Treatment of Hypoparathyroidism With Synthetic Human Parathyroid Hormone 1-34

• ClinicalTrials.gov Identifier: NCT00001304
• Recruitment Status: Completed
• First Posted: November 4, 1999
• Results First Posted: December 15, 2015
• Last Update Posted: December 15, 2015
• Sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Information provided by (Responsible Party): Karen K. Winer, M.D., National Institutes of Health Clinical Center (CC)

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Hypoparathyroidism	Drug: Synthetic Human Parathyroid Hormone 1-34; Drug: Calcitriol & Calcium	Phase 2

Detailed 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 27 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Treatment of Hypoparathyroidism With Synthetic Human Parathyroid Hormone 1-34
• Study Start Date: October 1991
• Actual Primary Completion Date: March 2014
• Actual Study Completion Date: April 2014

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Serum Calcium Level [ Time Frame: 3 years ]
   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.
2. Urine Calcium Excretion Level [ Time Frame: 3 years ]
   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.

Secondary Outcome Measures :

1. Serum 1,25-hydroxyvitamin D Level [ Time Frame: 3 years ]
   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.
2. Serum 25-hydroxyvitamin D Level [ Time Frame: 3 years ]
   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. Serum Magnesium Level [ Time Frame: 3 years ]
   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.
4. Serum Phosphorus Level [ Time Frame: 3 years ]
   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.
5. Urinary Creatinine Clearance [ Time Frame: 3 years ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 17 Years to 69 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

• INCLUSION CRITERIA:

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

EXCLUSION CRITERIA

Women who are pregnant will be excluded.

Contacts and Locations

Locations

United States, Maryland

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, United States, 20892

Sponsors and Collaborators

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

Investigators

• Principal Investigator: Karen K Winer, M.D.; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

More Information

Publications:

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.

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. doi: 10.1210/jcem.83.10.5185.

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.

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. doi: 10.1210/jc.2002-021736.

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.

• Responsible Party: Karen K. Winer, M.D., medical officer, National Institutes of Health Clinical Center (CC)
• ClinicalTrials.gov Identifier: NCT00001304
• Other Study ID Numbers: 920011; 92-CH-0011 ( Other Grant/Funding Number: NIH Clinical Center_NICHD )
• First Posted: November 4, 1999
• Results First Posted: December 15, 2015
• Last Update Posted: December 15, 2015
• Last Verified: November 2015

Keywords provided by Karen K. Winer, M.D., National Institutes of Health Clinical Center (CC):

Hypoparathyroidism; Parathyroid Hormone; Vitamin D; Calcium Metabolism; PTH 1-34; Bone

Additional relevant MeSH terms:

Hypoparathyroidism; Parathyroid Diseases; Endocrine System Diseases; Vitamin D; Calcitriol; Calcium; Parathyroid Hormone; Hormones; Vitamins; Micronutrients; Physiological Effects of Drugs; Calcium-Regulating Hormones and Agents; Bone Density Conservation Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Calcium Channel Agonists; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Vasoconstrictor Agents