Comparing Pump With Subcutaneous Injection Delivery of PTH 1-34 in the Management of Chronic Hypoparathyroidism

Comparing Pump vs. Subcutaneous Injection Delivery of PTH 1-34 in the Management of Chronic Hypoparathyroidism

This randomized crossover study will evaluate the safety, efficacy, and pharmacodynamics of synthetic human PTH 1-34 (PTH) delivered by an insulin pump (omnipod) compared with twice- daily subcutaneous injections. We predict pump delivery of PTH will simultaneously normalize blood and urine mineral levels with minimal or no fluctuations throughout the day, thus resulting in a more physiologic pharmacodynamic profile because this method of delivery mimics normal parathyroid gland function. Furthermore, we hypothesize that pump therapy will require lower PTH doses and will normalize markers of bone turnover. We anticipate the improved metabolic control when PTH is delivered by pump will be evident both in adults with surgically induced hypoparathyroidism and in children with more severe forms of hypoparathyroidism where there is an unmet need for improved therapy.

Study Overview

• Status: Completed
• Conditions: Hypocalcemia; Hypoparathyroidism; Autosomal Dominant Hypocalcemia Type 1 (ADH1); Autoimmune Polyendocrine Syndrome Type 1
• Intervention / Treatment: Drug: Synthetic Human Parathyroid Hormone 1-34 pump

Detailed Description

Prior studies (92-CH-0011) have been important in establishing synthetic human parathyroid hormone 1-34 (PTH) as a beneficial treatment for hypoparathyroidism, superior to conventional therapy with calcitriol and calcium. We are conducting a randomized crossover study comparing PTH delivered by an insulin pump vs twice-daily subcutaneous injections. We hypothesize that pump delivery of PTH 1-34, compared to injections, will provide smoother metabolic control of serum mineral levels with minimal fluctuations, normalization of urine mineral excretion and markers of bone turnover. The two arms will be divided into an inpatient and an outpatient phase. There will be three inpatient admissions at baseline, 3 months and 6 months which are separated by two 3-month outpatient periods.

Patients between 10 and 70 years of age with chronic hypoparathyroidism for at least 1 year may be eligible for participation in this study. After the baseline evaluation, conventional therapy (calcitriol and calcium supplements) is discontinued and PTH delivered by an insulin pump (Omnipod) or by twice-daily subcutaneous injections is initiated, depending on randomization sequence. PTH is provided for the study (Clinical Center Pharmacy) in 200 mcg/mL vials. The initial PTH daily dose is 0.2 μg/kg/day for pump therapy and 0.5 μg/kg/day for the twice-daily injection therapy. Inpatient admissions consist of daily (early morning) blood collections for mineral levels, 1,25 OH vitamin D, and markers of bone turnover along with 24-h urine excretion measures of minerals to determine the optimal individualized dose. Titration of PTH dose continues during the outpatient phase with blood labs measured on a weekly basis and less often, when frequent changes are considered unnecessary. Study participants will cross over to the alternate PTH delivery method (PTH delivered by pump vs. injections) at the conclusion of the initial 3-month treatment period. At the conclusion of the third hospital admission, patients will return to the therapy they were receiving at study entry.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institutes of Health Clinical Center, 9000 Rockville Pike

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years to 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

• INCLUSION CRITERIA:

This study will include up to 24 patients of both genders (ages 7-70) with biochemically confirmed chronic hypoparathyroidism of at least one year duration. We will recruit adults with post-surgical hypoparathyroidism and children with genetic forms of hypoparathyroidism including autoimmune polyendocrine syndrome type 1 (APS-1) or hypocalcemia due to an activating mutation of the calcium sensing receptor.

