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Trial registered on ANZCTR


Registration number
ACTRN12609000919213
Ethics application status
Approved
Date submitted
22/10/2009
Date registered
26/10/2009
Date last updated
26/10/2009
Type of registration
Retrospectively registered

Titles & IDs
Public title
Optimizing vitamin D supplementation and sun exposure for breastfed infants in Berlin, Germany
Scientific title
An assessment of the minimal amount of vitamin D supplementation and sun exposure required to provide a sufficient vitamin D status in breastfed infants during their first 6 weeks of life
Secondary ID [1] 1121 0
none
Universal Trial Number (UTN)
U1111-1112-2443
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Vitamin D deficiency 252050 0
Condition category
Condition code
Metabolic and Endocrine 252242 252242 0 0
Metabolic disorders
Diet and Nutrition 252247 252247 0 0
Other diet and nutrition disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Supplementation with either 250 or 500 units of vitamin D3 per day for 6 weeks using oral tablets
Intervention code [1] 241448 0
Treatment: Drugs
Intervention code [2] 241451 0
Prevention
Comparator / control treatment
The two groups are controls for each other. The need of vitamin D supplementation for infants during their first 1.5 years of life in Germany has been established. Having a group without any supplementation was considered as being unethical.
Control group
Dose comparison

Outcomes
Primary outcome [1] 253116 0
25 hydroxy vitamin D levels in plasma
Timepoint [1] 253116 0
1: day 4 after delivery
Primary outcome [2] 253117 0
25 hydroxy vitamin D levels in plasma
Timepoint [2] 253117 0
2: 6 weeks after delivery
Secondary outcome [1] 257988 0
Sun exposure and exposure to ultraviolet B radiation (UVB) specifically. Exposition was measured with continuous dosimetry.
Dosimeters (BioSpor, Germany) consisted of a biological UV-sensitive film, a special filter-optic system and the protective dosimeter casing. The highly sensitive DNA molecules of immobilised spores produce a responsivity profile, which corresponds to that of human skin. The degree of immobilised spores correlates to the exposures of the dosimeter to an adjustable wavelength of solar radiation. The amount of exposures was measured in minimal erythematous doses (MED). One MED equals the amount of radiation that causes first degree erythema or 250 Joule/m2. A clip was provided to attach the dosimeter to clothes. The optimal position for this badge on the infant's clothing was examined during a test phase on puppets. Parents received precise instructions on how to attach the dosimeter on their infant's clothing on their chest.
To complete the analysis, questionnaires were handed out covering surrounding factors influencing sun exposure like ways of sun protection, clothing or type of baby carrier on a daily basis. This information was transformed into a validated score system (sunshine exposure score, Specker, 1985). Higher scores were equivalent to stronger sun exposure.
Detailed meteorological data were obtained from the Institute of Meteorology at the Freie University, Berlin, Germany, for every day of the study period.
Timepoint [1] 257988 0
Continuous measurement from day 4 until 6 weeks after birth (timepoint 1 until timepoint 2)

Eligibility
Key inclusion criteria
Healthy breastfed newborns, term-delivery, appropriate for gestational age (AGA), skin type II or III
Minimum age
No limit
Maximum age
4 Days
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Vitamin D supplementation during pregnancy, drug abuse, premature delivery, highly pigmented skin (>type III), formula feeding

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Personal interview of parents, informed written consent.
Randomisation to either 250 or 500 units of vitamin D3 per day using sealed opaque envelopes.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Choosing odd and even numbers from a sealed opaque envelope (Altman et al, BMJ 1999).
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 2292 0
Germany
State/province [1] 2292 0
Berlin

Funding & Sponsors
Funding source category [1] 243920 0
Other Collaborative groups
Name [1] 243920 0
Northern German Society of Paediatric and Adolescent Medicine
Address [1] 243920 0
Charite, Klinik fuer Allgemeine Paediatrie Augustenburger Platz 1
13354 Berlin
Country [1] 243920 0
Germany
Primary sponsor type
Charities/Societies/Foundations
Name
German Centre for Growth, Development and Preventative Medicine for Children and Adolescents
Address
Klinik fuer Kinder und Jugendmedizin "Lindenhof"
Gotlindestr 2-20
10365 Berlin
Country
Germany
Secondary sponsor category [1] 251278 0
University
Name [1] 251278 0
University of Western Australia
Address [1] 251278 0
School of Paediatrics and Child Health
Princess Margaret Hospital
Roberts Road
Subiaco, WA 6008
Country [1] 251278 0
Australia
Other collaborator category [1] 914 0
Hospital
Name [1] 914 0
Princess Margaret Hospital for Children
Address [1] 914 0
Department of Endocrinology and Diabetes
Roberts Road
Subiaco, WA 6008
Country [1] 914 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 244033 0
Ethics Committee
Ethics committee address [1] 244033 0
Charite University Hospital
Schumann Str.
10117 Berlin
Ethics committee country [1] 244033 0
Germany
Date submitted for ethics approval [1] 244033 0
15/05/1999
Approval date [1] 244033 0
15/10/1999
Ethics approval number [1] 244033 0

