Clinical trial NCT00001151: Studies With 1,25-Dihydroxycholecalciferol
Official title: Studies With 1,25-Dihydroxycholecalciferol
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Hypocalcemia
Rickets
Keywords: Calciferol
Hypocalcemia
Rickets
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 1999-11-04
Enrollment: 6
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Vitamin D in the diet undergoes changes in the liver and kidneys to several forms. Patients suffering from disorders with Vitamin D resistance are unable to absorb calcium from food. Patients diagnosed with these disorders will be evaluated and treated with high doses of another form of Vitamin D (1,25-dihydroxyvitamin D3). Patients will be monitored and observed throughout the study to avoid experiencing side effects from the medication.

Detailed description: Patients with extreme resistance to 1,25-dihydroxyvitamin D will be evaluated and treated with high doses of 1,25-dihydroxyvitamin D3.

Plan: In previously untreated patients the study will be divided into a control and one or more treatment periods. During the control period, parathyroid status will be assessed by parameters nos. 1\& 2 (below). In previously treated patients maintenance vitamin D will be gradually replaced with 1,25(OH)2D3. This will be accomplished by withdrawal of vitamin D and institution of 1,25(OH)2D3 when the serum calcium shows a downward trend.

1,25(OH)2D3 as 0.25 or 0.5 ug capsules (though IND 20,889) or as a solution of I microgram per ml will be administered orally. In most cases, because of consideration of time and expense, the cooperation of the patient's local physician will be enlisted. The following will be monitored:

1. Serum calcium, phosphorus,alkaline phosphatase,creatinine at twice weekly intervals. After a maintenance dose has been established, this will be decreased to a monthly, and subsequently 3-6 monthly interval.
2. Urine calcium, phosphorus,creatinine and cAMP before therapy and, when appropriate, during therapy.

The dose of 1,25(OH)2D3 will be 0.125 to 50.0 ug/day. Serum calcium will not be allowed to rise above the normal range (2.0 -2.4 mM at NIH). Should hypercalcemia occur, appropriate treatment will be initiated and the drug dosage will be decreased.

Eligibility criteria: * INCLUSION CRITERIA:

Patients with hereditary resistance to calcitrol.

Primary outcomes:
measure: Number of Participants With Normal Serum Calcium Concentrations
timeFrame: 1 year average
Secondary outcomes:
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center, 9000 Rockville Pike
state: Maryland
Study officials:
affiliation: NIDDK/NIH
name: Stephen J Marx, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Marx SJ, Swart EG Jr, Hamstra AJ, DeLuca HF. Normal intrauterine development of the fetus of a woman receiving extraordinarily high doses of 1,25-dihydroxyvitamin D3. J Clin Endocrinol Metab. 1980 Nov;51(5):1138-42. doi: 10.1210/jcem-51-5-1138.
citation: Fraser D, Kooh SW, Kind HP, Holick MF, Tanaka Y, DeLuca HF. Pathogenesis of hereditary vitamin-D-dependent rickets. An inborn error of vitamin D metabolism involving defective conversion of 25-hydroxyvitamin D to 1 alpha,25-dihydroxyvitamin D. N Engl J Med. 1973 Oct 18;289(16):817-22. doi: 10.1056/NEJM197310182891601. No abstract available.
citation: Marx SJ, Spiegel AM, Brown EM, Gardner DG, Downs RW Jr, Attie M, Hamstra AJ, DeLuca HF. A familial syndrome of decrease in sensitivity to 1,25-dihydroxyvitamin D. J Clin Endocrinol Metab. 1978 Dec;47(6):1303-10. doi: 10.1210/jcem-47-6-1303.