Treatment of Hypoparathyroidism With Synthetic Human Parathyroid Hormone 1-34

Hypoparathyroidism Clinical Trial

Official title:

Treatment of Hypoparathyroidism With Synthetic Human Parathyroid Hormone 1-34

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00001304
• Other study ID #: 920011
• Secondary ID: 92-CH-0011
• Status: Completed
• Phase: Phase 2
• First received: November 3, 1999
• Last updated: November 10, 2015
• Start date: October 1991
• Est. completion date: April 2014

Study information

• Verified date: November 2015
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: April 2014
• Est. primary completion date: March 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 17 Years to 69 Years

Eligibility

• INCLUSION CRITERIA:

This study will include patients (ages 17-69) with biochemically confirmed hypoparathyroidism.

EXCLUSION CRITERIA

Women who are pregnant will be excluded.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypoparathyroidism

Intervention

Drug:
• Synthetic Human Parathyroid Hormone 1-34
twice daily subcutaneous injections
• Calcitriol & Calcium
Twice daily oral calcitriol with 1000 mg Calcium carbonate supplementation

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center, 9000 Rockville Pike	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Country where clinical trial is conducted

United States, 

References & Publications (5)

Winer KK, Ko CW, Reynolds JC, Dowdy K, Keil M, Peterson D, Gerber LH, McGarvey C, Cutler GB Jr. Long-term treatment of hypoparathyroidism: a randomized controlled study comparing parathyroid hormone-(1-34) versus calcitriol and calcium. J Clin Endocrinol Metab. 2003 Sep;88(9):4214-20. — View Citation

Winer KK, Sinaii N, Peterson D, Sainz B Jr, Cutler GB Jr. Effects of once versus twice-daily parathyroid hormone 1-34 therapy in children with hypoparathyroidism. J Clin Endocrinol Metab. 2008 Sep;93(9):3389-95. doi: 10.1210/jc.2007-2552. Epub 2008 May 20. — View Citation

Winer KK, Yanovski JA, Cutler GB Jr. Synthetic human parathyroid hormone 1-34 vs calcitriol and calcium in the treatment of hypoparathyroidism. JAMA. 1996 Aug 28;276(8):631-6. — View Citation

Winer KK, Yanovski JA, Sarani B, Cutler GB Jr. A randomized, cross-over trial of once-daily versus twice-daily parathyroid hormone 1-34 in treatment of hypoparathyroidism. J Clin Endocrinol Metab. 1998 Oct;83(10):3480-6. — View Citation

Winer KK, Zhang B, Shrader JA, Peterson D, Smith M, Albert PS, Cutler GB Jr. Synthetic human parathyroid hormone 1-34 replacement therapy: a randomized crossover trial comparing pump versus injections in the treatment of chronic hypoparathyroidism. J Clin Endocrinol Metab. 2012 Feb;97(2):391-9. doi: 10.1210/jc.2011-1908. Epub 2011 Nov 16. Erratum in: J Clin Endocrinol Metab. 2015 Jul;100(7):2800. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No