Effectiveness of Paricalcitol in Reducing Parathyroid Hormone (PTH) Levels in X-linked Hypophosphatemic Rickets

Phase 3

Completed

Conditions: Hypophosphatemia, Familial
Hyperparathyroidism

Interventions: Drug: Paricalcitol
Other: Placebo

Registration Number: NCT00417612

Lead Sponsor: Yale University

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 33

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	Paricalcitol	Participants given active drug, paricalcitol (Zemplar), in effort to reduce PTH level
2	Placebo	Participants given placebo capsule to match for comparison

Primary Outcome Measures

Name	Time	Method
Area Under the Curve for Parathyroid Hormone (PTH; Percentage Decrease)	Measured at baseline and Month 12	Mean PTHauc (% decrease) for Paricalcitol (Active Drug) and Placebo from Baseline to Month 12.
Area Under the Curve for Parathyroid Hormone (PTHauc) Measurement	Measured at baseline and Month 12	Mean area under the curve for parathyroid hormone levels (PTHauc) sampled during a 26 hour study period, for Paricalcitol (Active Drug) and Placebo groups at Baseline and Month 12 .
Reduction of Parathyroid Hormone Area Under the Curve (PTHauc) of 20% or Greater	Measured at baseline and Month 12	Clinically significant reduction of Mean PTHauc (% decrease \>/= 20) for Paricalcitol (Active Drug) and Placebo from Baseline to Month 12.

Secondary Outcome Measures

Name	Time	Method
Bone Scan Severity Score	Measured at baseline and Month 12	99-Tc-methylenediphosphonate bone scans were completed and analyzed using the following scale\: Bone scan severity scale with minimum score of 0 and maximum score of 4 (0 is no disease and 4 is greatest severity of disease). Appearance of lumbar spine and the sacroiliac region were used as internal references to which all suspected lesions were compared, and scored as follows: grade 0, normal scan without suspicious lesions grade 1, lesion(s) less intense than normal lumbar spine grade 2, lesion(s) similar in intensity to normal lumbar spine grade 3, lesions more intense than normal lumbar spine but similar to the normal sacroiliac region grade 4, lesions more intense than the normal sacroiliac region. \devised by nuclear medicine radiologist at Yale New Haven Hospital
Static Parameters of Serum Alkaline Phosphatase at Baseline and 1 Year for Paricalcitol and Placebo Arms.	Measured at baseline and Month 12
Percent Change in Urinary Calcium Excretion From Baseline to 1 Year	Measured at baseline and Month 12	Percent change in daily urinary calcium excretion, which is calculated the measurements of the calcium in the subject's 24-hr urine collections done at baseline and at the 1 year timepoints
Serum Calcium	Measured at baseline and Month 12
Serum Intact Fibroblast Growth Factor 23 (FGF23)	Measured at baseline and Month 12
Serum 1,25 (OH)2D	Measured at baseline and Month 12