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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: The Role of Parathyroid Hormone in the Pathogenesis of Skeletal Disease in X-linked Hypophosphatemic Rickets (XLH)

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 Summary:

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.


Sponsor: Yale University

Current Primary Outcome:

  • Area Under the Curve for Parathyroid Hormone (PTHauc) Measurement [ Time Frame: 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 .
  • Area Under the Curve for Parathyroid Hormone (PTH; Percentage Decrease) [ Time Frame: Measured at baseline and Month 12 ]
    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 ]
    Clinically significant reduction of Mean PTHauc (% decrease >/= 20) for Paricalcitol (Active Drug) and Placebo from Baseline to Month 12.


Original Primary Outcome:

  • Peak PTH and area under the curve for PTH measurement at baseline and Month 12
  • change in a modified XLH Disease Index (XDI) at Month 12, compared with baseline


Current Secondary Outcome:

  • Static Parameters of Serum Alkaline Phosphatase at Baseline and 1 Year for Paricalcitol and Placebo Arms. [ Time Frame: Measured at baseline and Month 12 ]
  • Serum Calcium [ Time Frame: Measured at baseline and Month 12 ]
  • Bone Scan Severity Score [ Time Frame: 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

  • Percent Change in Urinary Calcium Excretion From Baseline to 1 Year [ Time Frame: 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 Intact Fibroblast Growth Factor 23 (FGF23) [ Time Frame: Measured at baseline and Month 12 ]
  • Serum 1,25 (OH)2D [ Time Frame: Measured at baseline and Month 12 ]


Original Secondary Outcome:

  • Clinical parameters of height and blood pressure
  • Static parameters of serum alkaline phosphatase, CTx (resorption marker), PINP (bone turnover marker), 25-OH vitamin D, FGF7, FRP4 and MEPE (potential disease mediators), urinary calcium excretion, and TMP
  • Diurnal measure including serum Ca, P, PTH, 1,25 vitamin D, and FGF23 (intact and C-terminal)
  • Repeat bone scan
  • Repeat cardiac sonogram
  • Clinical questionnaire, SF-36v2
  • Overall disease score on XDI


Information By: Yale University

Dates:
Date Received: December 28, 2006
Date Started: January 2007
Date Completion:
Last Updated: October 22, 2014
Last Verified: October 2014