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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Thomas Carpenter, Yale University
ClinicalTrials.gov Identifier:
NCT00417612
First received: December 28, 2006
Last updated: October 22, 2014
Last verified: October 2014
  Purpose

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.


Condition Intervention Phase
Hypophosphatemia, Familial
Hyperparathyroidism
Drug: Paricalcitol
Other: Placebo
Phase 3

Study Type: Interventional
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)

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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 ]

Enrollment: 33
Study Start Date: January 2007
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Participants given active drug, paricalcitol (Zemplar), in effort to reduce PTH level
Drug: Paricalcitol
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
Other: Placebo
Placebo sugar pill

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.

  Eligibility

Ages Eligible for Study:   9 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00417612

Locations
United States, Connecticut
Yale University School of Medicine
New Haven, Connecticut, United States, 06520
Sponsors and Collaborators
Yale University
Investigators
Principal Investigator: Thomas O. Carpenter, MD Yale University
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Thomas Carpenter, Professor of Pediatrics, Yale University
ClinicalTrials.gov Identifier: NCT00417612     History of Changes
Other Study ID Numbers: P50 AR054086, P50AR054086, 1P50AR054086-01
Study First Received: December 28, 2006
Results First Received: August 2, 2014
Last Updated: October 22, 2014
Health Authority: United States: Federal Government

Keywords provided by Yale University:
Rickets, Hypophosphatemia
Rickets, Vitamin D-Resistant
Rickets, X-linked hypophosphatemic

Additional relevant MeSH terms:
Familial Hypophosphatemic Rickets
Rickets
Rickets, Hypophosphatemic
Hyperparathyroidism
Hypophosphatemia
Hypophosphatemia, Familial
Avitaminosis
Bone Diseases
Bone Diseases, Metabolic
Calcium Metabolism Disorders
Deficiency Diseases
Endocrine System Diseases
Genetic Diseases, Inborn
Kidney Diseases
Malnutrition
Metabolic Diseases
Metabolism, Inborn Errors
Metal Metabolism, Inborn Errors
Musculoskeletal Diseases
Nutrition Disorders
Parathyroid Diseases
Phosphorus Metabolism Disorders
Renal Tubular Transport, Inborn Errors
Urologic Diseases
Vitamin D Deficiency

ClinicalTrials.gov processed this record on November 27, 2014