Effects of Isoflavones on Gene-expression (ISO)

January 9, 2012 updated by: Lisette de Groot, Wageningen University

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
    • Gelderland
      • Wageningen, Gelderland, Netherlands, 6703 HD
        • Wageningen University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

45 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Female

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
gene-expression after 8 weeks of exposure to the isoflavone supplement
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.
after 8 weeks of exposure to the placebo

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
after 0 weeks of exposure to the isoflavone supplement
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.
after 4 weeks of exposure to the isoflavone supplement
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.
after 8 weeks of exposure to the isoflavone supplement
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.
after 0 weeks of exposure to the placebo
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.
after 4 weeks of exposure to the placebo
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.
after 8 weeks of exposure to the placebo
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.
after 0 weeks of exposure to the isoflavone supplement
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.
after 4 weeks of exposure to the isoflavone supplement
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.
after 0 weeks of exposure to the placebo
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.
after 8 weeks of exposure to the isoflavone supplement
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.
after 4 weeks of exposure to the placebo
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.
after 8 weeks of exposure to the placebo

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Wageningen University

Investigators

  • Principal Investigator: Pieter van 't Veer, Professor, Wageningen University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2010

Primary Completion (Actual)

October 1, 2011

Study Completion (Actual)

October 1, 2011

Study Registration Dates

First Submitted

October 21, 2010

First Submitted That Met QC Criteria

November 1, 2010

First Posted (Estimate)

November 2, 2010

Study Record Updates

Last Update Posted (Estimate)

January 10, 2012

Last Update Submitted That Met QC Criteria

January 9, 2012

Last Verified

January 1, 2012

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • NL 32375.081.10

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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