Prospective Intervention Study on Vitamin D in Patients With Cystic Fibrosis (D-vitamin)

5-month Pilot Intervention Study on Vitamin D in Patients With Cystic Fibrosis

The vast majority of Cystic Fibrosis (CF) patients worldwide are vitamin D insufficient. There is no evidence of benefit of vitamin D supplementation for CF patients yet. However, descriptive cross-sectional studies suggest that vitamin D might be beneficial with respect to bone health, as well as to the newly described "non-classical" functions of vitamin D such as the potential anti-diabetic and immunomodulatory effects. To prove causation, and to determine which serum vitamin D concentration is optimal for CF patients, vitamin D supplementation interventional studies are needed, such as our trial.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Dietary supplement: Supplementation with vitamin D2/D3

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sweden
  • Stockholm, Sweden, 141 86
    • Stockholm Cystic Fibrosis Center, Karolinska University Hospital Huddinge

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Established diagnosis of cystic fibrosis
• Age 6 years and more
• Serum 25-hydroxy vitamin D concentration at the latest visit < 75 nmol/L

Exclusion Criteria:

• Pregnancy or lactation
• Established diagnosis of CF-related diabetes
• CF-related liver disease
• Status post transplantation (lung, liver or other)
• Long-term corticosteroid treatment per os
• Hypercalcaemia or kidney stones
• Use of tanning beds more often than once a month
• At inclusion, plans to travel to a sunny location for more than 1 week during the study period
• Any known disorders of the endocrine system affecting vitamin D metabolism (hyperparathyroidism, malignancy, advanced renal disease)
• Inclusion into another study testing immunomodulatory substances

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ergocalciferol; Patients younger than 16 years of age are administered 35,000 IU ergocalciferol per week divided into doses 5000 IU per day as a starting dose that is further adjusted by serum 25-hydroxy vitamin D concentration monitoring. Patients 16 or more years of age are administered 50,000 IU ergocalciferol per week divided into doses 7150 IU per day as a starting dose that is further adjusted by serum 25-hydroxy vitamin D concentration monitoring.	Dietary supplement: Supplementation with vitamin D2/D3; Patients younger than 16 years of age are administered 35,000 IU ergo-/chole-calciferol per week divided into doses 5000 IU per day as a starting dose that is further adjusted by serum 25-hydroxy vitamin D concentration monitoring. The intervention time is 3 months, followed by 2-months wash-out period when patients do not take any more extra vitamin D but they are still monitored. Patients 16 or more years of age are administered 50,000 IU ergo-/chole-calciferol per week divided into doses 7150 IU per day as a starting dose that is further adjusted by serum 25-hydroxy vitamin D concentration monitoring.
Experimental: Cholecalciferol; Patients younger than 16 years of age are administered 35,000 IU cholecalciferol per week divided into doses 5000 IU per day as a starting dose that is further adjusted by serum 25-hydroxy vitamin D concentration monitoring. Patients 16 or more years of age are administered 50,000 IU cholecalciferol per week divided into doses 7150 IU per day as a starting dose that is further adjusted by serum 25-hydroxy vitamin D concentration monitoring.	Dietary supplement: Supplementation with vitamin D2/D3; Patients younger than 16 years of age are administered 35,000 IU ergo-/chole-calciferol per week divided into doses 5000 IU per day as a starting dose that is further adjusted by serum 25-hydroxy vitamin D concentration monitoring. The intervention time is 3 months, followed by 2-months wash-out period when patients do not take any more extra vitamin D but they are still monitored. Patients 16 or more years of age are administered 50,000 IU ergo-/chole-calciferol per week divided into doses 7150 IU per day as a starting dose that is further adjusted by serum 25-hydroxy vitamin D concentration monitoring.
No Intervention: Control; Patients continue their ordinary vitamin supplementation without getting extra vitamin D supplements.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum 25-hydroxy vitamin D	This pilot study is primarily designed for establishing effective vitamin D dosing in our specific patient population, and only secondarily designed (and thus, not powered for) for the secondary outcome measures. The results of this study will make it possible for the first time to power the follow-up long-term study for some of the secondary outcome measures followed in this pilot study, some of which might therefore become primary outcome measures in the follow-up study.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Parathyroid hormone (PTH)	As a surrogate marker of bone health	3 months
Inflammatory parameters	Cytokine profiles, antimicrobial peptides, peripheral blood mononuclear cell profiles, immunoglobulines, acute phase markers, sedimentation rate and other	3 months
Infection parameters	Number of days on intravenous antibiotic treatment; number of infectious episodes; number of common cold episodes; relative number of sputum samples positive for pathological bacteria; and other	3 months
Lung function parameters	FEV1, FVC, PEF, FEF25, FEF50, FEF75 and other	3 months
Glucose tolerance parameters	Insulin, C-peptide, glucagon, fasting plasma glucose, HbA1c, 3-hour 75-g oral glucose tolerance test	3 months
Adherence with vitamin D treatment	Semi-quantitative assessment by a questionnaire (thus, a patient-reported outcome)	3 months
Disease-specific quality of life	Assessment using "CFQ-R" questionnaire, specifically designed to measure the quality of life in CF patients	3 months
Plasma calcium	Proportion of patients with albumin-corrected serum calcium increasing to a concentration greater than 2,75 mmol/L in patients with no hypercalcaemia before vitamin D supplementation was started.	3 months
Relative number of patients reaching high abnormal 25(OH)D concentrations	Proportion of patients in the intervention arms reaching 25(OH)D >250 nmol/L	3 months
Proportion of patients reaching toxic 25(OH)D concentrations	Proportion of patients in the intervention arms reaching 25(OH)D >375 nmol/L	3 months
Proportion of patients with suspect hypercalcaemia symptoms	Proportion of patients with suspect hypercalcaemia symptoms in the intervention arms	3 months

Collaborators and Investigators

• Sponsor: Karolinska Institutet
• Collaborators: Region Stockholm

Publications and helpful links

General Publications

• Pincikova T, Paquin-Proulx D, Sandberg JK, Flodstrom-Tullberg M, Hjelte L. Vitamin D treatment modulates immune activation in cystic fibrosis. Clin Exp Immunol. 2017 Sep;189(3):359-371. doi: 10.1111/cei.12984. Epub 2017 May 24.
• Pincikova T, Paquin-Proulx D, Sandberg JK, Flodstrom-Tullberg M, Hjelte L. Clinical impact of vitamin D treatment in cystic fibrosis: a pilot randomized, controlled trial. Eur J Clin Nutr. 2017 Feb;71(2):203-205. doi: 10.1038/ejcn.2016.259. Epub 2016 Dec 14.

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Actual): July 1, 2011
• Study Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: March 23, 2011
• First Submitted That Met QC Criteria: March 23, 2011
• First Posted (Estimated): March 24, 2011

Study Record Updates

• Last Update Posted (Actual): October 15, 2024
• Last Update Submitted That Met QC Criteria: October 11, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Ergocalciferols
• Other Study ID Numbers: 2009/1723-31/1