Isoflavone Treatment for Postmenopausal Osteopenia.

Study Overview
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Brief Summary
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The aim of the project is to execute a double-blind, parallel, randomized 12-month intervention trial on postmenopausal women with osteopenia (low bone mineral density), in order to determine the effects of daily intake of fermented red clover (RC) extract on estrogen dependent bone mineral resorption when compared to placebo. Both groups will recieve equivalent daily calcium, vitamin D and magnesium supplements. The project will also assess whether bioactive compounds in RC can reduce the risk of developing cardiovascular disease.

Detailed Description
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The project aims to determine whether red clover derived isoflavones have capabilities to exert positive effects in conditions of osteoporosis and osteopenia in states estrogen deficiency and/or dysregulation. The cause of osteopenia in women is thought to arise from the deficiency of and/or dysregulation by estrogen on target tissues. Hormone Replacement Therapy (HRT) has proven to be an effective treatment, however it retains limited use as there is general consensus that it also increases cancer risk. Plant derived compounds that emulate the chemical structure and behaviour of estrogen (known as isoflavones) offer a compelling alternative to HRT, due to their potential to adopt the regulatory roles of estrogen without incurring equivalent negative side effects of HRT. There are, at present, few or no direct head to head clinical trials assessing combination treatments of isoflavones, vitamin D and calcium in contrast to standard vitamin D and calcium supplementation proscribed to osteopenic patients. Research in this area will therefore provide valuable insight into the effectiveness of isoflavones to reduce resorption and/or to stimulate the formation of bone tissue. Moreover the study will provide a comprehensive assessment of the potential of isoflavones to enhance the efficacy of existing preventative treatments. Outcomes of the project have the prospect to help thousands of middle aged and PM women suffering. Moreover, the project may enable development of functional foods and/or nutraceuticals that can be used as either a preventative measure and/or as a treatment for osteoporosis in states of estrogen deficiency and thereby provide an alternative to Hormone Replacement Therapy that does involve the same side effects and risks.

Official Title
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The Effects of Red Clover Treatment on Bone Tissue Regulation in Postmenopausal Osteopenia.

Conditions
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Osteopenia, Osteoporosis

Intervention / Treatment
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* Dietary Supplement: Red clover extract
* Dietary Supplement: Supplementation (placebo)


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Age 50-85 years, only women Have osteopenia (T score between -1 and -2.5) Body Mass Index (BMI) between 20 and 40 Exclusion criteria: Taken specific osteoporosis drugs (i.e. bisphosphonates, PTH, estrogen or strontium ranelate) in the past 3 months Taken other selective estrogen receptor modulator preparations (raloxifene, tamoxifen or isoflavones) in the past 3 months Participation in other clinical trials within the last 3 months Previous history of cardiovascular, psychiatric, neurological, and / or kidney disease Alcohol or substance abuse or acute illness Blood pressure> 160/110 Pregnant and breastfeeding women

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Red clover extract<br>Group recieving daily red clover extract containing isoflavones (80 mg/d), along with calcium (1040 mg/d), vitamin D (25µg/d) and magnesium (487mg/d). | Dietary Supplement: Red clover extract<br>* Aglycone isoflavones 80mg/d<br>* Other names: Calcium;|
| Placebo Comparator: Placebo group<br>Group recieving daily placebo extract (with no isoflavone content), calcium (1040 mg/d), vitamin D (25µg/d) and magnesium (487mg/d). | Dietary Supplement: Supplementation (placebo)<br> <br> * Other names: Calcuim;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma C-terminal telopeptide (CTX) | Bone mineral resorption biomarker. | 0 - 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone mineral density via dual energy X-ray absorptiometry | Objective measure of bone mineral density and bone mineral content. | 0 - 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aglycones, Isoflavones, Red clover, Osteopenia, Menopause, Bone turnover, Bone mineral density