Clinical trial NCT01232751: Effects of Isoflavones on Gene-expression
Official title: The Effect of Isoflavone Supplement Intake on Gene-expression in Postmenopausal Women
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Postmenopause
Keywords: health
women
Lead sponsor: Wageningen University
Sponsor class: OTHER
First posted: 2010-11-02
Enrollment: 30
Sex: FEMALE
Minimum age (years): 45
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER

Brief summary: Alleged benefits experienced by the consumption of soy in Asian countries have been attributed to the isoflavone content of soy products. Amongst other benefits, isoflavones are believed to relieve menopausal symptoms and are therefore often consumed in supplement form in Western countries. These supplements contain relatively high amounts of isoflavones, and the question is if these concentrations still exert beneficial effects or whether negative effects become dominant. Therefore, the investigators will study the effect of intake of one dose of isoflavones, as compared to placebo, for eight weeks on gene-expression in Peripheral Blood Mononuclear Cells (PBMCs) in post-menopausal, equol-producing women.

Detailed description: Primary Objective: to determine the effect of intake of one dose of isoflavones, as compared to placebo, for eight weeks on gene-expression in Peripheral Blood Mononuclear Cells (PBMCs) in post-menopausal, equol-producing women.

Secondary Objectives: to determine the association between isoflavone plasma levels and gene-expression in PBMCs; to determine the variation of isoflavone plasma levels between subjects after intake of isoflavones for four and eight weeks; to explore whether PBMC gene-expression markers identified after 8 weeks isoflavone intervention are already present after 4 weeks intervention; to explore whether the severity of previous menopausal complaints is related to the effect of isoflavones on PBMC gene-expression; and to explore the association between isoflavone levels in plasma and spot urine.

Study design: Double-blind placebo controlled crossover intervention study

Study population: Thirty-six healthy females, 45-70 years, post-menopausal and equol-producing

Intervention: Two intervention periods of eight weeks with a isoflavone supplement or a placebo and a washout period of 8 weeks in between.

Main study parameters/endpoints: The main study parameter is gene-expression in PBMCs measured by micro-arrays.

Eligibility criteria: Inclusion Criteria:

* 45-70 years
* Equol producer
* Post-menopausal (Follicle Stimulating Hormone (FSH) \>40 UI/L) or
* menstrual cycle absent for more than 1 year.

Exclusion Criteria:

* current use of contraceptives containing hormones
* current use of hormone replacement therapy
* regular soy product use (more than once a week)
* regular isoflavone supplement use (more than once a week)
* current use of medication containing sex hormones or sex hormone-triggering compounds
* current use of anti-inflammatory medicines
* use of antibiotics in the past 6 months
* severe heart disease
* thyroid disorders
* removed thyroid gland
* complete ovariectomy
* prior diagnosis of cancer in medical history
* alcohol and drug abuse
* current smoker
* Body Mass Index (BMI) \>35 kg/m2
* allergy to soy (products)

Primary outcomes:
measure: Gene-expression measured by micro-arrays
timeFrame: gene-expression after 8 weeks of exposure to the isoflavone supplement
measure: Gene-expression measured by micro-arrays
timeFrame: after 8 weeks of exposure to the placebo
Secondary outcomes:
measure: Isoflavone levels in plasma and spoturine
timeFrame: after 0 weeks of exposure to the isoflavone supplement
measure: Isoflavone levels in plasma and spoturine
timeFrame: after 4 weeks of exposure to the isoflavone supplement
measure: Isoflavone levels in plasma and spoturine
timeFrame: after 8 weeks of exposure to the isoflavone supplement
measure: Isoflavone levels in plasma and spoturine
timeFrame: after 0 weeks of exposure to the placebo
measure: Isoflavone levels in plasma and spoturine
timeFrame: after 4 weeks of exposure to the placebo
measure: Isoflavone levels in plasma and spoturine
timeFrame: after 8 weeks of exposure to the placebo
measure: Confirmation of gene-expression with quantitative real time polymerase chain reaction (QPCR)
timeFrame: after 0 weeks of exposure to the isoflavone supplement
measure: Confirmation of gene-expression with quantitative real time polymerase chain reaction (QPCR)
timeFrame: after 4 weeks of exposure to the isoflavone supplement
measure: Confirmation of gene-expression with quantitative real time polymerase chain reaction (QPCR)
timeFrame: after 0 weeks of exposure to the placebo
measure: Confirmation of gene-expression with quantitative real time polymerase chain reaction (QPCR)
timeFrame: after 8 weeks of exposure to the isoflavone supplement
measure: Confirmation of gene-expression with quantitative real time polymerase chain reaction (QPCR)
timeFrame: after 4 weeks of exposure to the placebo
measure: Confirmation of gene-expression with quantitative real time polymerase chain reaction (QPCR)
timeFrame: after 8 weeks of exposure to the placebo
Other outcomes:
Locations:
city: Wageningen
country: Netherlands
facility: Wageningen University
state: Gelderland
Study officials:
affiliation: Wageningen University
name: Pieter van 't Veer, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: van der Velpen V, Geelen A, Schouten EG, Hollman PC, Afman LA, van 't Veer P. Estrogen receptor-mediated effects of isoflavone supplementation were not observed in whole-genome gene expression profiles of peripheral blood mononuclear cells in postmenopausal, equol-producing women. J Nutr. 2013 Jun;143(6):774-80. doi: 10.3945/jn.113.174037. Epub 2013 Apr 24.