Clinical trial NCT02931305: Epimedium Prenylflavonoid (EP) Extract for Osteoporosis and Cardiovascular Disease
Official title: 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.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Osteoporosis
Cardiovascular Disease
Keywords: Epimedium prenylflavonoids
Osteoporosis
Cardiovascular diseases
Phase 1
safety
tolerability
Lead sponsor: National University Hospital, Singapore
Sponsor class: OTHER
First posted: 2016-10-13
Enrollment: 30
Sex: MALE
Minimum age (years): 21
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Healthy men.

Exclusion Criteria:

* Hepatitis B patients

Primary outcomes:
measure: Incidence and severity of adverse events/serious adverse events
timeFrame: 8 to10 days
Secondary outcomes:
measure: lcariin
timeFrame: 3 months
measure: Ex vivo osteoblast and osteoclast activities
timeFrame: 6 to 9 months
measure: Estrogenic biomarkers
timeFrame: 1 to 2 months
measure: interleukin-6 (IL-6)
timeFrame: 1 month
measure: high-sensitivity C-reactive protein (hs-CRP)
timeFrame: 1 month
measure: F2-isoprostanes
timeFrame: 1 month
measure: multiple platelet aggregation
timeFrame: 1 month
measure: Icaritin (ICT)
timeFrame: 3 months
measure: Demethylicaritin (DICT)
timeFrame: 3 months
measure: icariside 1
timeFrame: 3 months
measure: icariside II
timeFrame: 3 months
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: Investigational Medicine Unit, National University Health System
Study officials:
affiliation: National University Hospital, Singapore
name: Eu Leong Yong, MD & PhD
role: PRINCIPAL_INVESTIGATOR
References: