Trial of Indole-3-Carbinol & Silibinin
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 21
- 试验地点
- 1
- 主要终点
- Safety of the combination of I3C + Sil
研究概览
简要总结
This is a non-therapeutic, Phase 1 clinical trial to examine the safety, pharmacokinetic (PK) characteristics, and pharmacodynamics (PD) effect of indole-3-carbinol (I3C) and silibinin (Sil) in healthy subjects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 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
- •Adult ≥ 18 years old
- •Current smoker of ≥ 8 cigarettes per day for at least the last 6 months by self-report
- •Adequate blood counts, and adequate liver and kidney function defined as follows:
- •Hemoglobin ≥ 9 g/dL for women, ≥ 10 g/dL for men
- •Platelet count ≥ 100 x 10^9/L
- •Total bilirubin ≤ Institutional upper limit of normal (≤ 1.3 mg/dL for UMMC)
- •ALT ≤ 1.5 times institutional upper limit of normal
- •Creatinine ≤ 1.4 g/dL and estimated GFR ≥ 80 mL/min/1.7m2
- •Able to understand the experimental nature of the study and provide informed written consent
排除标准
- •Chronic proton pump inhibitor, H2-blocker (i.e., ranitidine, famotidine), and/or calcium carbonate use
- •History of gastric bypass surgery, gastric banding, bowel resection, malabsorption syndromes such as celiac sprue or pancreatic insufficiency, or other conditions that may affect gastric or intestinal absorption of nutrients
- •Current use of tobacco products other than cigarettes (i.e. snuff, snuz, smokeless tobacco, cigars, pipes), or use of these products within 3 months of study registration
- •Major or chronic medical disease, including heart disease, poorly controlled diabetes, etc., to be adjudicated by the principal investigator
- •Known active malignancy
- •History of aerodigestive malignancies
- •Women who are pregnant, intend to become pregnant within 3 months of study registration, or who are lactating. Women of childbearing potential must have a negative urine pregnancy test within 14 days of starting the assigned intervention
- •Antibiotic use within 2 months of study registration by self-report
- •History of respiratory tract cancer
- •Known allergy to I3C, Sil, or its components
- •Psychiatric and/or social situations that would potentially limit compliance with study requirements
研究组 & 干预措施
Single-dose PK study
Subjects will take the assigned dose of I3C, Sil, or I3C + Sil once at the study center. Ten mL of blood will be collected at the time points described in Section 9.14. Concurrently, urine will also be collected for 24 hours after the first dose of I3C, Sil or I3C + Sil, divided into the time intervals.
干预措施: Indole-3-Carbinol (Drug)
Single-dose PK study
Subjects will take the assigned dose of I3C, Sil, or I3C + Sil once at the study center. Ten mL of blood will be collected at the time points described in Section 9.14. Concurrently, urine will also be collected for 24 hours after the first dose of I3C, Sil or I3C + Sil, divided into the time intervals.
干预措施: Silibinin (Drug)
Single-dose PK study
Subjects will take the assigned dose of I3C, Sil, or I3C + Sil once at the study center. Ten mL of blood will be collected at the time points described in Section 9.14. Concurrently, urine will also be collected for 24 hours after the first dose of I3C, Sil or I3C + Sil, divided into the time intervals.
干预措施: Silibin (Drug)
Multi-dose PK Study
Subjects will take the assigned dose of I3C, Sil, or I3C + Sil for 8 weeks. Ten mL of blood will be collected at the time points described in Section 9.14. Concurrently, urine will be collected for 24 hours after the first dose of I3C, Sil or I3C + Sil, divided into the time intervals.
干预措施: Indole-3-Carbinol (Drug)
Multi-dose PK Study
Subjects will take the assigned dose of I3C, Sil, or I3C + Sil for 8 weeks. Ten mL of blood will be collected at the time points described in Section 9.14. Concurrently, urine will be collected for 24 hours after the first dose of I3C, Sil or I3C + Sil, divided into the time intervals.
干预措施: Silibinin (Drug)
Multi-dose PK Study
Subjects will take the assigned dose of I3C, Sil, or I3C + Sil for 8 weeks. Ten mL of blood will be collected at the time points described in Section 9.14. Concurrently, urine will be collected for 24 hours after the first dose of I3C, Sil or I3C + Sil, divided into the time intervals.
