Third Year Evaluation on Genistein Efficacy and Safety

Sponsor

University of Messina (Other)

Overall Status

Completed

CT.gov ID

NCT00626769

Collaborator

Primus Pharmaceuticals (Industry)

138

Enrollment

Duration (Months)

Study Details

Study Description

Brief Summary

BACKGROUND: Recent evidences showed that the phytoestrogen genistein positively affects bone metabolism with no clinically significant adverse effects in a cohort of osteopenic, postmenopausal women. However, there is still a knowledge gap regarding the long-term safety of genistein on the breast, the uterus, the thyroid gland and its efficacy in postmenopausal women.

OBJECTIVE: To assess the safety profile of genistein on mammary and thyroid glands and endometrium and cardiovascular apparatus and its effects on bone metabolism after a 3-year therapy with pure, standardized genistein (54 mg/day).

Condition or Disease	Intervention/Treatment	Phase
Menopause Osteopenia	Dietary Supplement: aglycone genistein Dietary Supplement: placebo

Detailed Description

DESIGN: The parent study was a randomized, double-blind, placebo-controlled trial involving 389 osteopenic, postmenopausal women for 24 months. After the 24-month visit, a sub-population (138 patients) accepted to continue the intervention until 36 months, thus generating a follow-up study.

SETTING: 3 Italian university medical centers. INTERVENTIONS: Participants received 54 mg of genistein, daily, (n=71) or placebo (n=67). Both intervention and placebo contained calcium and vitamin D3. All patients also received dietary instruction in an isocaloric fat-reduced diet.

MEASUREMENTS: Mammographic breast density at baseline and after 24 and 36 months was assessed by visual classification scale and by digitized quantification. BRCA1 and BRCA2 molecular message, sister chromatid exchanges and endometrial thickness were also evaluated at the same time points. Measurements of lumbar spine and femoral neck BMD and QUS t-score were assayed in our patients. Secondary outcomes were serum levels of B-ALP, IGF-I, sRANKL, osteoprotegerin and urinary excretion of CTX, pyridinoline and deoxypyridinoline. Furthermore insulin resistance (HOMA-IR), glucose levels, homocysteine and hot flushes were also evaluated. In addition for thyroid safety TSH, fT3, fT4, thyroid autoantibodies, and mRNA for thyroid and retinoid receptors were evaluated.

Study Design

Study Type:

Observational

Actual Enrollment :

138 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Safety Profile and Bone Efficacy of the Phytoestrogen Genistein in a Cohort of Osteopenic, Postmenopausal Women After Three Years of Treatment: a Follow-up Study

Study Start Date :

Jul 1, 2005

Actual Primary Completion Date :

Jul 1, 2006

Actual Study Completion Date :

Sep 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
1 Postmenopausal women with established osteopenia receiving aglycone genistein 54 mg/day for 3 years	Dietary Supplement: aglycone genistein 2 capsules per day containing 27 mg of aglycone genistein, calcium carbonate (500 mg) and vitamin D (400 IU), for a 3-year period. Other Names: Genivis Fosteum
2 Postmenopausal women with established osteopenia receiving placebo (Calcium and vitD) for 3 years	Dietary Supplement: placebo 2 capsules per day containing calcium carbonate (500 mg) and vitamin D (400 IU), for a 3-year period.

Arm

Intervention/Treatment

Postmenopausal women with established osteopenia receiving aglycone genistein 54 mg/day for 3 years

Dietary Supplement: aglycone genistein

2 capsules per day containing 27 mg of aglycone genistein, calcium carbonate (500 mg) and vitamin D (400 IU), for a 3-year period.

Other Names:

Genivis

Fosteum

Postmenopausal women with established osteopenia receiving placebo (Calcium and vitD) for 3 years

Dietary Supplement: placebo

2 capsules per day containing calcium carbonate (500 mg) and vitamin D (400 IU), for a 3-year period.

Outcome Measures

Primary Outcome Measures

Bone Mineral Density [basal and after 1 year]
Mammographic breast density [basal and after 3 years]

Secondary Outcome Measures

Bone-specific alkaline phosphatase (B-ALP) [basal and after 1 year]
Insulin-like growth factor 1 (IGF-1) [basal and after 1 year]
Pyridinium cross-links (pyridinoline and deoxypyridinoline) [basal and after 1 year]
carboxy-terminal cross-linking telopeptide (CTX) [basal and after 1 year]
Osteoprotegerin and soluble receptor activator of NF-kB ligand (s-RANKL) [basal and after 1 year]
BRCA1 and BRCA2 mRNA levels [basal and after 3 years]
Sister Chromatid exchanges [basal and after 3 years]
Endometrial thickness [basal and after 3 years]
Insulin resistance [basal and after 3 years]
hot flushes [basal and after 3 years]
Thyroid status [basal and after 3 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

49 Years to 67 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Good general health
Have not had a menstrual period in the preceding year
Had not undergone surgically induced menopause
Had a follicle-stimulating hormone level > 50 IU/liter and a serum 17 beta-estradiol level ≤ 100 pmol/liter
Established osteopenia (-1<T-score<-2.5 SD)

Exclusion Criteria:

Clinical or laboratory evidence of confounding systemic diseases, such as cardiovascular, hepatic, or renal disorders
Coagulopathy, use of oral or transdermal estrogen, progestin, androgen or other steroids
Biphosphonates, cholesterol-lowering therapy or cardiovascular medications in the preceding six months
Smoking habit of more than two cigarettes per day
Previous treatment with any drug that could affect the skeleton in the preceding year
A family history of estrogen-dependent cancer
BMD at femoral neck > 0.795 g/cm2; this BMD value corresponds to a T score of -1 standard deviation