Clinical trial NCT00949832: Vitamin D and Genetics in Nutritional Rickets
Official title: Vitamin D and Genetics in Nutritional Rickets
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Nutritional Rickets
Keywords: rickets
calcium
vitamin D
nutrition
child
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: Jos University Teaching Hospital
First posted: 2009-07-30
Enrollment: 109
Sex: ALL
Minimum age (years): 6
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is:

1. To compare the response of rickets to calcium with and without vitamin D.
2. To assess whether vitamin D increases calcium absorption in calcium deficiency rickets.
3. To compare the response of children with and without rickets to orally administered vitamin D3 and vitamin D2
4. To identify mutations that influence calcium and vitamin D metabolism among families of children with rickets in Nigeria and Bangladesh.
5. To assess the functional status of the 25-hydroxylase enzyme in families possessing a 25-hydroxylase mutation.

Detailed description: Previous studies of Nigerian children with rickets demonstrated the superiority of calcium over vitamin D in producing healing. It is not known whether the addition of vitamin D to calcium will produce a better response to treatment than calcium alone in Nigerian children. A previous study suggested the possibility that vitamin D may augment the effect of calcium. We will compare the response of rickets to calcium with and without vitamin D. In addition, very little human data clearly demonstrates the effect of supplemental vitamin D on calcium absorption. We will assess whether oral vitamin D increases the already high calcium absorption even further.

Recent published data indicate that the increase in serum 25-hydroxyvitamin D may be more sustained with vitamin D3 than with vitamin D2. We will compare the response of Nigerian children with and without rickets to orally administered vitamin D3 and vitamin D2.

Because nutritional rickets tends to run in families, we will also examine amplified DNA for evidence of mutations that influence calcium and vitamin D metabolism among families of children with rickets in Nigeria and Bangladesh. Families possessing a recently identified 25-hydroxylase mutation will be given oral vitamin D2 and vitamin D3 to determine the functional status of the 25-hydroxylase enzyme.

Eligibility criteria: Inclusion Criteria:

* Clinical features of rickets
* Active rickets on X-ray

Exclusion Criteria:

* Treatment with calcium or vitamin D in preceding 30 days

Primary outcomes:
measure: XR healing of rickets
timeFrame: 6 months
Secondary outcomes:
measure: Alkaline phosphatase
timeFrame: 6 months
measure: Serum calcium
timeFrame: 6 months
measure: 25-hydroxyvitamin D
timeFrame: 6 months
measure: 1,25-dihydroxyvitamin D
timeFrame: 2 weeks
measure: Calcium absorption
timeFrame: 1 week
Other outcomes:
Locations:
city: Jos
country: Nigeria
facility: Jos University Teaching Hospital
state: Plateau
Study officials:
affiliation: Mayo Clinic, Jos University Teaching Hospital
name: Thomas D Thacher, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Thacher TD, Fischer PR, Pettifor JM, Lawson JO, Isichei CO, Reading JC, Chan GM. A comparison of calcium, vitamin D, or both for nutritional rickets in Nigerian children. N Engl J Med. 1999 Aug 19;341(8):563-8. doi: 10.1056/NEJM199908193410803.
citation: Graff M, Thacher TD, Fischer PR, Stadler D, Pam SD, Pettifor JM, Isichei CO, Abrams SA. Calcium absorption in Nigerian children with rickets. Am J Clin Nutr. 2004 Nov;80(5):1415-21. doi: 10.1093/ajcn/80.5.1415.
citation: Thacher TD, Fischer PR, Isichei CO, Pettifor JM. Early response to vitamin D2 in children with calcium deficiency rickets. J Pediatr. 2006 Dec;149(6):840-4. doi: 10.1016/j.jpeds.2006.08.070.
citation: 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 Nov;15(11):2206-10. doi: 10.1359/jbmr.2000.15.11.2206.
citation: Huey SL, Acharya N, Silver A, Sheni R, Yu EA, Pena-Rosas JP, Mehta S. Effects of oral vitamin D supplementation on linear growth and other health outcomes among children under five years of age. Cochrane Database Syst Rev. 2020 Dec 8;12(12):CD012875. doi: 10.1002/14651858.CD012875.pub2.
citation: Thacher TD, Fischer PR, Pettifor JM. Vitamin D treatment in calcium-deficiency rickets: a randomised controlled trial. Arch Dis Child. 2014 Sep;99(9):807-11. doi: 10.1136/archdischild-2013-305275. Epub 2014 Apr 19.