Third Year Evaluation on Genistein Efficacy and Safety

Menopause Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00626769
• Other study ID #: 2005-07
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: February 19, 2008
• Last updated: May 18, 2009
• Start date: July 2005
• Est. completion date: September 2006

Study information

• Verified date: May 2009
• Source: University of Messina
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ethics Committee
• Study type: Observational

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 138
• Est. completion date: September 2006
• Est. primary completion date: July 2006
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 49 Years to 67 Years

Eligibility

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

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Menopause
• Osteopenia

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
University of Messina	Primus Pharmaceuticals

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Bone Mineral Density		basal and after 1 year	No
Primary	Mammographic breast density		basal and after 3 years	Yes
Secondary	Bone-specific alkaline phosphatase (B-ALP)		basal and after 1 year	No
Secondary	Insulin-like growth factor 1 (IGF-1)		basal and after 1 year	No
Secondary	Pyridinium cross-links (pyridinoline and deoxypyridinoline)		basal and after 1 year	No
Secondary	carboxy-terminal cross-linking telopeptide (CTX)		basal and after 1 year	No
Secondary	Osteoprotegerin and soluble receptor activator of NF-kB ligand (s-RANKL)		basal and after 1 year	No
Secondary	BRCA1 and BRCA2 mRNA levels		basal and after 3 years	Yes
Secondary	Sister Chromatid exchanges		basal and after 3 years	Yes
Secondary	Endometrial thickness		basal and after 3 years	Yes
Secondary	Insulin resistance		basal and after 3 years	No
Secondary	hot flushes		basal and after 3 years	Yes
Secondary	Thyroid status		basal and after 3 years	Yes