EXCLUSION CRITERIA:

Subjects who meet any of the following criteria are not eligible for study entry:

• Presence of significant hepatic or kidney disease
• Pregnancy
• Patients who are calcium infusion dependent.
• Seizure disorder requiring antiepileptic medications

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: PTH 1-34 delivered through pump, then subcutaneous injection; Children and young adults with genetic forms of hypoparathyroidism and adults with postsurgical hypoparathyroidism, ages 7 to 70 years, received Synthetic Human Parathyroid Hormone 1-34 (PTH) delivered through an insulin pump. The first admission included measures of blood and urine minerals for dose titration. The initial PTH dose was 0.2 μg/kg/day. After inpatient and outpatient blood and urine monitoring, the final mean dose at 13 weeks was 0.32 mcg/kg/day for children and 0.17 mcg/kg/day for adults. At the conclusion of the initial three-month study period, patients crossed over to the opposite arm (PTH by pump vs injections) for the final 3 months with the identical monitoring protocol.	Drug: Synthetic Human Parathyroid Hormone 1-34 pump; comparing two delivery modalities for PTH: insulin pump versus subcutaneous injections.
Active Comparator: PTH 1-34 subcutaneous injection, then delivered through pump; Children with genetic forms of hypoparathyroidism and adults with postsurgical hypoparathyroidism receive synthetic human parathyroid hormone 1-34 (PTH) delivered by twice-daily subcutaneous injections. The initial PTH total daily dose of 0.5 μg/kg/day. After inpatient and outpatient blood and urine monitoring, the final mean dose at 13 weeks was 0.85 mcg/kg/day for children and 0.47 mcg/kg/day for adults. At the conclusion of the first three-month study period, patients crossed over to the opposite drug-delivery arm (PTH delivered by pump vs injections) and entered the second 3-month study period, with the identical monitoring protocol.	Drug: Synthetic Human Parathyroid Hormone 1-34 pump; comparing two delivery modalities for PTH: insulin pump versus subcutaneous injections.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Serum Calcium in Children and Young Adults	Mean fasting serum calcium level at the end of week 13. After 13 weeks of PTH 1-34 administration, participants were admitted for five to seven days and fasting blood sample was collected each morning (6-8 am) for three days. Mean value for the three days was calculated.	Day 1-3 of inpatient evaluation at the conclusion of 13 weeks of PTH 1-34 delivered by pump or injection
Mean Serum Calcium in Adults	Mean fasting serum calcium level at the end of week 13. After 13 weeks of PTH 1-34 administration, participants were admitted for five to seven days and fasting blood sample was collected each morning (6-8 am) for three days. Mean value for the three days was calculated.	Day 1-3 of inpatient evaluation at the conclusion of 13 weeks of PTH 1-34 delivered by pump or injection
Mean Urine Calcium Excretion in Children and Young Adults	Mean 24-hour urine calcium excretion at the end of week 13. After 13 weeks of PTH 1-34 administration, participants were admitted for five to seven days and 24 hour urine sample was collected each day for three days. Mean value for the three days was calculated with values corrected for body surface area in children and young adults.	Day 1-3 of inpatient evaluation at the conclusion of 13 weeks of PTH 1-34 delivered by pump or injection
Mean Urine Calcium Excretion in Adults	Mean 24-hour urine calcium excretion at the end of week 13. After 13 weeks of PTH 1-34 administration, participants were admitted for five to seven days and 24 hour urine sample was collected each day for three days. Mean value for the three days was calculated.	Day 1-3 of inpatient evaluation at the conclusion of 13 weeks of PTH 1-34 delivered by pump or injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Serum Phosphorus in Children and Young Adults	Mean fasting serum phosphorus level at the end of week 13. After 13 weeks of PTH 1-34 administration, participants were admitted for five to seven days and fasting blood sample was collected each morning (6-8 am) for three days. Mean value for the three days was calculated.	Day 1-3 of inpatient evaluation at the conclusion of 13 weeks of PTH 1-34 delivered by pump or injection
Mean Serum Phosphorus in Adults	Mean fasting serum phosphorus level at the end of week 13. After 13 weeks of PTH 1-34 administration, participants were admitted for five to seven days and fasting blood sample was collected each morning (6-8 am) for three days. Mean value for the three days was calculated.	Day 1-3 of inpatient evaluation at the conclusion of 13 weeks of PTH 1-34 delivered by pump or injection
Mean Urine Phosphorus Excretion in Children and Young Adults	Mean 24-hour urine phosphorus excretion at the end of week 13. After 13 weeks of PTH 1-34 administration, participants were admitted for five to seven days and 24 hour urine sample was collected each day for three days. Mean value for the three days was calculated with values corrected for body surface area in children and young adults.	Day 1-3 of inpatient evaluation at the conclusion of 13 weeks of PTH 1-34 delivered by pump or injection
Mean Urine Phosphorus Excretion in Adults	Mean 24-hour urine phosphorus excretion at the end of week 13. After 13 weeks of PTH 1-34 administration, participants were admitted for five to seven days and 24 hour urine sample was collected each day for three days. Mean value for the three days was calculated.	Day 1-3 of inpatient evaluation at the conclusion of 13 weeks of PTH 1-34 delivered by pump or injection
