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

NCT00743782 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 08020308-CH-0203
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hypoparathyroidism; Hypocalcemia; Autoimmune Polyendocrine Syndrome Type 1; Autosomal Dominant Hypocalcemia Type 1 (ADH1)

Keywords

Parathyroid Hormone 1-34; Hypoparathyroidism; Hypocalcemia; APECED; CASR

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (29)

• Mean Serum Phosphorus 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 Serum Phosphorus in 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 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

  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

  Day 1-3 of inpatient evaluation at the conclusion of 13 weeks of PTH 1-34 delivered by pump or injection

Study Arms (2)

PTH 1-34 delivered through pump, then subcutaneous injection

ACTIVE COMPARATOR

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

PTH 1-34 subcutaneous injection, then delivered through pump

ACTIVE COMPARATOR

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

Interventions

Synthetic Human Parathyroid Hormone 1-34 pump DRUG

comparing two delivery modalities for PTH: insulin pump versus subcutaneous injections.

PTH 1-34 delivered through pump, then subcutaneous injection; PTH 1-34 subcutaneous injection, then delivered through pump

Eligibility Criteria

• Age: 7 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institutes of Health Clinical Center (CC): lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (2)

• 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.

  PMID: 24948345 RESULT

• 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.

  PMID: 22090268 RESULT

MeSH Terms

Conditions

Hypoparathyroidism; Hypocalcemia; Polyendocrinopathies, Autoimmune

Condition Hierarchy (Ancestors)

Parathyroid Diseases; Endocrine System Diseases; Calcium Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Water-Electrolyte Imbalance; Autoimmune Diseases; Immune System Diseases

Limitations and Caveats

Limitations include small sample size.

Results Point of Contact

• Title: Dr. Karen Winer, MD
• Organization: National Institute of Child Health and Human Development

winerk@mail.nih.gov

+1 301 435 6877

Study Officials

• Karen K Winer, M.D.

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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Model Details: Randomized crossover design; all patients are their own controls. Comparing delivery of PTH 1-34 through an insulin pump (Omnipod) vs. PTH 1-34 by twice-daily subcutaneous injections.

Study Record Dates

• First Submitted: August 28, 2008
• First Posted: August 29, 2008
• Study Start: August 22, 2008
• Primary Completion: April 7, 2014
• Study Completion: April 7, 2014
• Last Updated: March 4, 2026
• Results First Posted: March 4, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)