Effect of PPARγ2 Polymorphism and NSAIDs on Acute Alcohol-induced Changes in Serum Estrogens Among Post-menopausal Women (EPPNASE)

December 11, 2017 updated by: Professor Lars Ove Dragsted

Alcohol-related Breast Cancer in Postmenopausal Women - Effect of PPARG2pro12ala Polymorphism on Female Sex-hormone Levels and Interaction With Alcohol Consumption and NSAID Usage

Postmenopausal women, stratified by a peroxisome proliferator-activated receptor gamma-2 (PPARG) polymorphism, were given the following treatments in a random order with a 5w wash-out period: a 400mg ibuprofen tablet or a placebo tablet; both treatments were followed after 30min by a single acute dose of 0.4g alcohol per kg bw. Serum estrogen levels were measured before and at three timepoints after alcohol intake. It is hypothesized that the acute decrease in estrogen sulphate and other markers of estrogens after alcohol intake is modulated by ibuprofen and by PPARG genotype.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

In a pilot human intervention trial we aimed to determine the effect of the PPARG Pro12Ala polymorphism and the PPARγ stimulator, Ibuprofen, on sex-hormone levels following alcohol intake in postmenopausal women. Seven women with PPARG Pro12Ala and 18 PPARG wildtype women were included.The study was performed as a randomised, double-blinded, placebo controlled 2x24 h crossover study. The volunteers were randomised to 1 of 2 groups who got the two treatments in different orders. Treatment 1 was a placebo tablet with water followed after 30min by an alcoholic drink providing 0,4g alcohol per kilogram bw and treatment 2 was an Ibuprofen tablet (400mg) with water followed by the same alcoholic drink. The two treatments were separated by a 5-7 weeks washout period. Alcohol was supplied as 7.7% ethanol in a lime-flavoured drink and was consumed over 15 min. EDTA-plasma was collected 40min before and 30, 60 and 90 min after ethanol intake as well as after 24 hours. Ibuprofen (400mg) was provided together with 100mL water 30min before the ethanol. Urine was collected throughout the 24 hour interval. Serum estrone, estrone sulphate, serum estrogen-binding globulin (SHBG), and ethanol were determined. It is hypothesized that the acute decrease in estrogen sulphate and other markers of estrogens after alcohol intake is modulated by ibuprofen and by PPARG genotype.

Study Type

Interventional

Enrollment (Actual)

25

Phase

  • Early Phase 1

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

  • Denmark
      • Frederiksberg, Denmark, 1958
        • Department of Nutrition, Exercise and sports, University of Copenhagen

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

50 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  1. postmenopausal (last menses at least 1 year earlier);
  2. having a weekly alcohol use of less than 14 drinks
  3. having a BMI of 18-35;

Exclusion Criteria:

  1. a history of alcohol abuse
  2. alcohol abstaining
  3. history of hysterectomy before last menses with preservation of both ovaries (unless a medical confirmation for the postmenopausal status exists or the participant is 60 years or older);
  4. major health problems, such as ulcers, heart diseases, diabetes or cancer
  5. previous or current use of HRT
  6. taking prescription medications that could interfere with the study (i.e. daily use of NSAIDs and/or medication that interact with PPARγ e.g. cholesterol lowering medicine);
  7. being allergic to alcohol and/or Ibuprofen
  8. smoking

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

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Sequence 1
  1. Ibuprofen Tab 400MG
  2. Placebo Tab
Drug: Ibuprofen Tab 400 MG
400mg ibuprofen is provided and an alcohol challenge (0.4g/kg bw) is given 30min later
Other Names:
  • (RS)-2-(4-(2-methylpropyl)phenyl)propanoic acid
Drug: Placebo tab
A placebo tablet is provided and an alcohol challenge (0.4g/kg bw) is given 30min later
Other Names:
  • placebo tablet
Experimental: Sequence 2
  1. Placebo tab
  2. Ibuprofen Tab 400MG
Drug: Ibuprofen Tab 400 MG
400mg ibuprofen is provided and an alcohol challenge (0.4g/kg bw) is given 30min later
Other Names:
  • (RS)-2-(4-(2-methylpropyl)phenyl)propanoic acid
Drug: Placebo tab
A placebo tablet is provided and an alcohol challenge (0.4g/kg bw) is given 30min later
Other Names:
  • placebo tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Serum estrone sulphate (pmol/l)
Time Frame: from 40 min before to 90 min after alcohol consumption
Plasma estrone sulfate concentration after acute ethanol intake by Ibuprofen intake and/or PPARG genotype
from 40 min before to 90 min after alcohol consumption

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Serum estrone (pmol/l)
Time Frame: from 40 min before to 90 min after alcohol consumption
Plasma estrone decrease after acute ethanol intake by ibuprofen intake and/or PPARG genotype
from 40 min before to 90 min after alcohol consumption
Serum SHBG (nmol/l)
Time Frame: from 40 min before to 90 min after alcohol consumption
Plasma SHBG concentration after acute ethanol ingestion by ibuprofen intake and/or PPARG genotype
from 40 min before to 90 min after alcohol consumption
Serum ethanol (g/l)
Time Frame: from 40 min before to 90 min after alcohol consumption
Plasma ethanol concentration after acute ethanol ingestion
from 40 min before to 90 min after alcohol consumption
Serum metabolomics (relative metabolite intensity)
Time Frame: from 40 min before to 24h after alcohol intake
The plasma metabolome profile by time after alcohol intake
from 40 min before to 24h after alcohol intake
Urine metabolomics (relative metabolite intensity)
Time Frame: from 40 min before to 24h after alcohol intake
The urine metabolome profile by time after alcohol intake
from 40 min before to 24h after alcohol intake

Collaborators and Investigators

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

Sponsor

Professor Lars Ove Dragsted

Collaborators

Technical University of Denmark

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

September 1, 2013

Primary Completion (Actual)

October 1, 2014

Study Completion (Actual)

December 1, 2015

Study Registration Dates

First Submitted

May 17, 2015

First Submitted That Met QC Criteria

June 3, 2015

First Posted (Estimate)

June 4, 2015

Study Record Updates

Last Update Posted (Actual)

December 12, 2017

Last Update Submitted That Met QC Criteria

December 11, 2017

Last Verified

December 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • M215

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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