Epimedium Prenylflavonoid (EP) Extract for Osteoporosis and Cardiovascular Disease

October 12, 2016 updated by: Obstetrics & Gynaecology, National University Hospital, Singapore

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.

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

30

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years to 45 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Healthy men.

Exclusion Criteria:

  • Hepatitis B patients

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Epimedium Prenylflavonoids Extract
Single oral doses of EP (370 mg, 740 mg and 1110 mg) capsules would be orally administered.
Drug: Epimedium Prenylflavonoids Extract
Each Epimedium Prenylflavonoids Extract capsule contains 370 mg of EPIMEDIUM EXTRACT
Other Names:
  • EP
Placebo Comparator: Placebo
Single oral doses of Placebo (370 mg, 740 mg and 1110 mg) capsules would be orally administered.
Drug: Placebo
Use iron oxide (brown, black and yellow) to mimic Epimedium Prenylflavonoids Extract.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence and severity of adverse events/serious adverse events
Time Frame: 8 to10 days
Incidence and severity of adverse events/serious adverse events based on history, physical examination and vital signs, hematology and clinical chemistry.
8 to10 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
lcariin
Time Frame: 3 months
Serum will be extracted from blood samples for measurement of levels of icariin using Liquid chromatography-mass spectrometry (LC/MS).
3 months
Ex vivo osteoblast and osteoclast activities
Time Frame: 6 to 9 months
Ex vivo assays using human serum to test the effects of EP in bone models of osteoblasts and osteoclasts
6 to 9 months
Estrogenic biomarkers
Time Frame: 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.
1 to 2 months
interleukin-6 (IL-6)
Time Frame: 1 month
IL-6 assays for thrombosis
1 month
high-sensitivity C-reactive protein (hs-CRP)
Time Frame: 1 month
hs-CRP assays for thrombosis
1 month
F2-isoprostanes
Time Frame: 1 month
F2-isoprostanes assays for thrombosis
1 month
multiple platelet aggregation
Time Frame: 1 month
multiple platelet aggregation assays for thrombosis
1 month
Icaritin (ICT)
Time Frame: 3 months
Serum will be extracted from blood samples for measurement of levels of ICT using LC/MS.
3 months
Demethylicaritin (DICT)
Time Frame: 3 months
Serum will be extracted from blood samples for measurement of levels of DICT using LC/MS.
3 months
icariside 1
Time Frame: 3 months
Serum will be extracted from blood samples for measurement of levels of icariside 1 using LC/MS.
3 months
icariside II
Time Frame: 3 months
Serum will be extracted from blood samples for measurement of levels of icariside II using LC/MS.
3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National University Hospital, Singapore

Investigators

  • Principal Investigator: Eu Leong Yong, MD & PhD, National University Hospital, Singapore

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2016

Primary Completion (Anticipated)

January 1, 2017

Study Completion (Anticipated)

October 1, 2017

Study Registration Dates

First Submitted

October 6, 2016

First Submitted That Met QC Criteria

October 10, 2016

First Posted (Estimate)

October 13, 2016

Study Record Updates

Last Update Posted (Estimate)

October 14, 2016

Last Update Submitted That Met QC Criteria

October 12, 2016

Last Verified

October 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EP2016

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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