Autosomal Dominant Hypophosphatemic Rickets
Conditions
Keywords
ADHR, Rickets, Hypophosphatemia
Brief summary
The purpose of the study is to gain a better understanding of the effect of iron on fibroblast growth factor 23 (FGF23) in the inherited disorder, autosomal dominant hypophosphatemic rickets (ADHR). ADHR is an inherited disorder in which the body makes too much FGF 23 and causes low blood phosphorus levels and bone problems such as rickets (bowed legs in children) or bone pain and weakness in adults. This study is to test whether or not giving iron helps correct the high FGF23 and there by correcting the phosphate problem.
Detailed description
Iron will be provided in an open label treatment to all enrolled subjects. Iron levels will be monitored in blood and doses adjusted with the target of getting the iron levels to or a little above 100 mcg/dl. The study will look to see if there is a decrease of FGF23 level. It will also look at how long does it take to decrease the level of FGF 23 and how long it takes for the serum and urine phosphate to normalize.
Interventions
DIETARY_SUPPLEMENTIron
All subjects will receive iron supplementation based on iron levels in the blood
Sponsors
Indiana University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
25 Months to No maximum
Healthy volunteers
No
Inclusion criteria
* FGF Mutation in either Arginine 176 or arginine 179 * able and willing to provide consent or have a parent that is able/willing to consent, if a minor * either serum iron \<50mcg/dl (regardless of phosphate or intact FGF23 concentration); or iron between 500 and 100mcg/dl with serum phosphorus value below 3.0mg/dl for adults or less than or equal to 0.5 mg/dl the lower limit of normal for age in children and intact FGF23 about 30pg/ml * age \>2 years * May be receiving treatment with phosphate and calcitriol, but must be willing to undergo dose adjustments by the investigators if iron resolves the phosphate wasting defect.
Exclusion criteria
* malignancy within the last 5 years, except treated squamous or basal cell skin carcinoma * terminal illness/hospice. * severe end-organ disease, e.g. cardiovascular, pulmonary, etc, which may limit ability to complete study. estimated GFR \<45ml/min/1.73m2, calculated using MDRD formula for adults or modified Schwartz equation for children * pregnancy or plan on becoming pregnant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Does increasing serum iron concentrations above 100 mcg/dl in patients with ADHR result in a decrease in intact FGF23. | FGF23 will be measured at 1, 2, 3, 6, 9, and 12 months | Perform a pilot study in ADHR patients with low serum iron concentrations (defined below) to determine if increasing serum iron concentrations above 100 mcg/dl results in a decrease in intact FGF23 (primary endpoint) and C-terminal FGF23 concentrations by at least 20% and normalizes serum phosphorus and TMP/GFR (tubular maximum phosphate reabsorption/ glomerular filtration rate) within 6 months of attaining goal iron concentrations. |
Countries
United States
Outcome results
None listed