Effects of Isoflavones on Gene-expression (ISO)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Lisette de Groot, Wageningen University
ClinicalTrials.gov Identifier:
NCT01232751
First received: October 21, 2010
Last updated: January 9, 2012
Last verified: January 2012
  Purpose

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.


Condition Intervention
Postmenopause
Dietary Supplement: Isoflavone supplement

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Official Title: The Effect of Isoflavone Supplement Intake on Gene-expression in Postmenopausal Women

Resource links provided by NLM:


Further study details as provided by Wageningen University:

Primary Outcome Measures:
  • Gene-expression measured by micro-arrays [ Time Frame: gene-expression after 8 weeks of exposure to the isoflavone supplement ] [ Designated as safety issue: No ]
    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 measured by micro-arrays [ Time Frame: after 8 weeks of exposure to the placebo ] [ Designated as safety issue: No ]
    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 Outcome Measures:
  • Isoflavone levels in plasma and spoturine [ Time Frame: after 0 weeks of exposure to the isoflavone supplement ] [ Designated as safety issue: No ]
    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.

  • Isoflavone levels in plasma and spoturine [ Time Frame: after 4 weeks of exposure to the isoflavone supplement ] [ Designated as safety issue: No ]
    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.

  • Isoflavone levels in plasma and spoturine [ Time Frame: after 8 weeks of exposure to the isoflavone supplement ] [ Designated as safety issue: No ]
    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.

  • Isoflavone levels in plasma and spoturine [ Time Frame: after 0 weeks of exposure to the placebo ] [ Designated as safety issue: No ]
    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.

  • Isoflavone levels in plasma and spoturine [ Time Frame: after 4 weeks of exposure to the placebo ] [ Designated as safety issue: No ]
    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.

  • Isoflavone levels in plasma and spoturine [ Time Frame: after 8 weeks of exposure to the placebo ] [ Designated as safety issue: No ]
    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.

  • Confirmation of gene-expression with quantitative real time polymerase chain reaction (QPCR) [ Time Frame: after 0 weeks of exposure to the isoflavone supplement ] [ Designated as safety issue: No ]
    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.

  • Confirmation of gene-expression with quantitative real time polymerase chain reaction (QPCR) [ Time Frame: after 4 weeks of exposure to the isoflavone supplement ] [ Designated as safety issue: No ]
    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.

  • Confirmation of gene-expression with quantitative real time polymerase chain reaction (QPCR) [ Time Frame: after 0 weeks of exposure to the placebo ] [ Designated as safety issue: No ]
    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.

  • Confirmation of gene-expression with quantitative real time polymerase chain reaction (QPCR) [ Time Frame: after 8 weeks of exposure to the isoflavone supplement ] [ Designated as safety issue: No ]
    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.

  • Confirmation of gene-expression with quantitative real time polymerase chain reaction (QPCR) [ Time Frame: after 4 weeks of exposure to the placebo ] [ Designated as safety issue: No ]
    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.

  • Confirmation of gene-expression with quantitative real time polymerase chain reaction (QPCR) [ Time Frame: after 8 weeks of exposure to the placebo ] [ Designated as safety issue: No ]
    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.


Enrollment: 30
Study Start Date: August 2010
Study Completion Date: October 2011
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Intervention Details:
    Dietary Supplement: Isoflavone 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 Name: Phytosoya forte (35mg) from the company Arkopharma
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

Ages Eligible for Study:   45 Years to 70 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
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)
  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: NCT01232751

Locations
Netherlands
Wageningen University
Wageningen, Gelderland, Netherlands, 6703 HD
Sponsors and Collaborators
Wageningen University
Investigators
Principal Investigator: Pieter van 't Veer, Professor Wageningen University
  More Information

No publications provided by Wageningen University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Lisette de Groot, (Vera van der Velpen), Wageningen University
ClinicalTrials.gov Identifier: NCT01232751     History of Changes
Other Study ID Numbers: NL 32375.081.10
Study First Received: October 21, 2010
Last Updated: January 9, 2012
Health Authority: Netherlands: Medical Ethics Review Committee (METC)

Keywords provided by Wageningen University:
health
women

ClinicalTrials.gov processed this record on September 22, 2014