Treatment of Hypoparathyroidism With Synthetic Human Parathyroid Hormone 1-34

Study Overview
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Brief Summary
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This study has been important in establishing synthetic human parathyroid hormone 1-34 (PTH) as a beneficial treatment for hypoparathyroidism, superior to conventional therapy with calcium and calcitriol. Providing synthetic human parathyroid hormone 1-34 (PTH) to patients who are unresponsive to conventional therapy has enabled severe cases of hypoparathyroidism to be managed effectively with the investigational drug, PTH. The primary goals of this study are to (1) provide long-term PTH therapy to patients who do not respond to conventional therapy; (2) understand the long-term effect of therapeutic PTH replacement on kidney function and bone mineral density; (3) study and track linear growth and bone accrual in children with hypoparathyroidism. (4) determine if subjects reach a normal level of peak bone mass and if the timing of this is comparable to normal age-matched healthy controls.

Detailed Description
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Vitamin D and its analogs, the conventional treatment for hypoparathyroidism, are associated with chronic hypercalciuria due to their lack of calcium-retaining effect in the kidney. This side effect usually occurs even while maintaining the serum calcium in the normal range and may lead to calcium deposition in the kidney (nephrocalcinosis) and renal insufficiency. This study examines the long-term effects of subcutaneous parathyroid hormone (PTH) therapy on calcium metabolism, bone, and renal function. Our previous short-term pilot study comparing subcutaneous PTH with calcitriol demonstrated a significant decrease in urinary calcium excretion during PTH therapy. Based upon these results, we hypothesized that treatment with PTH is more physiologic and provides improved long-term metabolic control. Additionally, treatment with PTH may avoid the adverse side effects on the kidney that are associated with conventional therapy. Patients initially come to the Clinical Center for a two week inpatient evaluation. Subsequent follow-up will occur semiannually on an outpatient basis.

Official Title
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Treatment of Hypoparathyroidism With Synthetic Human Parathyroid Hormone 1-34

Conditions
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Hypoparathyroidism

Intervention / Treatment
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* Drug: Synthetic Human Parathyroid Hormone 1-34
* Drug: Calcitriol & Calcium


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: This study will include patients (ages 17-69) with biochemically confirmed hypoparathyroidism. EXCLUSION CRITERIA Women who are pregnant will be excluded.

Ages Eligible for Study
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Minimum Age: 17 Years
Maximum Age: 69 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PTH 1-34<br>All patients received twice daily synthetic Human Parathyroid Hormone 1-34. | Drug: Synthetic Human Parathyroid Hormone 1-34<br>* twice daily subcutaneous injections<br>* Other names: teriperitide;|
| Experimental: Calcitriol & Calcium<br>All patients received twice daily Calcitriol and Calcium 1000mg divided into four doses daily. | Drug: Calcitriol & Calcium<br>* Twice daily oral calcitriol with 1000 mg Calcium carbonate supplementation<br>* Other names: rocaltrol; 1,25 OH Vitamin D;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Calcium Level | Measurements were taken 1 hour before the morning dose of PTH or, calcitriol and calcium; UOM = mmol/liter, normal range 2.05-2.5. Measurements were obtained on three successive days (three separate measures) semiannually at the NIH CC for each protocol subject. The average data are the average of these three semi-annual data points for each subject which are then averaged across all the semi-annual means for all subjects within each arm over the three years of study. | 3 years | 
| Urine Calcium Excretion Level | Measurements were taken1 hour before the morning dose of PTH or, calcitriol and calcium; UOM = mmol/24 h, normal range 1.25-6.25. Measurements were obtained on three successive days (three separate measures) semiannually at the NIH CC for each protocol subject. The average data are the average of these three semi-annual data points for each subject which are then averaged across all the semi-annual means for all subjects within each arm over the three years of study. | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum 1,25-hydroxyvitamin D Level | Measurements were taken 1 hour before the morning dose of PTH or, calcitriol and calcium; UOM = pg/ml. Measurements were obtained on three successive days (three separate measures) semiannually at the NIH CC for each protocol subject. The average data are the average of these three semi-annual data points for each subject which are then averaged across all the semi-annual means for all subjects within each arm over the three years of study. | 3 years | 
| Serum 25-hydroxyvitamin D Level | Measurements were taken 1 hour before the morning dose of PTH or, calcitriol and calcium; UOM = ng/ml. Measurements were obtained on three successive days (three separate measures) semiannually at the NIH CC for each protocol subject. The average data are the average of these three semi-annual data points for each subject which are then averaged across all the semi-annual means for all subjects within each arm over the three years of study. | 3 years | 
| Serum Magnesium Level | Measurements were taken 1 hour before the morning dose of PTH or, calcitriol and calcium; UOM = mmol/liter, normal range 0.65-1.05. Measurements were obtained on three successive days (three separate measures) semiannually at the NIH CC for each protocol subject. The average data are the average of these three semi-annual data points for each subject which are then averaged across all the semi-annual means for all subjects within each arm over the three years of study. | 3 years | 
| Serum Phosphorus Level | Measurements were taken 1 hour before the morning dose of PTH or, calcitriol and calcium; UOM = mmol/liter, normal range 0.7-1.4. Measurements were obtained on three successive days (three separate measures) semiannually at the NIH CC for each protocol subject. The average data are the average of these three semi-annual data points for each subject which are then averaged across all the semi-annual means for all subjects within each arm over the three years of study. | 3 years | 
| Urinary Creatinine Clearance | Measurements were taken 1 hour before the morning dose of PTH or, calcitriol and calcium; UOM = ml/min, normal range 90-125. Measurements were obtained on three successive days (three separate measures) semiannually at the NIH CC for each protocol subject. The average data are the average of these three semi-annual data points for each subject which are then averaged across all the semi-annual means for all subjects within each arm over the three years of study. | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vitamin D, Hypoparathyroidism, Parathyroid Hormone, Calcium Metabolism, PTH 1-34, Bone