Vitamin D Supplementation in Patients With COPD (PRECOVID)

Prevention of Exacerbations in Patients With COPD Through Vitamin D Supplementation: a Randomized Controlled Trial

Vitamin D has an immunomodulatory role. the aim of the present study is to assess the effect of vitamin D supplementation on exacerbation rate of COPD patient with a vitamin D deficiency.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: Placebo; Drug: Vitamin D

Detailed Description

Rationale: Although vitamin D is well known for its function in calcium homeostasis and bone mineralisation, several studies have shown immunomodulatory effects of vitamin D. Vitamin D deficiency is a common problem in patients with COPD..

Objective: To assess the effect of vitamin D supplementation on exacerbation rate in patients with COPD and a vitamin D deficiency.

Study design: Randomized, multi-center, double-blind, placebo-controlled intervention study.

Study population: 240 patients aged 40 years and older with COPD and a vitamin D deficiency (25-hydroxyvitamin D concentration(25OHD)<50 nmol/l) with a COPD exacerbation. An exacerbation is defined as sustained worsening of respiratory symptoms during 48 hours and requiring oral corticosteroid, antibiotic or combination treatment that was initiated by a physician. Respiratory symptoms include at least one of the Anthonisen criteria (increased dyspnoea, sputum volume or purulence). Patients with a severe vitamin D deficiency (25OHD<15 nmol/l), known osteoporosis and/or use of vitamin D supplementation > 400 IU per day will be excluded.

Intervention: Participants will be randomly allocated to receive vitamin D3 16800 IU or placebo orally once a week during 1 year.

Main study parameters/endpoints: The primary endpoint is exacerbation rate.

Follow-up of the study:

Recruitment of participants is more troublesome than expected due to several reasons, more use of vitamin D supplements, higher 250hydroxyvitamin D levels than anticipated, less suitability due to presence other exclusion criteria.

29/8/2017 total number recruited participants is 119

10/7/2018 closure of recruitment, total number recruited participants is 158

• Study Type: Interventional
• Enrollment (Actual): 158
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Leiden, Netherlands
    • Leiden University Medical Center
  • Nijmegen, Netherlands
    • Radboud University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• written informed consent
• aged above 40 years
• GOLD stages II-IV and diagnosis COPD confirmed by a medical doctor.
• minimum of 10 packyears of smoking
• vitamin D deficiency (a serum 25-hydroxyvitamin D lower than 50 nmol/l)
• ability to comply with all study requirements

Exclusion Criteria:

• pregnant or lactating women, or subjects who intend to become pregnant within the study period
• self-reported history of hypercalciemia or nephrolithiasis
• self-reported presence of sarcoidosis
• severe vitamin D deficiency (serum 25-hydroxyvitamin D lower than 15 nmol/l)
• life expectation of less than 6 months on the basis of concurrent disease
• interfering malignant diseases.
• diagnosed osteoporosis
• diagnosed asthma
• diagnosed chronic kidney disease stage 4 or higher (estimated glomerular filtration rate ≤ 29 ml/min/1,73 m2)
• serious mental impairment i.e. preventing to understand the study protocol or comply with the study aim; potentially unreliable patients and those judged by the investigator to be unsuitable for the study
• use of maintenance dose oral corticosteroids
• use of multivitamin supplement or vitamin D supplement which contains more than 400 IU per day
• current participation in a clinical rehabilitation programme

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; placebo	Drug: Placebo
Experimental: Vitamin D; colecalciferol 16.800 IU per week	Drug: Vitamin D; Colecalciferol 16.800 IU per week; Other Names: Colecalciferol, cholecalciferol, vitamin D3

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exacerbation rate	Definition of an exacerbation is according to the Anthonisen criteria	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to first and second exacerbation	Time to first and second exacerbation	1 year
Time to first hospitalisation	Time to first hospitalisation	1 year
FEV1	Forced Expiratory Volume in 1 sec	1 year
IC	Inspiratory capacity	1 year
FEV1/FVC	Forced expiratory volume in 1 sec/ forced vital capacity	1 year
FRC	Functional residual capacity	1 year
RV	Residual volume	1 year
TLC	Total lung capacity	1 year
MIP	Maximal inspiratory pressure	1 year
MEP	Maximal expiratory pressure	1 year
SMWT	Six-minute walk test	1 year
Chair stand test	Chair stand test	1 year
3-meter walking test	3-meter walking test	1 year
Tandem stand test	Tandem stand test	1 year
Total score physical function tests	The sum score of the physical function tests	1 year
Hand grip strength	Hand grip strength	1 year
Quality of life (SGRQ)	QoL by the St George respiratory questionnaire	1 year
Quality of life (SF12)	QoL by the 12 item short form survey	1 year
Anxiety (HADS)	Anxiety by the hospital anxiety and depression scale	1 year
Depression (CESD)	Depression by the center for epidemiologic studies depression scale	1 year
Quality of life (CCQ)	QoL by the Clinical COPD Questionnaire score	1 year
Concentrations of antimicrobial peptides and pro-inflammatory mediators in nasal secretions	AMPs in nasal secretions	1 year
Ex-vivo cytokine production capacity of peripheral blood mononuclear cells and immunophenotyping	cytokine production capacity by PBMCs	1 year
Typing of bacteria and viruses in nasal secretions	Typing of bacteria and viruses in nasal secretions	1 year
Use of corticosteroids	Use of corticosteroids	1 year
Use of antibiotics	Use of antibiotics	1 year
Physical activity (SQUASH)	physical activity by short questionnaire to assess health-enhancing physical activity	1 year

Collaborators and Investigators

• Sponsor: Amsterdam UMC, location VUmc
• Collaborators: Radboud University Medical Center; Leiden University Medical Center
• Investigators: Principal Investigator: Martin den Heijer, Prof, Amsterdam UMC, location VUmc

Publications and helpful links

General Publications

• Rafiq R, Aleva FE, Schrumpf JA, Heijdra YF, Taube C, Daniels JM, Lips P, Bet PM, Hiemstra PS, van der Ven AJ, den Heijer M, de Jongh RT. Prevention of exacerbations in patients with COPD and vitamin D deficiency through vitamin D supplementation (PRECOVID): a study protocol. BMC Pulm Med. 2015 Sep 23;15:106. doi: 10.1186/s12890-015-0101-4.
• Rafiq R, Aleva FE, Schrumpf JA, Daniels JM, Bet PM, Boersma WG, Bresser P, Spanbroek M, Lips P, van den Broek TJ, Keijser BJF, van der Ven AJAM, Hiemstra PS, den Heijer M, de Jongh RT; PRECOVID-study group. Vitamin D supplementation in chronic obstructive pulmonary disease patients with low serum vitamin D: a randomized controlled trial. Am J Clin Nutr. 2022 Aug 4;116(2):491-499. doi: 10.1093/ajcn/nqac083.

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2015
• Primary Completion (Actual): June 26, 2019
• Study Completion (Actual): June 26, 2019

Study Registration Dates

• First Submitted: April 22, 2014
• First Submitted That Met QC Criteria: April 22, 2014
• First Posted (Estimate): April 24, 2014

Study Record Updates

• Last Update Posted (Actual): September 10, 2019
• Last Update Submitted That Met QC Criteria: September 9, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Vitamin D, COPD, immunomodulation, pulmonary function
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Micronutrients; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol; Vitamins; Ergocalciferols
• Other Study ID Numbers: 5.1.13.033