Evaluation of Factors That Affect Skeletal Responses to PTH
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Changes in Indices of Bone Turnover
研究概览
简要总结
Parathyroid hormone (PTH) increases bone formation and thereby improves bone density and bone strength in postmenopausal women with osteoporosis. However, prolonged PTH treatment increases bone formation less and less over time. This study will test whether increasing the daily dose of PTH sustains its ability to improve bone formation, and optional sub-studies will test several potential reasons why PTH's effects on bone formation decline over time.
详细描述
In women with postmenopausal osteoporosis, PTH increases bone mineral density more than anti-resorptive agents, and its use markedly reduces the incidence of new spine and non-spine fractures. Still, PTH is not a cure for osteoporosis in many patients because PTH-stimulated bone formation declines as PTH therapy continues. Biochemical analyses suggest that bone formation and resorption peak after 6 to 9 months of daily PTH therapy and then decline progressively.
The study will last 18 months. Blood, urine, and bone density tests will occur at screening. At the start of the study, participants will be randomly assigned to one of two PTH dose regimens. Patients will go to Massachusetts General Hospital at Months 0, 3, 6, 9, 12, 15, and 18 for blood and urine collection. In addition, bone density tests by DXA will be performed at Months 0, 6, 12, and 18, and by quantitative CT scans at Months 0 and 18. Approximately 6 weeks after any change in PTH dose, each participant's blood calcium will be checked 4 to 6 hours after that day's PTH injection, and her 24-hour urine calcium excretion will also be checked.
Participants may enroll in optional substudies that will test whether reduced skeletal responses to long-term treatment with PTH are accompanied by changes in its absorption and/or destruction and whether reduced skeletal responses to long-term treatment with PTH are accompanied by parallel reductions in kidney responses to PTH.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 46 Years 至 85 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Three or more years after menopause
- •Bone mineral density T-score < or = -2.0 by dual-energy x-ray absorptiometry (DXA) of vertebrae or femoral neck, or by quantitative computerized tomography (QCT) of vertebral body trabeculae
排除标准
- •Cannot walk without assistance
- •Significant heart, kidney, liver, or malignant disease
- •Current alcohol abuse
- •Major psychiatric disorders
- •Other current or past disorders known to affect bone
- •Use of medications known to affect bone for > 7 days in the past 12 months
- •Use of bisphosphonates or fluoride
- •Abnormal blood calcium, PTH, 25-hydroxy vitamin D, creatinine, liver function tests, or complete blood count
- •Elevated calcium levels in 24-hour urine collection
研究组 & 干预措施
constant dose
Participants will receive synthetic human parathyroid hormone fragment 1-34 (hPTH 1-34) once-daily in a constant dose of 30 mcg/day.
干预措施: synthetic hPTH 1-34 (Drug)
ascending dose
Participants will receive synthetic human parathyroid hormone fragment 1-34 (hPTH 1-34) once-daily in a dose that ascends at 6 month intervals (20-30-40 mcg/day).
干预措施: synthetic hPTH 1-34 (Drug)
结局指标
主要结局
Changes in Indices of Bone Turnover
时间窗: Each index of bone turnover was measured at study month 0, 1.5, 3, 6, 7.5, 9, 12, 13.5, 15, and 18.
Change from month 0 (pre-treatment) baseline serum aminoterminal propeptide of type I collagen (PINP), osteocalcin (OC), and C-terminal telopeptide (CTX), expressed as an area under the curve (AUC). Each marker measurement result was multiplied by the corresponding subject-specific elapsed study time interval using the trapezoidal rule, and these products were summed to generate a subject-specific AUC (months\*ng/ml) for the marker.
次要结局
- Change in Bone Mineral Density (BMD)(baseline and 18 months (12 months in 4 subjects))
研究者
Robert M. Neer, MD
Associate Professor of Medicine
Massachusetts General Hospital