Summary
Brief summary
Background: The rate of non-compliance with vitamin D supplementation in countries of Northern latitude is as high as 45%.
Objective: To specify the minimal amount of vitamin D supplementation and sun exposure required to provide a sufficient vitamin D status.
Design: 40 infants (World Health Organisation (WHO) skin types I,II) were recruited in Berlin, Germany (Latitude: 52.5 degrees North) during summer (n=20) and winter (n=20) and randomized into equal groups on either 250 units or 500 units of vitamin D3 per day. Outcome measures were: parameters of vitamin D (25(OH)D) and bone metabolism at delivery and 6 weeks later, sun exposure time, UVB dosimetry and surrounding factors including mother’s diet.
Trial website
n/a
Trial related presentations / publications
1. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357:266-81.
2. Wolpowitz D, Gilchrest BA. The vitamin D questions: how much do you need and how should you get it? J Am Acad Dermatol. 2006;54:301-17.
3. Dratva J, Merten S, Ackermann-Liebrich U. Vitamin D supplementation in Swiss infants. Swiss Med Wkly. 2006;136:473-81.
4. Marjamaki L, Rasanen M, Uusitalo L, et al. Use of vitamin D and other dietary supplements by Finnish children at the age of 2 and 3 years. Int J Vitam Nutr Res. 2004;74:27-34.
5. McGrath J. Does "imprinting" with low prenatal vitamin D contribute to the risk of various adult disorders? Med Hypotheses. 2001;56:367-71.
6. Heaney RP. Functional indices of vitamin D status and ramifications of vitamin D deficiency. Am J Clin Nutr. 2004;80:1706S-9S.
7. Hochberg Z, Bereket A, Davenport M, et al. Consensus development for the supplementation of vitamin D in childhood and adolescence. Horm Res. 2002;58:39-51.
8. Lerch C, Meissner T. Interventions for the prevention of nutritional rickets in term born children. Cochrane Database Syst Rev. 2007:CD006164.
9. Fischer PR, Thacher TD, Pettifor JM, Jorde LB, Eccleshall TR, Feldman D. Vitamin D receptor polymorphisms and nutritional rickets in Nigerian children. J Bone Miner Res. 2000;15:2206-10.
10. Thacher TD, Fischer PR, Pettifor JM, et al. A comparison of calcium, vitamin D or both for nutritional rickets in nigerian children. N Engl J Med. 1999;341:563-8.
11. Glerup H, Mikkelsen K, Poulsen L, et al. Commonly recommended daily intake of vitamin D is not sufficient if sunlight exposure is limited. J Intern Med. 2000;247:260-8.
12. Holick MF, Chen TC. Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr. 2008;87:1080S-6S.
13. Vieth R, Bischoff-Ferrari H, Boucher BJ, et al. The urgent need to recommend an intake of vitamin D that is effective. Am J Clin Nutr. 2007;85:649-50.
14. Fitzpatrick TB, Bolognia JL. Human melanin pigmentation. in: Zeise L, Chedekel MR, Fitzpatrick TB (eds): Melanin: its role in human photoprotection 1995;Overland Park, KS. Valdemar Publishing Co.
15. Altman DG, Andersen PK. Calculating the number needed to treat for trials where the outcome is time to an event. BMJ. 1999;319:1492-5.
16. Gartner LM, Greer FR. Prevention of rickets and vitamin D deficiency: new guidelines for vitamin D intake. Pediatrics. 2003;111:908-10.
17. Specker BL, Valanis B, Hertzberg V, Edwards N, Tsang RC. Sunshine exposure and serum 25-hydroxyvitamin D concentrations in exclusively breast-fed infants. J Pediatr. 1985;107:372-6.
18. Heaney RP, Davies KM, Chen TC, Holick MF, Barger-Lux MJ. Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Am J Clin Nutr. 2003;77:204-10.
19. Hathcock JN, Shao A, Vieth R, Heaney R. Risk assessment for vitamin D. Am J Clin Nutr. 2007;85:6-18.
20. Misselwitz J, Hesse V, Markestad T. Nephrocalcinosis, hypercalciuria and elevated serum levels of 1,25-dihydroxyvitamin D in children. Possible link to vitamin D toxicity. Acta Paediatr Scand. 1990;79:637-43.
21. Markestad T, Hesse V, Siebenhuner M, et al. Intermittent high-dose vitamin D prophylaxis during infancy: effect on vitamin D metabolites, calcium, and phosphorus. Am J Clin Nutr. 1987;46:652-8.
