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Epimedium Prenylflavonoid (EP) Extract for Osteoporosis and Cardiovascular Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02931305
Recruitment Status : Unknown
Verified October 2016 by Obstetrics & Gynaecology, National University Hospital, Singapore.
Recruitment status was:  Recruiting
First Posted : October 13, 2016
Last Update Posted : October 14, 2016
Sponsor:
Information provided by (Responsible Party):
Obstetrics & Gynaecology, 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.

Condition or disease Intervention/treatment Phase
Osteoporosis Cardiovascular Disease Drug: Epimedium Prenylflavonoids Extract Drug: Placebo Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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 Start Date : October 2016
Estimated Primary Completion Date : January 2017
Estimated Study Completion Date : October 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Osteoporosis

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 Name: 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.




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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).

  2. 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

  3. 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.

  4. interleukin-6 (IL-6) [ Time Frame: 1 month ]
    IL-6 assays for thrombosis

  5. high-sensitivity C-reactive protein (hs-CRP) [ Time Frame: 1 month ]
    hs-CRP assays for thrombosis

  6. F2-isoprostanes [ Time Frame: 1 month ]
    F2-isoprostanes assays for thrombosis

  7. multiple platelet aggregation [ Time Frame: 1 month ]
    multiple platelet aggregation assays for thrombosis

  8. Icaritin (ICT) [ Time Frame: 3 months ]
    Serum will be extracted from blood samples for measurement of levels of ICT using LC/MS.

  9. Demethylicaritin (DICT) [ Time Frame: 3 months ]
    Serum will be extracted from blood samples for measurement of levels of DICT using LC/MS.

  10. icariside 1 [ Time Frame: 3 months ]
    Serum will be extracted from blood samples for measurement of levels of icariside 1 using LC/MS.

  11. icariside II [ Time Frame: 3 months ]
    Serum will be extracted from blood samples for measurement of levels of icariside II using LC/MS.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   21 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy men.

Exclusion Criteria:

  • Hepatitis B patients

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02931305


Contacts
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Contact: Eu Leong Yong, MD & PhD 67724285 obgyel@nus.edu.sg

Locations
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Singapore
Investigational Medicine Unit, National University Health System Recruiting
Singapore, Singapore, 117599
Contact: Pei Ling Tan    6601 2534    angelia_pei_ling_tan@nuhs.edu.sg   
Sponsors and Collaborators
National University Hospital, Singapore
Investigators
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Principal Investigator: Eu Leong Yong, MD & PhD National University Hospital, Singapore
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Responsible Party: Obstetrics & Gynaecology, Professor, National University Hospital, Singapore
ClinicalTrials.gov Identifier: NCT02931305    
Other Study ID Numbers: EP2016
First Posted: October 13, 2016    Key Record Dates
Last Update Posted: October 14, 2016
Last Verified: October 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by Obstetrics & Gynaecology, National University Hospital, Singapore:
Epimedium prenylflavonoids
Osteoporosis
Cardiovascular diseases
Phase 1
safety
tolerability
Additional relevant MeSH terms:
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Osteoporosis
Cardiovascular Diseases
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Metabolic Diseases