Pharmacogenomics to Predict Responses to SGLT2 Inhibitors
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 700
- 主要终点
- Urinary glucose excretion (during the time interval 24-48 hours after first administration of canagliflozin)
研究概览
简要总结
Five daily doses of canagliflozin (300 mg) will be administered to healthy volunteers. Pharmacodynamic responses to canagliflozin will be assessed both at 2 days and 6 days after administration of the first dose of canagliflozin. A genome-wide association study (GWAS) will be conducted to search for genetic variants that are associated with each of the pharmacodynamic responses to canagliflozin.
详细描述
After obtaining informed consent, healthy Amish research subjects will be screened for eligibility. Immediately after obtaining blood samples for baseline clinical chemistry tests wills, patients will initiate 5 days of canagliflozin (300 mg) treatment. Fasting blood samples will be obtained to assess pharmacodynamic responses at both 48 hours and 120 hours after initiating canagliflozin. The principal pharmacodynamic responses will include 24 hour urinary excretion of glucose, serum chemistries (phosphorus, FGF23, 1,25-dihydroxyvitamin D, parathyroid hormone (PTH), glucagon, beta-hydroxybutyrate, acetoacetate, procollagen type I N-terminal peptide (P1NP), and beta-CTX). Research subjects will undergo genotyping, and a genome-wide association study will be conducted to search for genetic variants that are associated with pharmacodynamic responses to canagliflozin.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Of Amish descent
- •Age 18 or older
- •BMI: 18-40 kg/m2
排除标准
- •Known allergy to canagliflozin
- •History of diabetes, random glucose greater than 200 mg/dL, or HbA1c greater than or equal to 6.5%
- •Currently taking diuretics, antihypertensive medication uric acid lowering medications, or other medication that the investigator judges will make interpretation of the results difficult
- •Significant debilitating chronic cardiac, hepatic, pulmonary, or renal disease or other diseases that the investigator judges will make interpretation of the results difficult or increase the risk of participation
- •Seizure disorder
- •Unwilling to go off of vitamin supplements and over the counter medication (except for acetaminophen) for at least two weeks prior to the first home visit and agree to avoid these medications for the duration of the study.
- •Positive urine human chorionic gonadotropin test or known pregnancy within 3 months of the start of the study
- •Estimated glomerular filtration rate less than 60 mL/min
- •Currently breast feeding or breast feeding within 3 month of the start of the study
- •Liver function tests greater than 2 times the upper limit of normal
- •Hematocrit less than 35%
- •Abnormal thyroid hormone stimulating hormone
研究组 & 干预措施
Single arm
Healthy volunteers will receive canagliflozin to assess pharmacodynamic responses to drug.
干预措施: Canagliflozin (Drug)
结局指标
主要结局
Urinary glucose excretion (during the time interval 24-48 hours after first administration of canagliflozin)
时间窗: 24-48 hours
Urine collection will be initiated 24 hours after initiation of canagliflozin treatment, and continued for an additional 24 hours.
次要结局
- Bone-related biomarkers(120 hrs)
- Ketosis-related biomarkers(120 hurs)
- Serum uric acid(120 hrs)
研究者
Simeon I. Taylor
Professor of Medicine
University of Maryland, Baltimore