22. Ala-Houhala M. 25-Hydroxyvitamin D levels during breast-feeding with or without maternal or infantile supplementation of vitamin D. J Pediatr Gastroenterol Nutr. 1985;4:220-6.
23. Ladizesky M, Lu Z, Oliveri B, et al. Solar ultraviolet B radiation and photoproduction of vitamin D3 in central and southern areas of Argentina. J Bone Miner Res. 1995;10:545-9.
24. Greer FR. Issues in establishing vitamin D recommendations for infants and children. Am J Clin Nutr. 2004;80:1759S-62.
25. Deutsche Gesellschaft fuer Ernaehrung, Oesterreichische Gesellschaft fuer Ernaehrung, Schweizerische Gesellschaft fuer Ernaehrungsforschung, Schweizerische Gesellschaft fuer Ernaehrung. Referenzwerte fuer die Naehrstoffzufuhr. Umschau Verlag, Frankfurt/M, Germany. 2000.
26. Pittard WB, 3rd, Geddes KM, Hulsey TC, Hollis BW. How much vitamin D for neonates? Am J Dis Child. 1991;145:1147-9.
27. Backstrom MC, Maki R, Kuusela AL, et al. Randomised controlled trial of vitamin D supplementation on bone density and biochemical indices in preterm infants. Arch Dis Child Fetal Neonatal Ed. 1999;80:F161-6.
28. Gartner LM, Greer FR, and the Section on Breastfeeding and Committee on Nutrition AAoP. Prevention of Rickets and Vitamin D Deficiency: New Guidelines for Vitamin D Intake. Pediatrics. 2003;111:908-10.
29. Rajakumar K. Reemerging nutritional rickets: a historical perspective. Arch Pediatr Adolesc Med. 2005;159:335-41.
30. Adams JS, Clemens TL, Parrish JA, Holick MF. Vitamin D synthesis and metabolism after ultraviolet irradiation of normal and vitamin D deficient subjects. N Engl J Med. 1982;306:722-5.
31. Zittermann A, Scheld K, Stehle P. Seasonal variations in vitamin D status and calcium absorption do not influence bone turnover in young women. Eur J Clin Nutr. 1998;52:501-6.
32. Gibbs NK, Young AR, Corbett MF. Personal solar UVR exposure: a method of increasing the reliability of measurements made with film badge dosimeters. Photodermatol. 1984;1:133-6.
33. Greer FR, Marshall S. Bone mineral content, serum vitamin D metabolite concentrations, and ultraviolet B light exposure in infants fed human milk with and without vitamin D2 supplements. J Pediatr. 1989;114:204-12.
34. Kuluncsics Z, Kerekgyarto T, Grof P, Horkay I, Ronto G. Biological UV dosimeters in quality control of tanning tubes. Photochem Photobiol. 2002;76:391-6.
35. Puskeppeleit M, Quintern LE, El Naggar S, et al. Long-Term Dosimetry of Solar UV Radiation in Antarctica with Spores of Bacillus subtilis. Appl Environ Microbiol. 1992;58:2355-9.
36. Quintern LE, Furusawa Y, Fukutsu K, Holtschmidt H. Characterization and application of UV detector spore films: the sensitivity curve of a new detector system provides good similarity to the action spectrum for UV-induced erythema in human skin. J Photochem Photobiol B. 1997;37:158-66.
37. Hoogenboezem T, Degenhart HJ, De Muinck Keizer-Schrama SM, et al. Vitamin D metabolism in breast-fed infants and their mothers. Pediatr Res. 1989;25:623-8.
38. Hesse V, Hoppe S. Stand of rickets prophylaxis-international comparison and new trends in vitamin D dosage. der kinderarzt. 1996;27:1303-13.
39. Baron ED, Stern RS. Correlating skin type and minimum erythema dose. Arch Dermatol. 1999;135:1278-9.
40. Grover SR, Morley R. Vitamin D deficiency in veiled or dark-skinned pregnant women. MJA. 2001;175:251-2.
Public notes

Contacts
Principal investigator
Name 30412 0
Address 30412 0
Country 30412 0
Phone 30412 0
Fax 30412 0
Email 30412 0
Contact person for public queries
Name 13659 0
Dr Aris Siafarikas
Address 13659 0
Princess Margaret Hospital for Children
Department of Endocrinology and Diabetes
Roberts Road
Subiaco, WA 6008
Country 13659 0
Australia
Phone 13659 0
+61893408090
Fax 13659 0
+61893408605
Email 13659 0
Aris.Siafarikas@health.wa.gov.au
Contact person for scientific queries
Name 4587 0
Dr Aris Siafarikas
Address 4587 0
Princess Margaret Hospital for Children
Department of Endocrinology and Diabetes
Roberts Road
Subiaco, WA 6008
Country 4587 0
Australia
Phone 4587 0
+61893408090
Fax 4587 0
+61893408605
Email 4587 0
Aris.Siafarikas@health.wa.gov.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary