- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00417612
Effectiveness of Paricalcitol in Reducing Parathyroid Hormone (PTH) Levels in X-linked Hypophosphatemic Rickets
The Role of Parathyroid Hormone in the Pathogenesis of Skeletal Disease in X-linked Hypophosphatemic Rickets (XLH)
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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Connecticut
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New Haven, Connecticut, United States, 06520
- Yale University School Of Medicine
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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 Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 1
Participants given active drug, paricalcitol (Zemplar), in effort to reduce PTH level
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Paricalcitol given first as a dose of 2 capsules once per day.
Dose titration as needed per biochemical results at outpatient visits.
Other Names:
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Placebo Comparator: 2
Participants given placebo capsule to match for comparison
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Placebo sugar pill
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Area Under the Curve for Parathyroid Hormone (PTHauc) Measurement
Time Frame: Measured at baseline and Month 12
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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 .
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Measured at baseline and Month 12
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Area Under the Curve for Parathyroid Hormone (PTH; Percentage Decrease)
Time Frame: Measured at baseline and Month 12
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Mean PTHauc (% decrease) for Paricalcitol (Active Drug) and Placebo from Baseline to Month 12.
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Measured at baseline and Month 12
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Reduction of Parathyroid Hormone Area Under the Curve (PTHauc) of 20% or Greater
Time Frame: Measured at baseline and Month 12
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Clinically significant reduction of Mean PTHauc (% decrease >/= 20) for Paricalcitol (Active Drug) and Placebo from Baseline to Month 12.
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Measured at baseline and Month 12
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Static Parameters of Serum Alkaline Phosphatase at Baseline and 1 Year for Paricalcitol and Placebo Arms.
Time Frame: Measured at baseline and Month 12
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Measured at baseline and Month 12
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Serum Calcium
Time Frame: Measured at baseline and Month 12
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Measured at baseline and Month 12
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Bone Scan Severity Score
Time Frame: Measured at baseline and Month 12
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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 |
Measured at baseline and Month 12
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Percent Change in Urinary Calcium Excretion From Baseline to 1 Year
Time Frame: Measured at baseline and Month 12
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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
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Measured at baseline and Month 12
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Serum Intact Fibroblast Growth Factor 23 (FGF23)
Time Frame: Measured at baseline and Month 12
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Measured at baseline and Month 12
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Serum 1,25 (OH)2D
Time Frame: Measured at baseline and Month 12
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Measured at baseline and Month 12
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Thomas O. Carpenter, MD, Yale University
Publications and helpful links
General Publications
- Brown AJ, Dusso AS, Slatopolsky E. Vitamin D analogues for secondary hyperparathyroidism. Nephrol Dial Transplant. 2002;17 Suppl 10:10-9. doi: 10.1093/ndt/17.suppl_10.10.
- McElduff A, Posen S. Parathyroid hormone sensitivity in familial X-linked hypophosphatemic rickets. J Clin Endocrinol Metab. 1989 Aug;69(2):386-9. doi: 10.1210/jcem-69-2-386.
- Carpenter TO, Olear EA, Zhang JH, Ellis BK, Simpson CA, Cheng D, Gundberg CM, Insogna KL. Effect of paricalcitol on circulating parathyroid hormone in X-linked hypophosphatemia: a randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab. 2014 Sep;99(9):3103-11. doi: 10.1210/jc.2014-2017. Epub 2014 Jul 16.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Metabolic Diseases
- Kidney Diseases
- Urologic Diseases
- Endocrine System Diseases
- Nutrition Disorders
- Genetic Diseases, Inborn
- Musculoskeletal Diseases
- Parathyroid Diseases
- Avitaminosis
- Deficiency Diseases
- Malnutrition
- Bone Diseases
- Metabolism, Inborn Errors
- Bone Diseases, Metabolic
- Renal Tubular Transport, Inborn Errors
- Calcium Metabolism Disorders
- Metal Metabolism, Inborn Errors
- Phosphorus Metabolism Disorders
- Vitamin D Deficiency
- Hyperparathyroidism
- Rickets
- Familial Hypophosphatemic Rickets
- Hypophosphatemia
- Rickets, Hypophosphatemic
- Hypophosphatemia, Familial
Other Study ID Numbers
- 0607001636
- P50AR054086 (U.S. NIH Grant/Contract)
- 1P50AR054086-01 (U.S. NIH Grant/Contract)
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