Comparing Pump vs. Subcutaneous Injection Delivery of PTH 1-34 in the Management of Chronic Hypoparathyroidism
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 21
- 试验地点
- 1
- 主要终点
- Mean Serum Calcium in Children and Young Adults
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 7 Years 至 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Synthetic Human Parathyroid Hormone 1-34 pump (Drug)
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.
干预措施: Synthetic Human Parathyroid Hormone 1-34 pump (Drug)
结局指标
主要结局
Mean Serum Calcium in Children and Young Adults
时间窗: Day 1-3 of inpatient evaluation at the conclusion of 13 weeks of PTH 1-34 delivered by pump or injection
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.
Mean Serum Calcium in Adults
时间窗: Day 1-3 of inpatient evaluation at the conclusion of 13 weeks of PTH 1-34 delivered by pump or injection
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.
Mean Urine Calcium Excretion in Children and Young Adults
时间窗: Day 1-3 of inpatient evaluation at the conclusion of 13 weeks of PTH 1-34 delivered by pump or injection
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.
Mean Urine Calcium Excretion in Adults
时间窗: Day 1-3 of inpatient evaluation at the conclusion of 13 weeks of PTH 1-34 delivered by pump or injection
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.
次要结局
- 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)
- Mean Serum Magnesium 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 Magnesium 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 Magnesium 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 Alkaline Phosphatase 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 Alkaline Phosphatase 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 Bone-specific Alkaline Phosphatase 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 1,25-hydroxyvitamin D3 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 1,25-hydroxyvitamin D3 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 25-hydroxyvitamin D3 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 25-hydroxyvitamin D3 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 Creatinine Clearance 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 Creatinine Clearance 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 Osteocalcin 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 Osteocalcin 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 N-terminal Telopeptide Level 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(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(Day 1-3 of baseline initial inpatient evaluation)
- Mean Urine Mineral Excretion - Calcium, Phosphorus, Magnesium(Day 1-3 of baseline initial inpatient evaluation)
- Mean Serum Alkaline Phosphatase(Day 1-3 of baseline initial inpatient evaluation)
- Mean Serum Bone Specific Alkaline Phosphatase in Children and Young Adults(Day 1-3 of baseline initial inpatient evaluation)
- Mean Serum 1,25-hydroxyvitamin D3(Day 1-3 of baseline initial inpatient evaluation)
- Mean Serum Bone Minerals - 25-hydroxyvitamin D3 and Osteocalcin(Day 1-3 of baseline initial inpatient evaluation)
- Mean Urine Creatinine Clearance Excretion(Day 1-3 of baseline initial inpatient evaluation)
- Mean Urine N-terminal Telopeptide Level(Day 1-3 of baseline initial inpatient evaluation)