ANZCTR - Registration

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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]

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

Condition category

Condition code

Metabolic and Endocrine

Metabolic disorders

Diet and Nutrition

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]

Treatment: Drugs

Intervention code [2]

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]

25 hydroxy vitamin D levels in plasma

Timepoint [1]

1: day 4 after delivery

Primary outcome [2]

25 hydroxy vitamin D levels in plasma

Timepoint [2]

2: 6 weeks after delivery

Secondary outcome [1]

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]

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

Sex

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

1/01/2000

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]

Germany

State/province [1]

Berlin

Funding & Sponsors

Funding source category [1]

Other Collaborative groups

Name [1]

Northern German Society of Paediatric and Adolescent Medicine

Address [1]

Charite, Klinik fuer Allgemeine Paediatrie Augustenburger Platz 1
13354 Berlin

Country [1]

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]

University

Name [1]

University of Western Australia

Address [1]

School of Paediatrics and Child Health
Princess Margaret Hospital
Roberts Road
Subiaco, WA 6008

Country [1]

Australia

Other collaborator category [1]

Hospital

Name [1]

Princess Margaret Hospital for Children

Address [1]

Department of Endocrinology and Diabetes
Roberts Road
Subiaco, WA 6008

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Ethics Committee

Ethics committee address [1]

Charite University Hospital
Schumann Str.
10117 Berlin

Ethics committee country [1]

Germany

Date submitted for ethics approval [1]

15/05/1999

Approval date [1]

15/10/1999

Ethics approval number [1]

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

Address

Country

Phone

Fax

Contact person for public queries

Name

Dr Aris Siafarikas

Address

Princess Margaret Hospital for Children
Department of Endocrinology and Diabetes
Roberts Road
Subiaco, WA 6008

Country

Australia

Phone

+61893408090

Fax

+61893408605

Aris.Siafarikas@health.wa.gov.au

Contact person for scientific queries

Name

Dr Aris Siafarikas

Address

Princess Margaret Hospital for Children
Department of Endocrinology and Diabetes
Roberts Road
Subiaco, WA 6008

Country

Australia

Phone

+61893408090

Fax

+61893408605

Aris.Siafarikas@health.wa.gov.au

No information has been provided regarding IPD availability

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Dimensions AI	Randomised controlled trial analysing supplementation with 250 versus 500 units of vitamin D3, sun exposure and surrounding factors in breastfed infants	2010	https://doi.org/10.1136/adc.2009.178301

N.B. These documents automatically identified may not have been verified by the study sponsor.

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