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Treatment of Hypoparathyroidism With Synthetic Human Parathyroid Hormone 1-34

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Karen K. Winer, M.D., National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00001304
First received: November 3, 1999
Last updated: November 10, 2015
Last verified: November 2015
  Purpose
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 Intervention Phase
Hypoparathyroidism
Drug: Synthetic Human Parathyroid Hormone 1-34
Drug: Calcitriol & Calcium
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Treatment of Hypoparathyroidism With Synthetic Human Parathyroid Hormone 1-34

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Serum Calcium Level [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    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.

  • Urine Calcium Excretion Level [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    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:
  • Serum 1,25-hydroxyvitamin D Level [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    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.

  • Serum 25-hydroxyvitamin D Level [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    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.

  • Serum Magnesium Level [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    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.

  • Serum Phosphorus Level [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    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.

  • Urinary Creatinine Clearance [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    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.


Enrollment: 27
Study Start Date: October 1991
Study Completion Date: April 2014
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.
  Eligibility

Ages Eligible for Study:   17 Years to 69 Years   (Child, Adult, Senior)
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00001304

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:
Responsible Party: Karen K. Winer, M.D., medical officer, National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier: NCT00001304     History of Changes
Other Study ID Numbers: 920011  92-CH-0011 
Study First Received: November 3, 1999
Results First Received: March 12, 2015
Last Updated: November 10, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by 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
Vitamins
Vitamin D
Calcitriol
Calcium, Dietary
Hormones
Micronutrients
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Calcium Channel Agonists
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Vasoconstrictor Agents

ClinicalTrials.gov processed this record on December 07, 2016