Efficacy Study of Vitamin D Supplementation to Meticillin Resistant Staphylococcus Aureus (MRSA) Carriers (D-STAPH)

Vitamin D Supplementation to Persistent Carriers of MRSA - A Double Blind, Randomised Controlled Trial

The purpose of this study is to treat persistent MRSA carriers with vitamin D supplementation during a 12 month to see if the number of MRSA positive patients can be reduced.

Study Overview

• Status: Completed
• Conditions: Vitamin D3 Deficiency; Methicillin Resistant Staphylococcus Aureus
• Intervention / Treatment: Drug: Cholecalciferol; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• Sweden
  • Huddinge
    • Stockholm, Huddinge, Sweden, SE_ 141 86
      • Karolinska University Hospital
  • Solna
    • Stockholm, Solna, Sweden, SE- 171 76
      • Karolinska University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Persistent MRSA-carriers as defined as 2 MRSA-positive bacterial cultures from at least one location, at least 3 months apart and during 3 years prior to inclusion.
2. Men and women aged ≥18-75
3. Signed 'informed consent'
4. Negative pregnancy test (U-hcg) and have to accept the use of adequate anti-conceptive method (contraceptives, hormone/copper-spiral).

Exclusion Criteria:

1. Should not be on vitamin D supplementation at least 6 months prior to inclusion.
2. Serum level of 25-hydroxy vitamin D3 >75 nmol/L
3. Ongoing and continuous antibiotic treatment. The patient should be off antibiotics at least 30 days prior to inclusion
4. Known sarcoidosis
5. Primary or secondary hyperparathyroidism
6. Kidney failure as defined as a normal age-adjusted creatinin.
7. Long term systemic treatment with corticosteroids or other immunosuppressive medication
8. Taking thiazides
9. Hypercalcaemia (verified by a laboratory result younger than 2 month)
10. Ongoing malignancy disorder
11. If plans to leave the Stockholm county within 12 months of inclusion
12. History of kidney stones
13. Pregnancy (ongoing or planned)
14. Breastfeeding women
15. Taking part of another clinical study involving drugs
16. Hypersensitivity to cholecalciferol and/or any of the excipients
17. Other criteria that could jeopardize the study or its intention as judged by the investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Cholecalciferol; 150 patients with MRSA resistent Cholecalciferol 4000 international units (IU)/day for 12 month	Drug: Cholecalciferol; Cholecalciferol 4000 IU/day for 12 months; Other Names: Vigantol Oil (Germany) or Detremin (Sweden)
Placebo Comparator: Sugarpill; 150 patients with MRSA resistent Placebo daily 12 month	Other: Placebo; Placebo (mimic of cholecalciferol) in the same amount and same time frame as Cholecalciferol for 12 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MRSA	The primary endpoint is the decline of MRSA-positive patients during a 12-month period in the treatment groups (vitamin D/Placebo) based on 5 measurements with 3 months interval.	Baseline, 3, 6, 9 and 12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Vitamin D levels in serum	baseline, 3, 6, 9, 12, 18 and 24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patterns of DNA methylation in immune cells	Total DNA from whole blood will be isolated and analysed for methylation patterns using the bisulphite exchange method. Focus will be on methylation in genes related to vitamin D metabolism and immunity, including cytochrome p450 number 24 (CYP24), cytochrome p450 number 27 (CYP27) and cathelicidin antimicrobial peptide (CAMP) genes.	baseline, 3,6, 9, 12, 18 and 24 months
Changes in microflora in the intestinal and nasal tracts		Baseline, 9, 12 and 24 month

Collaborators and Investigators

• Sponsor: Peter Bergman
• Investigators: Principal Investigator: Gudrun Lind, M.D PhD, Karolinska University Hospital, Solna. Department of Infectious Diseases; Principal Investigator: Peter Bergman, M.D PhD, Karolinska University Hospital Huddinge, Department of Infectious Diseases

Publications and helpful links

General Publications

• Hewison M. Antibacterial effects of vitamin D. Nat Rev Endocrinol. 2011 Jun;7(6):337-45. doi: 10.1038/nrendo.2010.226. Epub 2011 Jan 25. Erratum In: Nat Rev Endocrinol. 2011 Aug;7(8):436.
• Bergman P, Norlin AC, Hansen S, Rekha RS, Agerberth B, Bjorkhem-Bergman L, Ekstrom L, Lindh JD, Andersson J. Vitamin D3 supplementation in patients with frequent respiratory tract infections: a randomised and double-blind intervention study. BMJ Open. 2012 Dec 13;2(6):e001663. doi: 10.1136/bmjopen-2012-001663. Print 2012.
• Matheson EM, Mainous AG 3rd, Hueston WJ, Diaz VA, Everett CJ. Vitamin D and methicillin-resistant Staphylococcus aureus nasal carriage. Scand J Infect Dis. 2010 Jul;42(6-7):455-60. doi: 10.3109/00365541003602049.
• Bjorkhem-Bergman L, Torefalk E, Ekstrom L, Bergman P. Vitamin D binding protein is not affected by high-dose vitamin D supplementation: a post hoc analysis of a randomised, placebo-controlled study. BMC Res Notes. 2018 Aug 29;11(1):619. doi: 10.1186/s13104-018-3725-7.
• Bjorkhem-Bergman L, Missailidis C, Karlsson-Valik J, Tammelin A, Ekstrom L, Bottai M, Hammar U, Lindh G, Bergman P. Vitamin D supplementation to persistent carriers of MRSA-a randomized and placebo-controlled clinical trial. Eur J Clin Microbiol Infect Dis. 2018 Sep;37(9):1735-1744. doi: 10.1007/s10096-018-3306-7. Epub 2018 Jun 21.

Helpful Links

• A report on a previous study where vitamin D/Placebo was given to patients with frequent respiratory tract infections.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2014
• Primary Completion (Actual): December 1, 2017
• Study Completion (Actual): December 1, 2017

Study Registration Dates

• First Submitted: June 12, 2014
• First Submitted That Met QC Criteria: June 27, 2014
• First Posted (Estimate): June 30, 2014

Study Record Updates

• Last Update Posted (Actual): January 23, 2018
• Last Update Submitted That Met QC Criteria: January 21, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Staphylococcal Infections; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: D-STAPH-EXT-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED