Effect of PPARγ2 Polymorphism and NSAIDs on Acute Alcohol-induced Changes in Serum Estrogens Among Post-menopausal Women
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Study type: Interventional
Phase: Early Phase 1

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.
    

Intervention name(s): Ibuprofen Tab 400 MG; Placebo tab
Intervention type(s): Drug; Drug
Intervention description(s): 400mg ibuprofen is provided and an alcohol challenge (0.4g/kg bw) is given 30min later; A placebo tablet is provided and an alcohol challenge (0.4g/kg bw) is given 30min later
Other intervention name(s): (RS)-2-(4-(2-methylpropyl)phenyl)propanoic acid; placebo tablet
Intervention MeSH terms: Ibuprofen
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: 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.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: PPAR-gamma; estrogens; NSAIDS; polymorphism; metabolomics