Epimedium Prenylflavonoid (EP) Extract for Osteoporosis and Cardiovascular Disease

Osteoporosis Clinical Trial

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02931305
• Other study ID #: EP2016
• Status: Recruiting
• Phase: Phase 1
• First received: October 6, 2016
• Last updated: October 12, 2016
• Start date: October 2016
• Est. completion date: October 2017

Study information

• Verified date: October 2016
• Source: National University Hospital, Singapore
• Contact: Eu Leong Yong, MD & PhD
• Phone: 67724285
• Email: obgyel[@]nus.edu.sg
• Is FDA regulated: No
• Health authority: Singapore: Domain Specific Review BoardsSingapore: Health Sciences Authority
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: October 2017
• Est. primary completion date: January 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 21 Years to 45 Years

Eligibility

Inclusion Criteria:

• Healthy men.

Exclusion Criteria:

• Hepatitis B patients

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cardiovascular Disease
• Cardiovascular Diseases
• Osteoporosis

Intervention

Drug:
• Epimedium Prenylflavonoids Extract
Each Epimedium Prenylflavonoids Extract capsule contains 370 mg of EPIMEDIUM EXTRACT
• Placebo
Use iron oxide (brown, black and yellow) to mimic Epimedium Prenylflavonoids Extract.

Locations

Country	Name	City	State
Singapore	Investigational Medicine Unit, National University Health System	Singapore

Sponsors (1)

Lead Sponsor	Collaborator
National University Hospital, Singapore

Country where clinical trial is conducted

Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence and severity of adverse events/serious adverse events	Incidence and severity of adverse events/serious adverse events based on history, physical examination and vital signs, hematology and clinical chemistry.	8 to10 days	Yes
Secondary	lcariin	Serum will be extracted from blood samples for measurement of levels of icariin using Liquid chromatography-mass spectrometry (LC/MS).	3 months	No
Secondary	Ex vivo osteoblast and osteoclast activities	Ex vivo assays using human serum to test the effects of EP in bone models of osteoblasts and osteoclasts	6 to 9 months	No
Secondary	Estrogenic biomarkers	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.	1 to 2 months	No
Secondary	interleukin-6 (IL-6)	IL-6 assays for thrombosis	1 month	No
Secondary	high-sensitivity C-reactive protein (hs-CRP)	hs-CRP assays for thrombosis	1 month	No
Secondary	F2-isoprostanes	F2-isoprostanes assays for thrombosis	1 month	No
Secondary	multiple platelet aggregation	multiple platelet aggregation assays for thrombosis	1 month	No
Secondary	Icaritin (ICT)	Serum will be extracted from blood samples for measurement of levels of ICT using LC/MS.	3 months	No
Secondary	Demethylicaritin (DICT)	Serum will be extracted from blood samples for measurement of levels of DICT using LC/MS.	3 months	No
Secondary	icariside 1	Serum will be extracted from blood samples for measurement of levels of icariside 1 using LC/MS.	3 months	No
Secondary	icariside II	Serum will be extracted from blood samples for measurement of levels of icariside II using LC/MS.	3 months	No