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

• Sponsor: Johns Hopkins All Children's Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT02613884
• Collaborator: (none)
• Enrollment: 26
• Location: 1
• Arm: 1
• Duration (Months): 36.8
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Vitamin D Deficiency	Drug: Treatment	Phase 2

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 26 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Safety, Efficacy, and Feasibility of High-dose Cholecalciferol in Pediatric Patients With Cystic Fibrosis
• Study Start Date: Nov 1, 2016
• Actual Primary Completion Date: Nov 25, 2019
• Actual Study Completion Date: Nov 25, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment 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

Outcome Measures

Primary Outcome Measures

1. Safety of a Single High-dose of Oral Cholecalciferol to Treat a Vitamin D Deficiency in Children With Cystic Fibrosis [1 week, 3 months]

   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.

Secondary Outcome Measures

1. Efficacy of a Single High-dose of Oral Cholecalciferol in Treating a Vitamin D Insufficiency/Deficiency in Children With Cystic Fibrosis [3 months, 6 months and 12 months]

   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.

2. Feasibility of Taking a 1-time High-dose of Cholecalciferol as Assessed by a 5-item Questionnaire [1 week]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 36 Months to 18 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Johns Hopkins All Children's Hospital	Saint Petersburg	Florida	United States	33701

Sponsors and Collaborators

• Johns Hopkins All Children's Hospital

Investigators

• Principal Investigator: Deanna Green, MD, Johns Hopkins All Children's Hospital

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 20, 2016

More Information

Publications

None provided.

• Responsible Party: Johns Hopkins All Children's Hospital
• ClinicalTrials.gov Identifier: NCT02613884
• Other Study ID Numbers: 128487
• First Posted: Nov 25, 2015
• Last Update Posted: Feb 3, 2021
• Last Verified: Jan 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Additional relevant MeSH terms: Cystic Fibrosis; Vitamin D Deficiency

Study Results

Participant Flow

Recruitment Details	Pediatric patients with Cystic fibrosis (CF) and greater than or equal to 36 months of age with a serum/blood 25OHD level < 30 ng/mL were recruited to participate in the study.

Arm/Group Title	Treatment With High-Dose D3
Arm/Group Description	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.
Period Title: Overall Study
STARTED	26
Safety Endpoint 1	26
Feasibility Questionnaire	26
Safety Endpoint 2	26
Efficacy Endpoint 1	25
Efficacy Timepoint 2	25
Efficacy Timepoint 3	24
COMPLETED	24
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Treatment
Arm/Group Description	All patients with a 25OHD level <30 ng/dL & given 250,000 IU D3 (cholecalciferol).
Overall Participants	26
Age (Count of Participants)
<=18 years	26 100%
Between 18 and 65 years	0 0%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	13.46 (3.18)
Sex: Female, Male (Count of Participants)
Female	15 57.7%
Male	11 42.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	0 0%
More than one race	0 0%
Unknown or Not Reported	26 100%
Region of Enrollment (Count of Participants)
United States	26 100%
25-hydroxycholecalciferol (25OHD) level (ng/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ng/mL]	22.69 (4.75)
Pancreatic Sufficient (Count of Participants)
Yes	3 11.5%
No	23 88.5%
Taking additional vitamin D at enrollment (Count of Participants)
Yes	18 69.2%
No	8 30.8%
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	20.09 (3.25)
BMI Percentile (percentile) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentile]	56.22 (24.21)

Outcome Measures

1. Primary Outcome

Title	Safety of a Single High-dose of Oral Cholecalciferol to Treat a Vitamin D Deficiency in Children With Cystic Fibrosis
Description	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.
Time Frame	1 week, 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment With High-Dose D3
Arm/Group Description	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.
Measure Participants	26
Serum Calcium 1-week	9.57 (0.32)
Serum Calcium 3-month	9.47 (0.41)

2. Secondary Outcome

Title	Efficacy of a Single High-dose of Oral Cholecalciferol in Treating a Vitamin D Insufficiency/Deficiency in Children With Cystic Fibrosis
Description	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.
Time Frame	3 months, 6 months and 12 months

Outcome Measure Data

Analysis Population Description

26 participants were enrolled and given the treatment (250,000 IU D3) and assessed for the primary outcome measure. At the 3-month outcome measure, one participant had passed away, so 25 participants were included in the analysis. At the 12-month outcome measure, one additional participant was lost to follow-up, so 24 participants were included for analysis.

Arm/Group Title	Treatment
Arm/Group Description	All patients with a 25OHD level <30 ng/dL & given 250,000 IU D3 (cholecalciferol).
Measure Participants	25
25OHD level at 3 months	26
25OHD level at 6 months	30
25OHD level at 12 months	27

3. Secondary Outcome

Title	Feasibility of Taking a 1-time High-dose of Cholecalciferol as Assessed by a 5-item Questionnaire
Description	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.
Time Frame	1 week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment With High-Dose D3
Arm/Group Description	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.
Measure Participants	26
No	24 92.3%
Yes	2 7.7%
No	26 100%
Yes	0 0%
No	23 88.5%
Yes	3 11.5%
No	25 96.2%
Yes	1 3.8%
No	24 92.3%
Yes	2 7.7%
No	23 88.5%
Yes	3 11.5%
No	24 92.3%
Yes	2 7.7%
No	0 0%
Yes	26 100%
No	0 0%
Yes	26 100%
No	0 0%
Yes	26 100%

Adverse Events

Time Frame	12 months
Arm/Group Title	Treatment
Arm/Group Description	All patients with a 25OHD level <30 ng/dL & given 250,000 IU D3 (cholecalciferol).
All Cause Mortality
	Treatment
	Affected / at Risk (%)	# Events
Total	1/26 (3.8%)
Serious Adverse Events
	Treatment
	Affected / at Risk (%)	# Events
Total	4/26 (15.4%)
Respiratory, thoracic and mediastinal disorders
Lung infection	1/26 (3.8%)	1
Decreased lung function and weight loss	2/26 (7.7%)	2
Bronchopneumonia exacerbation	1/26 (3.8%)	1
Other (Not Including Serious) Adverse Events
	Treatment
	Affected / at Risk (%)	# Events
Total	15/26 (57.7%)
Gastrointestinal disorders
Diarrhea	3/26 (11.5%)	3
Stomach ache	3/26 (11.5%)	3
Increased burping	2/26 (7.7%)	2
Nausea	2/26 (7.7%)	2
Heart burn/Reflux	2/26 (7.7%)	2
Constipation	1/26 (3.8%)	1
General disorders
Elevated phosphorus level	4/26 (15.4%)	4
Elevated PTH	1/26 (3.8%)	1
Elevated calcium level	1/26 (3.8%)	1
Respiratory, thoracic and mediastinal disorders
Lung infection	2/26 (7.7%)	2
Hypoxemia	1/26 (3.8%)	1
Sinus Infection	1/26 (3.8%)	1
Increased cough	1/26 (3.8%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.