Effects of Isoflavones on Gene-expression

Postmenopause Clinical Trial

— ISO  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01232751
• Other study ID #: NL 32375.081.10
• Status: Completed
• Phase: N/A
• First received: October 21, 2010
• Last updated: January 9, 2012
• Start date: August 2010
• Est. completion date: October 2011

Study information

• Verified date: January 2012
• Source: Wageningen University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: Medical Ethics Review Committee (METC)
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: October 2011
• Est. primary completion date: October 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 45 Years to 70 Years

Eligibility

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 Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor)

Related Conditions & MeSH terms

• Postmenopause

Intervention

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)

Locations

Country	Name	City	State
Netherlands	Wageningen University	Wageningen	Gelderland

Sponsors (1)

Lead Sponsor	Collaborator
Wageningen University

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Gene-expression measured by micro-arrays	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	No
Primary	Gene-expression measured by micro-arrays	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	No
Secondary	Isoflavone levels in plasma and spoturine	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	No
Secondary	Isoflavone levels in plasma and spoturine	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	No
Secondary	Isoflavone levels in plasma and spoturine	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	No
Secondary	Isoflavone levels in plasma and spoturine	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	No
Secondary	Isoflavone levels in plasma and spoturine	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	No
Secondary	Isoflavone levels in plasma and spoturine	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	No
Secondary	Confirmation of gene-expression with quantitative real time polymerase chain reaction (QPCR)	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	No
Secondary	Confirmation of gene-expression with quantitative real time polymerase chain reaction (QPCR)	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	No
Secondary	Confirmation of gene-expression with quantitative real time polymerase chain reaction (QPCR)	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	No
Secondary	Confirmation of gene-expression with quantitative real time polymerase chain reaction (QPCR)	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	No
Secondary	Confirmation of gene-expression with quantitative real time polymerase chain reaction (QPCR)	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	No
Secondary	Confirmation of gene-expression with quantitative real time polymerase chain reaction (QPCR)	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	No