Mean Serum Magnesium in Children and Young Adults	Mean fasting serum magnesium level at the end of week 13. After 13 weeks of PTH 1-34 administration, participants were admitted for five to seven days and fasting blood sample was collected each morning (6-8 am) for three days. Mean value for the three days was calculated.	Day 1-3 of inpatient evaluation at the conclusion of 13 weeks of PTH 1-34 delivered by pump or injection
Mean Serum Magnesium in Adults	Mean fasting serum magnesium level at the end of week 13. After 13 weeks of PTH 1-34 administration, participants were admitted for five to seven days and fasting blood sample was collected each morning (6-8 am) for three days. Mean value for the three days was calculated.	Day 1-3 of inpatient evaluation at the conclusion of 13 weeks of PTH 1-34 delivered by pump or injection
Mean Urine Magnesium Excretion in Children and Young Adults	Mean 24-hour urine magnesium excretion at the end of week 13. After 13 weeks of PTH 1-34 administration, participants were admitted for five to seven days and 24 hour urine sample was collected each day for three days. Mean value for the three days was calculated with values corrected for body surface area in children and young adults.	Day 1-3 of inpatient evaluation at the conclusion of 13 weeks of PTH 1-34 delivered by pump or injection
Mean Urine Magnesium Excretion in Adults	Mean 24-hour urine magnesium excretion at the end of week 13. After 13 weeks of PTH 1-34 administration, participants were admitted for five to seven days and 24 hour urine sample was collected each day for three days. Mean value for the three days was calculated.	Day 1-3 of inpatient evaluation at the conclusion of 13 weeks of PTH 1-34 delivered by pump or injection
Mean Serum Alkaline Phosphatase in Children and Young Adults	Mean fasting serum alkaline phosphatase level at the end of week 13. After 13 weeks of PTH 1-34 administration, participants were admitted for five to seven days and fasting blood sample was collected each morning (6-8 am) for three days. Mean value for the three days was calculated.	Day 1-3 of inpatient evaluation at the conclusion of 13 weeks of PTH 1-34 delivered by pump or injection
Mean Serum Alkaline Phosphatase in Adults	Mean fasting serum alkaline phosphatase level at the end of week 13. After 13 weeks of PTH 1-34 administration, participants were admitted for five to seven days and fasting blood sample was collected each morning (6-8 am) for three days. Mean value for the three days was calculated.	Day 1-3 of inpatient evaluation at the conclusion of 13 weeks of PTH 1-34 delivered by pump or injection
Mean Serum Bone-specific Alkaline Phosphatase in Children and Young Adults	Mean fasting serum bone-specific alkaline phosphatase level at the end of week 13. After 13 weeks of PTH 1-34 administration, participants were admitted for five to seven days and fasting blood sample was collected each morning (6-8 am) for three days. Mean value for the three days was calculated.	Day 1-3 of inpatient evaluation at the conclusion of 13 weeks of PTH 1-34 delivered by pump or injection
Mean Serum 1,25-hydroxyvitamin D3 in Children and Young Adults	Mean fasting serum 1,25-hydroxyvitamin D3 level at the end of week 13. After 13 weeks of PTH 1-34 administration, participants were admitted for five to seven days and fasting blood sample was collected each morning (6-8 am) for three days. Mean value for the three days was calculated.	Day 1-3 of inpatient evaluation at the conclusion of 13 weeks of PTH 1-34 delivered by pump or injection
Mean Serum 1,25-hydroxyvitamin D3 in Adults	Mean fasting serum 1,25-hydroxyvitamin D3 level at the end of week 13. After 13 weeks of PTH 1-34 administration, participants were admitted for five to seven days and fasting blood sample was collected each morning (6-8 am) for three days. Mean value for the three days was calculated.	Day 1-3 of inpatient evaluation at the conclusion of 13 weeks of PTH 1-34 delivered by pump or injection
Mean Serum 25-hydroxyvitamin D3 in Children and Young Adults	Mean fasting serum 25-hydroxyvitamin D3 level at the end of week 13. After 13 weeks of PTH 1-34 administration, participants were admitted for five to seven days and fasting blood sample was collected each morning (6-8 am) for three days. Mean value for the three days was calculated.	Day 1-3 of inpatient evaluation at the conclusion of 13 weeks of PTH 1-34 delivered by pump or injection
Mean Serum 25-hydroxyvitamin D3 in Adults	Mean fasting serum 25-hydroxyvitamin D3 level at the end of week 13. After 13 weeks of PTH 1-34 administration, participants were admitted for five to seven days and fasting blood sample was collected each morning (6-8 am) for three days. Mean value for the three days was calculated.	Day 1-3 of inpatient evaluation at the conclusion of 13 weeks of PTH 1-34 delivered by pump or injection
Mean Urine Creatinine Clearance Excretion in Children and Young Adults	Mean 24-hour urine creatinine clearance excretion at the end of week 13. After 13 weeks of PTH 1-34 administration, participants were admitted for five to seven days and 24 hour urine sample was collected each day for three days. Mean value for the three days was calculated with values corrected for body surface area in children and young adults.	Day 1-3 of inpatient evaluation at the conclusion of 13 weeks of PTH 1-34 delivered by pump or injection
