Determining the Maximal Safe Dose of a Continuous Infusion of Parathyroid Hormone-related Protein(1-36): Effects on Bone Formation
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 14
- 试验地点
- 1
- 主要终点
- Dose Limiting Toxicity (DLT)
研究概览
简要总结
This is a dose escalation study to determine the maximum tolerable dose of Parathyroid Hormone-related Protein, PTHrP, that can be given safely over one week. The investigators plan to infuse low doses of intravenous PTHrP to determine if it leads to a sustained and progressive suppression of bone formation as occurs in humoral hypercalcemia of malignancy (HHM) or an increase in bone formation as occurs in hyperparathyroidism (HPT). Additionally, the investigators will assess the direct influence of PTHrp on markers of bone turnover, and plasma 1,25 (OH)2 vitamin D regulation in healthy human volunteers.
详细描述
During this research the investigators administer PTHrP to healthy young volunteers in a controlled, continuous intravenous manner. As research subjects complete the week-long study without adverse effects, the dose of PThrP will be increased in later subjects. In the event of a significant adverse effect, immediate action will be taken to reverse it. The investigators want to estimate the effect of a sustainable level of mild hypercalcemia achieved by a week-long intravenous infusion of PTHrP has on vitamin D metabolism, markers of bone turnover and fractional excretion of calcium.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 24 Years 至 35 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy caucasian subjects of both sexes between the ages of 24-35 years, who are able to spend one week on the Clinical & Translational Research Center at the University of Pittsburgh Medical Center (UPMC) Montefiore
排除标准
- •Pregnancy
- •Any cardiac, renal, pulmonary, endocrine, musculoskeletal, hepatic, hematological, malignant or rheumatologic diseases
- •Body mass index great than 30
- •Significant alcohol or drug abuse
- •Baseline hypotension or hypertension
- •Abnormal screening labs
- •Use of certain chronic medications excluding oral contraceptives
- •Receiving an investigational drug in the last 90 days
- •Previously receiving PTH or PTHrP
- •African-American race
研究组 & 干预措施
PTHrP(1-36) 2 pmol/kg/hr
PTHrP(1-36) at 2 picomoles/kg/hr for one week.
干预措施: PTHrP (1-36) (Drug)
PTHrP (1-36) 4 pmol/kg/hr
PTHrP(1-36) at 4 picomoles/kg/hr for one week.
干预措施: PTHrP (1-36) (Drug)
PTHrP(1-36) 5 pmol/kg/hr
PTHrP(1-36) at 5 picomoles/kg/hr for one week.
干预措施: PTHrP (1-36) (Drug)
PTHrP(1-36) 6 pmol/kg/hr
PTHrP(1-36) at 6 picomoles/kg/hr for one week.
干预措施: PTHrP (1-36) (Drug)
结局指标
主要结局
Dose Limiting Toxicity (DLT)
时间窗: 12 hours after the infusion was started then q 8 hours for 7 days
DLT was defined as achieving one major criterion or two minor criteria rated at ≥ 2 on a scale of 0-5. The major criteria were defined as symptomatic orthostatic hypotension (systolic BP fall \>30 mm/hg), tachycardia (pulse \> 120), hypertension (systolic BP \>160 mm/hg on 2 occasions), hypercalcemia (serum calcium ≥ 12 mg/dl), and hypophosphatemia (serum phosphorous \< 1.5 mg/dl). Minor criteria included symptoms such as flushing, nausea, abdominal or muscle cramps, dizziness, lightheadedness, palpitations, etc.
Total Serum Calcium
时间窗: 12 hours after the infusion was started then q 8 hours for 7 days, Follow-up 1 week after infusion complete
mg/dl
Ionized Serum Calcium
时间窗: 12 hours after the infusion was started then q 8 hours for 7 days, Follow-up 1 week after infusion complete
mg/dl
Serum Phosphorous
时间窗: 12 hours after the infusion was started then q 8 hours for 7 days, Follow-up 1 week after infusion complete
mg/dl
次要结局
- 1,25 Vitamin D(Baseline and Daily through day 8 then at follow-up visit)
- 24 Hour Urine Calcium(24 hours)
- Tubular Maximum of Phosphorous (TmP/GFR)(daily)
- Serum Amino-terminal Telopeptide of Collagen -1 (sNTX)(Baseline, Daily, and 1 week follow-up)
- Serum Carboxy-terminal Telopeptide of Collagen -1 (sCTX)(Baseline, Daily, and 1 week follow-up)
- Amino-terminal Peptides of Procollagen 1 (P1NP)(Baseline, Daily, and 1 week follow-up)
- Bone Specific Alkaline Phosphatase (BSAP)(Baseline, Daily, and 1 week follow-up)
- Parathyroid Hormone (1-84)(Baseline and Daily)
- Fractional Excretion of Calcium(daily)
研究者
Mara Horwitz
Associate Professor of Medicne
University of Pittsburgh