Third Year Evaluation on Genistein Efficacy and Safety

NCT ID: NCT00626769

Last Updated: 2009-05-19

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 138 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2005-07-31
• Study Completion Date: 2006-09-30

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).

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.

Conditions

Menopause; Osteopenia

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

1

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

aglycone genistein

Intervention Type: DIETARY_SUPPLEMENT

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

2

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

placebo

Intervention Type: DIETARY_SUPPLEMENT

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

Interventions

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.

Intervention Type: DIETARY_SUPPLEMENT

placebo

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

Intervention Type: DIETARY_SUPPLEMENT

Other Intervention Names

Genivis; Fosteum

Eligibility Criteria

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

• Minimum Eligible Age: 49 Years
• Maximum Eligible Age: 67 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Primus Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

University of Messina

OTHER

Sponsor Role: lead

Responsible Party

University of Messina

Principal Investigators

Francesco Squadrito, MD

Role: PRINCIPAL_INVESTIGATOR

University of Messina

Rosario D'Anna, MD

Role: STUDY_DIRECTOR

University of Messina

References

Marini H, Minutoli L, Polito F, Bitto A, Altavilla D, Atteritano M, Gaudio A, Mazzaferro S, Frisina A, Frisina N, Lubrano C, Bonaiuto M, D'Anna R, Cannata ML, Corrado F, Adamo EB, Wilson S, Squadrito F. Effects of the phytoestrogen genistein on bone metabolism in osteopenic postmenopausal women: a randomized trial. Ann Intern Med. 2007 Jun 19;146(12):839-47. doi: 10.7326/0003-4819-146-12-200706190-00005.

Reference Type: BACKGROUND

PMID: 17577003 (View on PubMed)

Bitto A, Polito F, Atteritano M, Altavilla D, Mazzaferro S, Marini H, Adamo EB, D'Anna R, Granese R, Corrado F, Russo S, Minutoli L, Squadrito F. Genistein aglycone does not affect thyroid function: results from a three-year, randomized, double-blind, placebo-controlled trial. J Clin Endocrinol Metab. 2010 Jun;95(6):3067-72. doi: 10.1210/jc.2009-2779. Epub 2010 Mar 31.

Reference Type: DERIVED

PMID: 20357174 (View on PubMed)

Marini H, Bitto A, Altavilla D, Burnett BP, Polito F, Di Stefano V, Minutoli L, Atteritano M, Levy RM, D'Anna R, Frisina N, Mazzaferro S, Cancellieri F, Cannata ML, Corrado F, Frisina A, Adamo V, Lubrano C, Sansotta C, Marini R, Adamo EB, Squadrito F. Breast safety and efficacy of genistein aglycone for postmenopausal bone loss: a follow-up study. J Clin Endocrinol Metab. 2008 Dec;93(12):4787-96. doi: 10.1210/jc.2008-1087. Epub 2008 Sep 16.

Reference Type: DERIVED

PMID: 18796517 (View on PubMed)

Other Identifiers

2005-07

Identifier Type: -

Identifier Source: org_study_id