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

NCT ID: NCT02463383

Last Updated: 2017-12-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-09-30
• Study Completion Date: 2015-12-31

Brief Summary

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.

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.

Conditions

Breast Cancer

Keywords

PPAR-gamma; estrogens; NSAIDS; polymorphism; metabolomics

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

Sequence 1

1. Ibuprofen Tab 400MG

2. Placebo Tab

Group Type: EXPERIMENTAL

Ibuprofen Tab 400 MG

Intervention Type: DRUG

400mg ibuprofen is provided and an alcohol challenge (0.4g/kg bw) is given 30min later

Placebo tab

Intervention Type: DRUG

A placebo tablet is provided and an alcohol challenge (0.4g/kg bw) is given 30min later

Sequence 2

1. Placebo tab

2. Ibuprofen Tab 400MG

Group Type: EXPERIMENTAL

Ibuprofen Tab 400 MG

Intervention Type: DRUG

400mg ibuprofen is provided and an alcohol challenge (0.4g/kg bw) is given 30min later

Placebo tab

Intervention Type: DRUG

A placebo tablet is provided and an alcohol challenge (0.4g/kg bw) is given 30min later

Interventions

Ibuprofen Tab 400 MG

400mg ibuprofen is provided and an alcohol challenge (0.4g/kg bw) is given 30min later

Intervention Type: DRUG

Placebo tab

A placebo tablet is provided and an alcohol challenge (0.4g/kg bw) is given 30min later

Intervention Type: DRUG

Other Intervention Names

(RS)-2-(4-(2-methylpropyl)phenyl)propanoic acid; placebo tablet

Eligibility Criteria

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

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Technical University of Denmark

OTHER

Sponsor Role: collaborator

Professor Lars Ove Dragsted

OTHER

Sponsor Role: lead

Responsible Party

Professor Lars Ove Dragsted

Professor, Head of Section

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Lars O Dragsted, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Copenhagen

Locations

Department of Nutrition, Exercise and Sports, University of Copenhagen

Frederiksberg, , Denmark

Countries

Denmark

References

Kopp TI, Jensen DM, Ravn-Haren G, Cohen A, Sommer HM, Dragsted LO, Tjonneland A, Hougaard DM, Vogel U. Alcohol-related breast cancer in postmenopausal women - effect of CYP19A1, PPARG and PPARGC1A polymorphisms on female sex-hormone levels and interaction with alcohol consumption and NSAID usage in a nested case-control study and a randomised controlled trial. BMC Cancer. 2016 Apr 21;16:283. doi: 10.1186/s12885-016-2317-y.

Reference Type: DERIVED

PMID: 27102200 (View on PubMed)

Other Identifiers

M215

Identifier Type: -

Identifier Source: org_study_id