CF clinic visit. The safety will be assessed by measuring a serum calcium level within 1 week of supplementation. Efficacy will be assessed using repeated 25OHD levels throughout the course of 12 months. Feasibility will be assessed with the previous two measures as well as a brief questionnaire administered via telephone within 1 week of supplementation.

Detailed Description
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Children and adults with Cystic Fibrosis (CF) are at risk of developing a vitamin D deficiency or insufficiency, defined as a 2,25-hydroxyvitamin D (25OHD) serum blood level <30 ng/dL. Greater than 85% of people with CF have pancreatic insufficiency, which contributes to poor absorption of fat soluble vitamins in addition to dietary fat. A 25OHD level greater than 30 ng/dL has been described as providing potential improvements to markers of inflammation in adults with CF and is known to improve bone mineral density and prevent bone fractures in all populations, including CF. This study will assess the safety of a one-time high dose of cholecalciferol or vitamin D3 along with the efficacy and feasibility. Children between the ages of 3 years and 18 years (inclusive), with a 25OHD level <30 ng/dL will be provided with a vitamin D3 supplement of 250,000 international units (IU) observed in our CF clinic. We hypothesize that this one-time, oral, high dose of vitamin D3 will safely and effectively raise the 25OHD level to above 30 ng/dL. Safety will be monitored with serum calcium levels 1 week following the dosage, since 25OHD has a half-life of 2-3 weeks and this serum calcium level measurement time-point would be in or near the middle of this range. Feasibility will be measured using a 5-question phone survey 1 week following the dosage (see appendix A - attached). Efficacy will be measured by the 25OHD level itself; if 25OHD levels are found to be between 30-100 ng/dL over the course of the study, the dose will have demonstrated effective in achieving the study's goal. The purpose of this study is to show that 25OHD levels can be safely corrected with a one-time dose of vitamin D3 that can be safely and feasibly provided in the outpatient setting to children with CF.

Official Title
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Safety, Efficacy, and Feasibility of High-dose Cholecalciferol in Pediatric Patients With Cystic Fibrosis

Conditions
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Vitamin D Deficiency

Intervention / Treatment
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* Drug: Treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children with Cystic Fibrosis >36 months of age Serum/blood 25OHD level < 30 ng/dL Ability to provide valid informed consent to be a part of the study Exclusion Criteria: Any history of kidney disease, kidney stones or on dialysis Any history of hypercalcemia Any history of hypercalciuria Pregnancy at time of enrollment Any history of parathyroid disorders Inability to swallow pills by mouth

Ages Eligible for Study
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Minimum Age: 36 Months
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>All patients with a 25OHD level <30 ng/dL will be given 250,000 IU D3 (cholecalciferol) orally at one point in time and during CF clinic. | Drug: Treatment<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of a Single High-dose of Oral Cholecalciferol to Treat a Vitamin D Deficiency in Children With Cystic Fibrosis | The safety of a single high-dose of oral cholecalciferol will be assessed using a serum calcium measurement after administration of treatment. Instances of hypercalcemia will be assessed at 1 week and at 3 months post-treatment. The treatment will be considered to be safe if the serum calcium level does not exceed 14 mg/dL. | 1 week, 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of a Single High-dose of Oral Cholecalciferol in Treating a Vitamin D Insufficiency/Deficiency in Children With Cystic Fibrosis | The efficacy of this treatment will be assessed by the 25OHD level measured after treatment at 3 months, 6 months, and 12 months. The treatment will be considered to be efficacious if the 25OHD level is greater than or equal to 30 ng/dL. | 3 months, 6 months and 12 months | 
| Feasibility of Taking a 1-time High-dose of Cholecalciferol as Assessed by a 5-item Questionnaire | CF patients with a 25OHD level <30 ng/dL who were given 250,000 IU D3. Feasibility will be measured using a 5-item Yes/No questionnaire where item 1 contains 5 sub-item yes/no questions which all relate to the experience of gastrointestinal symptoms. This was administered via telephone 1-week after administration of the treatment. | 1 week |