Cardiovascular Disease, Osteoporosis
Conditions
Keywords
Epimedium prenylflavonoids, Osteoporosis, Cardiovascular diseases, Phase 1, safety, tolerability
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.
Interventions
DRUGEpimedium Prenylflavonoids Extract
Each Epimedium Prenylflavonoids Extract capsule contains 370 mg of EPIMEDIUM EXTRACT
DRUGPlacebo
Use iron oxide (brown, black and yellow) to mimic Epimedium Prenylflavonoids Extract.
Sponsors
National University Hospital, Singapore
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
21 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy men.
Exclusion criteria
* Hepatitis B patients
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and severity of adverse events/serious adverse events | 8 to10 days | Incidence and severity of adverse events/serious adverse events based on history, physical examination and vital signs, hematology and clinical chemistry. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ex vivo osteoblast and osteoclast activities | 6 to 9 months | Ex vivo assays using human serum to test the effects of EP in bone models of osteoblasts and osteoclasts |
| Estrogenic biomarkers | 1 to 2 months | The serum will be tested for cell based estrogen receptor bioassays, and its effects on Michigan Cancer Foundation-7 (MCF-7) cell proliferation will also be assessed. |
| interleukin-6 (IL-6) | 1 month | IL-6 assays for thrombosis |
| high-sensitivity C-reactive protein (hs-CRP) | 1 month | hs-CRP assays for thrombosis |
| F2-isoprostanes | 1 month | F2-isoprostanes assays for thrombosis |
| lcariin | 3 months | Serum will be extracted from blood samples for measurement of levels of icariin using Liquid chromatography-mass spectrometry (LC/MS). |
| Icaritin (ICT) | 3 months | Serum will be extracted from blood samples for measurement of levels of ICT using LC/MS. |
| Demethylicaritin (DICT) | 3 months | Serum will be extracted from blood samples for measurement of levels of DICT using LC/MS. |
| icariside 1 | 3 months | Serum will be extracted from blood samples for measurement of levels of icariside 1 using LC/MS. |
| icariside II | 3 months | Serum will be extracted from blood samples for measurement of levels of icariside II using LC/MS. |
| multiple platelet aggregation | 1 month | multiple platelet aggregation assays for thrombosis |
Countries
Singapore
Contacts
Primary ContactEu Leong Yong, MD & PhD
Outcome results
None listed