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| ID | Type | Description | Link |
|---|---|---|---|
| P50AR054086 | U.S. NIH Grant/Contract | View source | |
| 1P50AR054086-01 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Experimental | Participants given active drug, paricalcitol (Zemplar), in effort to reduce PTH level |
|
| 2 | Placebo Comparator | Participants given placebo capsule to match for comparison |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Paricalcitol | Drug | Paricalcitol given first as a dose of 2 capsules once per day. Dose titration as needed per biochemical results at outpatient visits. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Curve for Parathyroid Hormone (PTHauc) Measurement | 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 . | Measured at baseline and Month 12 |
| Area Under the Curve for Parathyroid Hormone (PTH; Percentage Decrease) | Mean PTHauc (% decrease) for Paricalcitol (Active Drug) and Placebo from Baseline to Month 12. | Measured at baseline and Month 12 |
| Reduction of Parathyroid Hormone Area Under the Curve (PTHauc) of 20% or Greater | Clinically significant reduction of Mean PTHauc (% decrease >/= 20) for Paricalcitol (Active Drug) and Placebo from Baseline to Month 12. | Measured at baseline and Month 12 |
| Measure | Description | Time Frame |
|---|---|---|
| Static Parameters of Serum Alkaline Phosphatase at Baseline and 1 Year for Paricalcitol and Placebo Arms. | Measured at baseline and Month 12 | |
| Serum Calcium | Measured at baseline and Month 12 | |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Thomas O. Carpenter, MD | Yale University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Yale University School of Medicine | New Haven | Connecticut | 06520 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 12386264 | Background | 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. | |
| 2753981 | Background | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Paricalcitol (Active Drug) | Participants given active drug, paricalcitol (Zemplar), in effort to reduce Parathyroid Hormone (PTH) level Paricalcitol: Paricalcitol given first as a dose of 2 capsules once per day. Dose titration as needed per biochemical results at outpatient visits. |
| FG001 | Placebo | Participants given placebo capsule to match for comparison Placebo: Placebo sugar pill |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Paricalcitol (Active Drug) | Participants given active drug, paricalcitol (Zemplar), in effort to reduce PTH level Paricalcitol: Paricalcitol given first as a dose of 2 capsules once per day. Dose titration as needed per biochemical results at outpatient visits. |
| BG001 | Placebo |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Area Under the Curve for Parathyroid Hormone (PTHauc) Measurement | 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 . | Posted | Mean | Standard Deviation | nlEq*26hr/ml | Measured at baseline and Month 12 |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Paricalcitol (Active Drug) | Participants given active drug, paricalcitol (Zemplar), in effort to reduce PTH level Paricalcitol: Paricalcitol given first as a dose of 2 capsules once per day. Dose titration as needed per biochemical results at outpatient visits. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Elevated Serum Creatinine | Renal and urinary disorders |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Thomas O. Carpenter | Yale University School of Medicine | 203-785-6526 | thomas.carpenter@yale.edu |
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| ID | Term |
|---|---|
| D007015 | Hypophosphatemia, Familial |
| D006961 | Hyperparathyroidism |
| D012279 | Rickets |
| D017674 | Hypophosphatemia |
| D063730 | Rickets, Hypophosphatemic |
| D053098 | Familial Hypophosphatemic Rickets |
| ID | Term |
|---|---|
| D015499 | Renal Tubular Transport, Inborn Errors |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
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| ID | Term |
|---|---|
| C084656 | paricalcitol |
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| Placebo | Other | Placebo sugar pill |
|
| Bone Scan Severity Score |
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 |
| Percent Change in Urinary Calcium Excretion From Baseline to 1 Year | 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 | 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 |
| 25029424 | Derived | 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. |
| Protocol Violation |
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| Lost to Follow-up |
|
Participants given placebo capsule to match for comparison Placebo: Placebo sugar pill |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
|
| Secondary | Static Parameters of Serum Alkaline Phosphatase at Baseline and 1 Year for Paricalcitol and Placebo Arms. | Alkaline phosphatase activity was analyzed separately for children (less than 18 years of age) and adults as values varied considerably between these two groups. In other outcome measure modules the paricalcitol group is comprised of 19 participants analyzed which includes adults and children. In this module, the children (2) are their own arm. | Posted | Mean | Standard Deviation | mg/dl | Measured at baseline and Month 12 |
|
|
|
| Secondary | Serum Calcium | Posted | Mean | Standard Deviation | mg/dl | Measured at baseline and Month 12 |
|
|
|
| Secondary | Bone Scan Severity Score | 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 | Posted | Mean | Standard Deviation | units on a scale | Measured at baseline and Month 12 |
|
|
|
| Secondary | Percent Change in Urinary Calcium Excretion From Baseline to 1 Year | 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 | Posted | Mean | Standard Deviation | percent change | Measured at baseline and Month 12 |
|
|
|
| Secondary | Serum Intact Fibroblast Growth Factor 23 (FGF23) | Posted | Mean | 95% Confidence Interval | pg/ml | Measured at baseline and Month 12 |
|
|
|
| Secondary | Serum 1,25 (OH)2D | Posted | Mean | Standard Deviation | pg/ml | Measured at baseline and Month 12 |
|
|
|
| Primary | Area Under the Curve for Parathyroid Hormone (PTH; Percentage Decrease) | Mean PTHauc (% decrease) for Paricalcitol (Active Drug) and Placebo from Baseline to Month 12. | Posted | Number | participants | Measured at baseline and Month 12 |
|
|
|
| Primary | Reduction of Parathyroid Hormone Area Under the Curve (PTHauc) of 20% or Greater | Clinically significant reduction of Mean PTHauc (% decrease >/= 20) for Paricalcitol (Active Drug) and Placebo from Baseline to Month 12. | Posted | Number | percentage of participants | Measured at baseline and Month 12 |
|
|
|
| 0 |
| 22 |
| 2 |
| 22 |
| EG001 | Placebo | Participants given placebo capsule to match for comparison Placebo: Placebo sugar pill | 0 | 11 | 0 | 11 |
| Hypercalcemia | Blood and lymphatic system disorders |
|
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| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D008664 | Metal Metabolism, Inborn Errors |
| D008661 | Metabolism, Inborn Errors |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D010760 | Phosphorus Metabolism Disorders |
| D010279 | Parathyroid Diseases |
| D004700 | Endocrine System Diseases |
| D001851 | Bone Diseases, Metabolic |
| D001847 | Bone Diseases |
| D009140 | Musculoskeletal Diseases |
| D002128 | Calcium Metabolism Disorders |
| D014808 | Vitamin D Deficiency |
| D001361 | Avitaminosis |
| D003677 | Deficiency Diseases |
| D044342 | Malnutrition |
| D009748 | Nutrition Disorders |
|
| >/= 40% |
|