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

NCT02463383 | Completed Early Phase 1

• 1 other identifier: M215
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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.

Conditions

Breast Cancer

Keywords

PPAR-gamma; estrogens; NSAIDS; polymorphism; metabolomics

Outcome Measures

Primary Outcomes (1)

• Serum estrone sulphate (pmol/l)

  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 Outcomes (5)

• Serum estrone (pmol/l)

  from 40 min before to 90 min after alcohol consumption

• Serum SHBG (nmol/l)

  from 40 min before to 90 min after alcohol consumption

• Serum ethanol (g/l)

  from 40 min before to 90 min after alcohol consumption

• Serum metabolomics (relative metabolite intensity)

  from 40 min before to 24h after alcohol intake

• Urine metabolomics (relative metabolite intensity)

  from 40 min before to 24h after alcohol intake

Study Arms (2)

Sequence 1

EXPERIMENTAL

1. Ibuprofen Tab 400MG 2. Placebo Tab

Drug: Ibuprofen Tab 400 MG; Drug: Placebo tab

Sequence 2

EXPERIMENTAL

1. Placebo tab 2. Ibuprofen Tab 400MG

Drug: Ibuprofen Tab 400 MG; Drug: Placebo tab

Interventions

Ibuprofen Tab 400 MG DRUG

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

Also known as: (RS)-2-(4-(2-methylpropyl)phenyl)propanoic acid

Sequence 1; Sequence 2

Placebo tab DRUG

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

Also known as: placebo tablet

Sequence 1; Sequence 2

Eligibility Criteria

• Age: 50 Years - 70 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• a history of alcohol abuse
• alcohol abstaining
• 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);
• major health problems, such as ulcers, heart diseases, diabetes or cancer
• previous or current use of HRT
• 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);
• being allergic to alcohol and/or Ibuprofen
• smoking

Sponsors & Collaborators

• Professor Lars Ove Dragsted: lead
• Technical University of Denmark: collaborator

Study Sites (1)

Department of Nutrition, Exercise and Sports, University of Copenhagen

Frederiksberg, 1958, Denmark

Location

Related Publications (1)

• 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.

  PMID: 27102200 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Ibuprofen

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Phenylpropionates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals

Study Officials

• Lars O Dragsted, PhD

  University of Copenhagen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, Head of Section

Model Details: Participants are randomized to an ibuprofen or placebo pill in the first period and are then provided with placebo or ibuprofen pills, respectively, in the second period in a crossover fashion. Alcohol (0.4g/kg bw) is provided as a challenge 30min after the pill has been swallowed.

Study Record Dates

• First Submitted: May 17, 2015
• First Posted: June 4, 2015
• Study Start: September 1, 2013
• Primary Completion: October 1, 2014
• Study Completion: December 1, 2015
• Last Updated: December 12, 2017

Record last verified: 2017-12

Locations

DK (1)