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Completed

NCT Number: NCT01232751

Effects of Isoflavones on Gene-expression

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.

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Key information

Conditions

Postmenopause

Age range

45 year–70 year

Sex eligibility

Female

Study type

Interventional

Phase

Not applicable

Primary location

Wageningen University

Wageningen, Gelderland, 6703 HD, Netherlands

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

Isoflavone supplement

Dietary Supplement

The participants will consume 2 times 2 supplements per day, which will lead to a daily dose of 114 mg. (HPLC analysis confirmed an aglycone isoflavone content of 28.41 mg per supplement)

Other names: Phytosoya forte (35mg) from the company Arkopharma

Primary outcomes

  1. Gene-expression measured by micro-arrays

    Time frame: gene-expression after 8 weeks of exposure to the isoflavone supplement

    Gene expression changes will be assessed in PBMCs using whole genome Affymetrix microarrays. The gene expression changes after exposure to the isoflavone supplement will be compared to the changes after exposure to the placebo.

  2. Gene-expression measured by micro-arrays

    Time frame: after 8 weeks of exposure to the placebo

    Gene expression changes will be assessed in PBMCs using whole genome Affymetrix microarrays. The gene expression changes after exposure to the isoflavone supplement will be compared to the changes after exposure to the placebo.

Secondary outcomes

  1. Isoflavone levels in plasma and spoturine

    Time frame: after 0 weeks of exposure to the isoflavone supplement

    levels of the isoflavones genistein, dihydrogenistein, daidzein, dihydrodaidzein, equol and glycitein will be measured with High performance liquid chromatography (HPLC). Following the intention to treat analysis, these concentration markers will be determined in order to correlate the gene-expression measured with quantitative real-time polymerase chain reaction (QPCR) with the isoflavone plasma levels, and to stratify for the plasma levels in per protocol analysis.

  2. Isoflavone levels in plasma and spoturine

    Time frame: after 4 weeks of exposure to the isoflavone supplement

    levels of the isoflavones genistein, dihydrogenistein, daidzein, dihydrodaidzein, equol and glycitein will be measured with HPLC. Following the intention to treat analysis, these concentration markers will be determined in order to correlate the gene-expression measured with QPCR with the isoflavone plasma levels, and to stratify for the plasma levels in per protocol analysis.

  3. Isoflavone levels in plasma and spoturine

    Time frame: after 8 weeks of exposure to the isoflavone supplement

    levels of the isoflavones genistein, dihydrogenistein, daidzein, dihydrodaidzein, equol and glycitein will be measured with HPLC. Following the intention to treat analysis, these concentration markers will be determined in order to correlate the gene-expression measured with QPCR with the isoflavone plasma levels, and to stratify for the plasma levels in per protocol analysis.

  4. Isoflavone levels in plasma and spoturine

    Time frame: after 0 weeks of exposure to the placebo

    levels of the isoflavones genistein, dihydrogenistein, daidzein, dihydrodaidzein, equol and glycitein will be measured with HPLC. Following the intention to treat analysis, these concentration markers will be determined in order to correlate the gene-expression measured with QPCR with the isoflavone plasma levels, and to stratify for the plasma levels in per protocol analysis.

  5. Isoflavone levels in plasma and spoturine

    Time frame: after 4 weeks of exposure to the placebo

    levels of the isoflavones genistein, dihydrogenistein, daidzein, dihydrodaidzein, equol and glycitein will be measured with HPLC. Following the intention to treat analysis, these concentration markers will be determined in order to correlate the gene-expression measured with QPCR with the isoflavone plasma levels, and to stratify for the plasma levels in per protocol analysis.

  6. Isoflavone levels in plasma and spoturine

    Time frame: after 8 weeks of exposure to the placebo

    levels of the isoflavones genistein, dihydrogenistein, daidzein, dihydrodaidzein, equol and glycitein will be measured with HPLC. Following the intention to treat analysis, these concentration markers will be determined in order to correlate the gene-expression measured with QPCR with the isoflavone plasma levels, and to stratify for the plasma levels in per protocol analysis.

  7. Confirmation of gene-expression with quantitative real time polymerase chain reaction (QPCR)

    Time frame: after 0 weeks of exposure to the isoflavone supplement

    Ten genes per sample will be verified with QPCR. PBMCs from the subjects are available at time points before, halfway and after the two intervention periods. On the basis of the micro-array results it will be decided which genes from which samples will be quantified.

  8. Confirmation of gene-expression with quantitative real time polymerase chain reaction (QPCR)

    Time frame: after 4 weeks of exposure to the isoflavone supplement

    Ten genes per sample will be verified with QPCR. PBMCs from the subjects are available at time points before, halfway and after the two intervention periods. On the basis of the micro-array results it will be decided which genes from which samples will be quantified.

  9. Confirmation of gene-expression with quantitative real time polymerase chain reaction (QPCR)

    Time frame: after 0 weeks of exposure to the placebo

    Ten genes per sample will be verified with QPCR. PBMCs from the subjects are available at time points before, halfway and after the two intervention periods. On the basis of the micro-array results it will be decided which genes from which samples will be quantified.

  10. Confirmation of gene-expression with quantitative real time polymerase chain reaction (QPCR)

    Time frame: after 8 weeks of exposure to the isoflavone supplement

    Ten genes per sample will be verified with QPCR. PBMCs from the subjects are available at time points before, halfway and after the two intervention periods. On the basis of the micro-array results it will be decided which genes from which samples will be quantified.

  11. Confirmation of gene-expression with quantitative real time polymerase chain reaction (QPCR)

    Time frame: after 4 weeks of exposure to the placebo

    Ten genes per sample will be verified with QPCR. PBMCs from the subjects are available at time points before, halfway and after the two intervention periods. On the basis of the micro-array results it will be decided which genes from which samples will be quantified.

  12. Confirmation of gene-expression with quantitative real time polymerase chain reaction (QPCR)

    Time frame: after 8 weeks of exposure to the placebo

    Ten genes per sample will be verified with QPCR. PBMCs from the subjects are available at time points before, halfway and after the two intervention periods. On the basis of the micro-array results it will be decided which genes from which samples will be quantified.

Sponsors and collaborators

Lead sponsor

Wageningen University

Other

Registry information

Official study title

The Effect of Isoflavone Supplement Intake on Gene-expression in Postmenopausal Women

Acronym: ISO

Important dates

Study start
2010
Primary completion
2011
Study completion
2011
First posted
Nov 2, 2010
Registry last updated
Jan 10, 2012

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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