Mean Urine Creatinine Clearance Excretion in Adults	Mean 24-hour urine creatinine clearance excretion at the end of week 13. After 13 weeks of PTH 1-34 administration, participants were admitted for five to seven days and 24 hour urine sample was collected each day for three days. Mean value for the three days was calculated.	Day 1-3 of inpatient evaluation at the conclusion of 13 weeks of PTH 1-34 delivered by pump or injection
Mean Serum Osteocalcin in Children and Young Adults	Mean fasting serum osteocalcin level at the end of week 13. After 13 weeks of PTH 1-34 administration, participants were admitted for five to seven days and fasting blood sample was collected each morning (6-8 am) for three days. Mean value for the three days was calculated.	Day 1-3 of inpatient evaluation at the conclusion of 13 weeks of PTH 1-34 delivered by pump or injection
Mean Serum Osteocalcin in Adults	Mean fasting serum osteocalcin level at the end of week 13. After 13 weeks of PTH 1-34 administration, participants were admitted for five to seven days and fasting blood sample was collected each morning (6-8 am) for three days. Mean value for the three days was calculated.	Day 1-3 of inpatient evaluation at the conclusion of 13 weeks of PTH 1-34 delivered by pump or injection
Mean Urine N-terminal Telopeptide Level in Children and Young Adults	Mean 24-hour urine N-terminal telopeptide of type 1 collagen excretion at the end of week 13. After 13 weeks of PTH 1-34 administration, participants were admitted for five to seven days and 24 hour urine sample was collected each day for three days. Mean value for the three days was calculated with values corrected for body surface area in children and young adults.	Day 1-3 of inpatient evaluation at the conclusion of 13 weeks of PTH 1-34 delivered by pump or injection
Mean Urine N-terminal Telopeptide Level in Adults	Mean 24-hour urine N-terminal telopeptide of type 1 collagen excretion at the end of week 13. After 13 weeks of PTH 1-34 administration, participants were admitted for five to seven days and 24 hour urine sample was collected each day for three days. Mean value for the three days was calculated.	Day 1-3 of inpatient evaluation at the conclusion of 13 weeks of PTH 1-34 delivered by pump or injection
Mean Blood Mineral Levels - Calcium, Phosphorus, Magnesium	Mean fasting serum calcium, phosphorus, and magnesium levels first three days of initial baseline inpatient admission. Participants were admitted for five to seven days and fasting blood sample was collected each morning (6-8 am) for three days. Mean value for the three days was calculated.	Day 1-3 of baseline initial inpatient evaluation
Mean Urine Mineral Excretion - Calcium, Phosphorus, Magnesium	Mean 24-hour urine calcium, phosphorus, and magnesium excretion first 3 days of initial baseline inpatient admission. Participants were admitted for five to seven days and 24 hour urine sample was collected each day for three days. Mean value for the three days was calculated with values corrected for body surface area in children and young adults.	Day 1-3 of baseline initial inpatient evaluation
Mean Serum Alkaline Phosphatase	Mean fasting serum alkaline phosphatase level first 3 days of initial baseline inpatient admission. Participants were admitted for five to seven days and fasting blood sample was collected each morning (6-8 am) for three days. Mean value for the three days was calculated.	Day 1-3 of baseline initial inpatient evaluation
Mean Serum Bone Specific Alkaline Phosphatase in Children and Young Adults	Mean fasting serum bone specific alkaline phosphatase level first 3 days of initial baseline inpatient admission. Participants were admitted for five to seven days and fasting blood sample was collected each morning (6-8 am) for three days. Mean value for the three days was calculated.	Day 1-3 of baseline initial inpatient evaluation
Mean Serum 1,25-hydroxyvitamin D3	Mean fasting serum 1,25-hydroxyvitamin D3 level first 3 days of initial baseline inpatient admission. Participants were admitted for five to seven days and fasting blood sample was collected each morning (6-8 am) for three days. Mean value for the three days was calculated.	Day 1-3 of baseline initial inpatient evaluation
Mean Serum Bone Minerals - 25-hydroxyvitamin D3 and Osteocalcin	Mean fasting serum 25-hydroxyvitamin D3 and osteocalcin levels first 3 days of initial baseline inpatient admission. Participants were admitted for five to seven days and fasting blood sample was collected each morning (6-8 am) for three days. Mean value for the three days was calculated.	Day 1-3 of baseline initial inpatient evaluation
Mean Urine Creatinine Clearance Excretion	Mean 24-hour urine creatinine clearance excretion first 3 days of initial baseline inpatient admission. Participants were admitted for five to seven days and 24 hour urine sample was collected each day for three days. Mean value for the three days was calculated with values corrected for body surface area in children.	Day 1-3 of baseline initial inpatient evaluation
Mean Urine N-terminal Telopeptide Level	Mean 24-hour urine N-terminal telopeptide of type 1 collagen excretion first 3 days of initial baseline inpatient admission. Participants were admitted for five to seven days and 24 hour urine sample was collected each day for three days. Mean value for the three days was calculated with values corrected for body surface area in children.	Day 1-3 of baseline initial inpatient evaluation

