Third Year Evaluation on Genistein Efficacy and Safety

This study has been completed.
Sponsor:
Collaborator:
Primus Pharmaceuticals
Information provided by:
University of Messina
ClinicalTrials.gov Identifier:
NCT00626769
First received: February 19, 2008
Last updated: May 18, 2009
Last verified: May 2009
  Purpose

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 Intervention Phase
Menopause
Osteopenia
Dietary Supplement: aglycone genistein
Dietary Supplement: placebo
Phase 2
Phase 3

Study Type: Observational
Study Design: 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

Resource links provided by NLM:


Further study details as provided by University of Messina:

Primary Outcome Measures:
  • Bone Mineral Density [ Time Frame: basal and after 1 year ] [ Designated as safety issue: No ]
  • Mammographic breast density [ Time Frame: basal and after 3 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Bone-specific alkaline phosphatase (B-ALP) [ Time Frame: basal and after 1 year ] [ Designated as safety issue: No ]
  • Insulin-like growth factor 1 (IGF-1) [ Time Frame: basal and after 1 year ] [ Designated as safety issue: No ]
  • Pyridinium cross-links (pyridinoline and deoxypyridinoline) [ Time Frame: basal and after 1 year ] [ Designated as safety issue: No ]
  • carboxy-terminal cross-linking telopeptide (CTX) [ Time Frame: basal and after 1 year ] [ Designated as safety issue: No ]
  • Osteoprotegerin and soluble receptor activator of NF-kB ligand (s-RANKL) [ Time Frame: basal and after 1 year ] [ Designated as safety issue: No ]
  • BRCA1 and BRCA2 mRNA levels [ Time Frame: basal and after 3 years ] [ Designated as safety issue: Yes ]
  • Sister Chromatid exchanges [ Time Frame: basal and after 3 years ] [ Designated as safety issue: Yes ]
  • Endometrial thickness [ Time Frame: basal and after 3 years ] [ Designated as safety issue: Yes ]
  • Insulin resistance [ Time Frame: basal and after 3 years ] [ Designated as safety issue: No ]
  • hot flushes [ Time Frame: basal and after 3 years ] [ Designated as safety issue: Yes ]
  • Thyroid status [ Time Frame: basal and after 3 years ] [ Designated as safety issue: Yes ]

Biospecimen Retention:   Samples With DNA

whole blood, serum, plasma, urine.


Enrollment: 138
Study Start Date: July 2005
Study Completion Date: September 2006
Primary Completion Date: July 2006 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   49 Years to 67 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Postmenopausal women (age 49-67 yrs)

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00626769

Sponsors and Collaborators
University of Messina
Primus Pharmaceuticals
Investigators
Principal Investigator: Francesco Squadrito, MD University of Messina
Study Director: Rosario D'Anna, MD University of Messina
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Prof. Francesco Squadrito, University of Messina
ClinicalTrials.gov Identifier: NCT00626769     History of Changes
Other Study ID Numbers: 2005-07
Study First Received: February 19, 2008
Last Updated: May 18, 2009
Health Authority: Italy: Ethics Committee

Keywords provided by University of Messina:
Genistein
Bone mineral density
digital mammography
safety

Additional relevant MeSH terms:
Genistein
Anticarcinogenic Agents
Protective Agents
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Phytoestrogens
Estrogens, Non-Steroidal
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on October 19, 2014