Contribution of Bone to Urine Citrate
试验速览
- 阶段
- 不适用
- 状态
- Enrolling By Invitation
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Correlation of change in Urine Citrate levels to change in Potassium levels with change in bone turnover markers at 1 month after initiating treatment
研究概览
简要总结
Identification of the mechanisms by which bone contributes to urine citrate could lead to alternative explanations for and approaches to hypocitraturia. This proposal to explore the role of bone in urine citrate addresses the mission of the CMMCR to discover new mechanisms and innovative therapies for diseases of mineral metabolism. The results will be used to apply for extramural funding to further examine the nonrenal regulation of UCit.
Hypothesis: Serum citrate is a function of bone citrate formation dependent on both bone mass and bone turnover. 20 subjects with osteoporosis naïve to treatment will be identified to examine bone parameters that correlate with ΔUcit/Δk.
Use of potent anti-osteoporotic therapies to increase the likelihood of identifying significant bone turnover and BMD correlations with ΔUcit/Uk will take place in this study.
Plan to achieve the following aim:
- Correlate ∆ Ucit/∆k in response to acute KCit load with:
- Bone turnover marker at baseline
- BMD at baseline
- Change in bone turnover markers at 1 month and 6 months with each osteoporosis treatment modality (anti-resorptive agents such as Zoledronic acid or Denosumab, or the Anabolic agent Romosozumab)
- Change in bone mineral density at 6 with each osteoporosis treatment modality (anti-resorptive agents such as Zoledronic acid or Denosumab, or the Anabolic agent Romosozumab)
详细描述
Screening Visit: Before enrollment into the trial, potential candidates will undergo screening, whereby the study team will conduct a physical exam and ask questions about the subject's medical history, including medications and any surgical procedures. Those who meet the entry-exclusion criteria will be selected for consideration into the study. During screening, subjects will provide information on or have the following exams, tests or procedures:
- Social and medical history;
- Medications;
- Vital signs;
- Demographic information (age, gender, ethnic origin);
- Personal information (name, date of birth, address, telephone number, emergency contact, and referring physician)
Assignment to groups:
Group 1- Patients with osteoporosis naïve to treatment will initiate treatment with anti-resorptive agents (zoledronic acid or denosumab).
Group 2- - Patients with osteoporosis naïve to treatment will initiate treatment with anabolic agents (romosozumab).
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Osteoporosis naïve to treatment
排除标准
- •eGFR < 60 ml/min
- •chronic diarrhea or gastrointestinal illness
研究组 & 干预措施
Anti-resorptive agents use Group
Patients with osteoporosis naïve to treatment will initiate treatment with anti-resorptive agents (zoledronic acid or denosumab)
干预措施: KCit Load (40 meq) (Other)
Anabolic agents use Group
Patients with osteoporosis naïve to treatment will initiate treatment with anabolic agents (romosozumab)
干预措施: KCit Load (40 meq) (Other)
Anti-resorptive agents use Group
Patients with osteoporosis naïve to treatment will initiate treatment with anti-resorptive agents (zoledronic acid or denosumab)
干预措施: Anti-resorptive agents (Drug)
Anti-resorptive agents use Group
Patients with osteoporosis naïve to treatment will initiate treatment with anti-resorptive agents (zoledronic acid or denosumab)
干预措施: Metabolic / prescribed diet (Other)
Anabolic agents use Group
Patients with osteoporosis naïve to treatment will initiate treatment with anabolic agents (romosozumab)
干预措施: Metabolic / prescribed diet (Other)
Anabolic agents use Group
Patients with osteoporosis naïve to treatment will initiate treatment with anabolic agents (romosozumab)
干预措施: Anabolic Agents (Drug)
结局指标
主要结局
Correlation of change in Urine Citrate levels to change in Potassium levels with change in bone turnover markers at 1 month after initiating treatment
时间窗: Baseline, 1month after initiating treatment
Change in Urine Citrate levels to change in Potassium levels from the 24h urine samples is measured and will be correlated with baseline and post treatment bone turnover markers by multiple linear regression modeling using forward and backward selection.
Correlation of change in Urine Citrate levels to change in Potassium levels with change in bone turnover markers at 6 months after initiating treatment
时间窗: Baseline, 6 months after initiating treatment
Change in Urine Citrate levels to change in Potassium levels from the 24h urine samples is measured and will be correlated with baseline and post treatment bone turnover markers by multiple linear regression modeling using forward and backward selection.
Correlation of change in Urine Citrate levels to change in Potassium levels with bone densitometry at baseline
时间窗: Baseline
Change in Urine Citrate levels to change in Potassium levels will be correlated with bone densitometry at lumbar spine, right hip, and radius
Correlation of change in Urine Citrate levels to change in Potassium levels with change in bone densitometry at 6 months after initiating treatment
时间窗: Baseline, 6 months after initiating treatment
Change in Urine Citrate levels to change in Potassium levels will be correlated with change in bone densitometry at lumbar spine, right hip, and radius
K Cit load
时间窗: Predose, 0.5, 1, 2, 3, 4 hours after drug administration in Phases 1, 2, 3
The AUC for citrate will be calculated from the serum and urine levels based on the assumption that oral K Cit is 100% absorbed to estimate hepatic uptake effect on filtered load. The fractional excretion of citrate (FeCit) will be calculated from hourly serum and urine creatinine and citrate levels (FeCit = (serum Cit x Urine Cr)/urine Cit x serum Cr) x 100. Differences in FeCit will be correlated with ΔUcit/Δk and will be used to discriminate changes in ΔUcit/Δk due to filtered load vs renal handling.
次要结局
未报告次要终点
研究者
Eleanor Lederer
Professor
University of Texas Southwestern Medical Center