Randomized, Double-blind, Placebo-controlled, Phase 1A Clinical Trial to Assess the Safety, Pharmacokinetic and Pharmacodynamic Effects of Single Escalating Doses of a Standardized Epimedium Prenylflavonoids (EP) Extract (HSA Chinese Proprietary Medicine No: 123317) in Healthy Men.
试验速览
- 阶段
- 1 期
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Incidence and severity of adverse events/serious adverse events
研究概览
简要总结
The primary objective of the trial is to develop Epimedium Prenylflavonoid (EP) extract as a pharmaceutical-quality intervention for post-menopausal osteoporosis and cardiovascular disease. There will be 3 cohorts of 10 healthy men each for the Phase 1 study. In each cohort, 8 men will receive the Epimedium capsules and 2 men will received the matched controls.
详细描述
Prenylflavonoids and its glycoside derivatives isolated from the Traditional Chinese Medicine (TCM), Epimedium, have potent estrogenic properties. The principal bioactive compounds in Epimedium are the prenylflavonoids, icaritin, and their glycosylated derivatives which can enhance osteoblastic differentiation and mineralization, inhibits bone resorption, and induces apoptosis of osteoclasts. Animal experiments indicate that icariin can prevent bone loss induced by ovariectomized (OVX) in rats, through its stimulatory effects on osteoblast growth and function, and inhibitory action on osteoclast cells.
Epimedium has also demonstrated significant cardiovascular benefits with positive actions on vascular reactivity, endothelial function and thrombosis in human subjects. Notably, icariin, demonstrated a significant nitric oxide (NO)-dependent vasorelaxation of precontracted coronary arterial rings with intact endothelium in a concentration-dependent manner, via the activation of endothelial nitric oxide synthase protein and NO-cyclic guanidine monophosphate (cGMP) pathway. Epimedium prenylflavonoids (EP) can prevent steroid-associated osteonecrosis in rabbit model and notably, reduce thrombosis incidence and shrink fat-cell-size significantly. This striking combination of properties highlights the immense potential in EP for osteoporosis and cardiovascular health.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 21 Years 至 45 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Healthy men.
排除标准
- •Hepatitis B patients
研究组 & 干预措施
Epimedium Prenylflavonoids Extract
Single oral doses of EP (370 mg, 740 mg and 1110 mg) capsules would be orally administered.
干预措施: Epimedium Prenylflavonoids Extract (Drug)
Placebo
Single oral doses of Placebo (370 mg, 740 mg and 1110 mg) capsules would be orally administered.
干预措施: Placebo (Drug)
结局指标
主要结局
Incidence and severity of adverse events/serious adverse events
时间窗: 8 to10 days
Incidence and severity of adverse events/serious adverse events based on history, physical examination and vital signs, hematology and clinical chemistry.
次要结局
- Estrogenic biomarkers(1 to 2 months)
- interleukin-6 (IL-6)(1 month)
- high-sensitivity C-reactive protein (hs-CRP)(1 month)
- F2-isoprostanes(1 month)
- Demethylicaritin (DICT)(3 months)
- lcariin(3 months)
- Ex vivo osteoblast and osteoclast activities(6 to 9 months)
- multiple platelet aggregation(1 month)
- Icaritin (ICT)(3 months)
- icariside 1(3 months)
- icariside II(3 months)
研究者
Obstetrics & Gynaecology
Professor
National University Hospital, Singapore