Effectiveness of Paricalcitol in Reducing Parathyroid Hormone (PTH) Levels in X-linked Hypophosphatemic Rickets
Effectiveness of Paricalcitol in Reducing Parathyroid Hormone (PTH) Levels in X-linked Hypophosphatemic Rickets
The purpose of this study is to determine the effectiveness of paricalcitol, a form of
 synthetic vitamin D, in lowering parathyroid hormone (PTH) levels and reducing disease
 symptoms in children and adults with X-linked hypophosphatemic (XLH) rickets.
XLH rickets is a rare inherited disorder in which the bones become painfully soft and bend
 easily because of a phosphate deficiency. This genetic defect causes the kidneys to allow
 excretion of an inappropriately high amount of phosphate into the urine. The kidneys are also
 unable to convert vitamin D into a form usable by the body, resulting in inadequate amounts
 of active vitamin D. Because vitamin D is needed to absorb calcium and phosphate from the
 intestine, this deficiency further reduces phosphate levels. Without the sufficient phosphate
 needed for normal bone growth, individuals with XLH rickets typically develop skeletal
 malformations, bone pain, and abnormally bowed legs. Hyperparathyroidism, a condition in
 which the parathyroid glands excrete excess amounts of PTH, also occurs frequently in
 individuals with XLH rickets, and may play a significant role in the skeletal complications
 associated with XLH rickets. The purpose of this study is to determine the effectiveness of
 paricalcitol in lowering PTH levels and reducing disease symptoms in individuals with XLH
 rickets.

 This study will last 12 months. Participants will be randomly assigned to receive either
 paricalcitol or placebo, taken in the form of two pills daily for the duration of the study.
 During a baseline 3-day inpatient hospital stay, participants will undergo a physical exam, a
 cardiac ultrasound, a bone scan, blood collection, and a radiographic skeletal survey. The
 skeletal survey will include x-rays of various body parts. Participants who are 18 years or
 younger will not undergo the radiographic skeletal survey. Study visits for all participants
 will occur every 2 months until the end of the study. These visits will include a physical
 exam, review of disease symptoms, blood and urine collection, and a check of medication
 compliance.
Inclusion Criteria:

 -  Diagnosis of XLH rickets

 -  Fasting serum calcium of 10.7 mg/dl or less

 -  Fasting PTH greater than 40 nleq/ml and less than 120 nleq/ml in the mid-molecule PTH
 assay at screening (upper limit of normal is 25 nleq/ml)

 -  Willing and able to participate in the trial

 -  Taking stable dose of standard therapy for XLH rickets for at least 2 months prior to
 study entry

 -  Concomitant therapy for XLH rickets will not be an exclusion criteria

 -  Parent or guardian willing to provide informed consent, if applicable

 Exclusion Criteria:

 -  Concomitant kidney failure (estimated creatinine clearance less than 60 cc/min or
 serum creatinine greater than 1.5 mg/dl)

 -  Serum 25-hydroxy vitamin D less than 20 ng/ml. Participants meeting this criterion
 will receive vitamin D3 supplementation for 3 months and then be rescreened.

 -  Unable to comply with protocol and appropriate follow-up visits

 -  Treatment with agents that may affect skeletal metabolism, such as glucocorticoids and
 anticonvulsants