Effectiveness of Paricalcitol in Reducing Parathyroid Hormone (PTH) Levels in X-linked Hypophosphatemic Rickets
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||The Role of Parathyroid Hormone in the Pathogenesis of Skeletal Disease in X-linked Hypophosphatemic Rickets (XLH)|
- Area Under the Curve for Parathyroid Hormone (PTHauc) Measurement [ Time Frame: Measured at baseline and Month 12 ] [ Designated as safety issue: No ]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 .
- Area Under the Curve for Parathyroid Hormone (PTH; Percentage Decrease) [ Time Frame: Measured at baseline and Month 12 ] [ Designated as safety issue: No ]Mean PTHauc (% decrease) for Paricalcitol (Active Drug) and Placebo from Baseline to Month 12.
- Reduction of Parathyroid Hormone Area Under the Curve (PTHauc) of 20% or Greater [ Time Frame: Measured at baseline and Month 12 ] [ Designated as safety issue: No ]Clinically significant reduction of Mean PTHauc (% decrease >/= 20) for Paricalcitol (Active Drug) and Placebo from Baseline to Month 12.
- Static Parameters of Serum Alkaline Phosphatase at Baseline and 1 Year for Paricalcitol and Placebo Arms. [ Time Frame: Measured at baseline and Month 12 ] [ Designated as safety issue: No ]
- Serum Calcium [ Time Frame: Measured at baseline and Month 12 ] [ Designated as safety issue: No ]
- Bone Scan Severity Score [ Time Frame: Measured at baseline and Month 12 ] [ Designated as safety issue: No ]
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
- Percent Change in Urinary Calcium Excretion From Baseline to 1 Year [ Time Frame: Measured at baseline and Month 12 ] [ Designated as safety issue: No ]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 Intact Fibroblast Growth Factor 23 (FGF23) [ Time Frame: Measured at baseline and Month 12 ] [ Designated as safety issue: No ]
- Serum 1,25 (OH)2D [ Time Frame: Measured at baseline and Month 12 ] [ Designated as safety issue: No ]
|Study Start Date:||January 2007|
|Study Completion Date:||August 2012|
|Primary Completion Date:||August 2012 (Final data collection date for primary outcome measure)|
Participants given active drug, paricalcitol (Zemplar), in effort to reduce PTH level
Paricalcitol given first as a dose of 2 capsules once per day. Dose titration as needed per biochemical results at outpatient visits.
Other Name: Zemplar
Placebo Comparator: 2
Participants given placebo capsule to match for comparison
Placebo sugar pill
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00417612
|United States, Connecticut|
|Yale University School of Medicine|
|New Haven, Connecticut, United States, 06520|
|Principal Investigator:||Thomas O. Carpenter, MD||Yale University|