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

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.