Collaborators and Investigators

• Sponsor: National Institutes of Health Clinical Center (CC)
• 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)

Publications and helpful links

General Publications

• Winer KK, Fulton KA, Albert PS, Cutler GB Jr. Effects of pump versus twice-daily injection delivery of synthetic parathyroid hormone 1-34 in children with severe congenital hypoparathyroidism. J Pediatr. 2014 Sep;165(3):556-63.e1. doi: 10.1016/j.jpeds.2014.04.060. Epub 2014 Jun 16.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 22, 2008
• Primary Completion (Actual): April 7, 2014
• Study Completion (Actual): April 7, 2014

Study Registration Dates

• First Submitted: August 28, 2008
• First Submitted That Met QC Criteria: August 28, 2008
• First Posted (Estimated): August 29, 2008

Study Record Updates

• Last Update Posted (Actual): March 4, 2026
• Last Update Submitted That Met QC Criteria: February 17, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Hypocalcemia; Hypoparathyroidism; Parathyroid Hormone 1-34; APECED; CASR
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Autoimmune Diseases; Immune System Diseases; Water-Electrolyte Imbalance; Parathyroid Diseases; Calcium Metabolism Disorders; Nutritional and Metabolic Diseases; Hypoparathyroidism; Hypocalcemia; Polyendocrinopathies, Autoimmune; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormones; Parathyroid Hormone
• Other Study ID Numbers: 080203; 08-CH-0203

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No