Epimedium Prenylflavonoid (EP) Extract for Osteoporosis and Cardiovascular Disease

Phase 1

• Conditions: Osteoporosis; Cardiovascular Disease
• Interventions: Drug: Epimedium Prenylflavonoids Extract; Drug: Placebo

• Registration Number: NCT02931305
• Lead Sponsor: National University Hospital, Singapore

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.

Study Timeline

• Status Verified: 2016-10
• Study Start: 2016-10
• Study First Submitted: 2016-10-06
• Study First Submitted QC: 2016-10-10
• Last Update Submitted: 2016-10-12
• Study First Posted: 2016-10-13
• Last Update Posted: 2016-10-14
• Primary Completion: 2017-01
• Study Completion: 2017-10

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Male
• Target Recruitment: 30

Inclusion Criteria

• Healthy men.

Exclusion Criteria

• Hepatitis B patients

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Epimedium Prenylflavonoids Extract	Epimedium Prenylflavonoids Extract	Single oral doses of EP (370 mg, 740 mg and 1110 mg) capsules would be orally administered.
Placebo	Placebo	Single oral doses of Placebo (370 mg, 740 mg and 1110 mg) capsules would be orally administered.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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
Demethylicaritin (DICT)	3 months	Serum will be extracted from blood samples for measurement of levels of DICT using LC/MS.
lcariin	3 months	Serum will be extracted from blood samples for measurement of levels of icariin using Liquid chromatography-mass spectrometry (LC/MS).
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
multiple platelet aggregation	1 month	multiple platelet aggregation assays for thrombosis
Icaritin (ICT)	3 months	Serum will be extracted from blood samples for measurement of levels of ICT 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.

Trial Locations

Locations (1)

Investigational Medicine Unit, National University Health System; 🇸🇬 Singapore, Singapore