干预措施: Silibin (Drug)
Safety Study
Safety data will be generated during the multi-dose PK and PD study, as DLT is not anticipated in the single-dose PK study. Enrollment into dose cohorts 1 and 2 can occur on a continuous basis. Enrollment for dose cohorts 3 and 4 will be done sequentially using a modified 3+3 design (see Section 8.2). The first three subjects enrolled into a dose cohort must complete at least 21 days of the multi-dose PK/PD study without a DLT before the remaining 4 subjects in the cohort can be enrolled.
干预措施: Indole-3-Carbinol (Drug)
Safety Study
Safety data will be generated during the multi-dose PK and PD study, as DLT is not anticipated in the single-dose PK study. Enrollment into dose cohorts 1 and 2 can occur on a continuous basis. Enrollment for dose cohorts 3 and 4 will be done sequentially using a modified 3+3 design (see Section 8.2). The first three subjects enrolled into a dose cohort must complete at least 21 days of the multi-dose PK/PD study without a DLT before the remaining 4 subjects in the cohort can be enrolled.
干预措施: Silibinin (Drug)
Safety Study
Safety data will be generated during the multi-dose PK and PD study, as DLT is not anticipated in the single-dose PK study. Enrollment into dose cohorts 1 and 2 can occur on a continuous basis. Enrollment for dose cohorts 3 and 4 will be done sequentially using a modified 3+3 design (see Section 8.2). The first three subjects enrolled into a dose cohort must complete at least 21 days of the multi-dose PK/PD study without a DLT before the remaining 4 subjects in the cohort can be enrolled.
干预措施: Silibin (Drug)
Cohort 4 PD Study
The effect of I3C, Sil, or I3C + Sil on the pharmacodynamic endpoints listed under the Secondary Objectives in Section 1.2 will be characterized. This PD study will be done concurrently with the multi-dose PK study. Subjects will take the assigned dose of I3C, Sil, or I3C + Sil for 8 weeks. Nasal epithelium, oral cavity cells, buccal cells, blood, and urine will be collected at the time points described in the study calendar in Section 4.0.
干预措施: Indole-3-Carbinol (Drug)
Cohort 4 PD Study
The effect of I3C, Sil, or I3C + Sil on the pharmacodynamic endpoints listed under the Secondary Objectives in Section 1.2 will be characterized. This PD study will be done concurrently with the multi-dose PK study. Subjects will take the assigned dose of I3C, Sil, or I3C + Sil for 8 weeks. Nasal epithelium, oral cavity cells, buccal cells, blood, and urine will be collected at the time points described in the study calendar in Section 4.0.
干预措施: Silibinin (Drug)
Cohort 4 PD Study
The effect of I3C, Sil, or I3C + Sil on the pharmacodynamic endpoints listed under the Secondary Objectives in Section 1.2 will be characterized. This PD study will be done concurrently with the multi-dose PK study. Subjects will take the assigned dose of I3C, Sil, or I3C + Sil for 8 weeks. Nasal epithelium, oral cavity cells, buccal cells, blood, and urine will be collected at the time points described in the study calendar in Section 4.0.
干预措施: Silibin (Drug)
结局指标
主要结局
Safety of the combination of I3C + Sil
时间窗: Week 8
Incidence of Dose Limiting Toxicities (DLTs)
Pharmacokinetic profile of I3C + Sil
时间窗: Week 8
Accumulation
次要结局
- Effect of I3C, Sil, or I3C + Sil on RNA sequencing from PBMC(Week 8)
- Effect of I3C, Sil, or I3C + Sil on circulating inflammatory markers(Week 8)
- Effect of I3C, Sil, or I3C + Sil on protein expression of phosphorylated-Akt (pAkt), pERK, pSTAT3 and NF-kB from peripheral blood mononuclear cells (PBMC)(Week 8)
- Effect of I3C, Sil, or I3C + Sil on waist circumference(Week 8)
- Effect of I3C, Sil, or I3C + Sil on circulating immunophenotype(Week 8)
- Effect of I3C, Sil, or I3C + Sil on fasting glucose(Week 8)
- Effect of I3C, Sil, or I3C + Sil on fasting insulin(Week 8)
- Effect of I3C, Sil, or I3C + Sil on lipid profile(Week 8)
- Effect of I3C, Sil, or I3C + Sil on leptin(Week 8)
- Effect of I3C, Sil, or I3C + Sil on body weight(Week 8)
- Effect of I3C, Sil, or I3C + Sil on PIK3CA pathway signaling in buccal cells(Week 8)
- Effect of I3C, Sil, or I3C + Sil on PIK3CA pathway signaling in oral cavity cells(Week 8)
- Effect of I3C, Sil, or I3C + Sil on PIK3CA pathway signaling in nasal mucosa(Week 8)