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EUGIS

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  1. EUGIS European Union Garlic Inflammation Study in Humans

  2. Background • No clear indications that ‘garlic’ influences lipid metabolism • Indications from cell and animal studies that ‘garlic’ may influence inflammation parameters • Cardiovascular disease (atherosclerosis) shares common features with inflammation • Current treatment strategies for atherosclerosis also focus on inflammation

  3. Aim Study the effects of garlic on inflammatory biomarkers of atherosclerotic disease and on cancer biomarkers in man • Primary endpoint: changes in C-reactive protein ( CRP) • Secondary endpoints: • Indicators of lipid metabolism • Biochemical markers of inflammation • Bloodpressure / heart rate variability • Biomarkers for anti-carcinogenic effects

  4. Inclusion criteria • Able and willing to give informed consent • 90 subjects of either gender* • Aged between 40-75 years • Smoking≥ 10 cigarettes/day and BMI≥ 24.5 kg/m2 * Power calculation to find a reduction of 30% in plasma CRP levels with = 0.05 and a power of 80% about 30 subjects per group are needed

  5. Exclusion criteria • Any major clinical significant abnormality detected by a general health questionnaire or by blood sampling • Chronic drug treatment /use of medication • Participation in prior study in the last 3 months or blood donation • Inadequate use of contraceptives / pregnancy / lactating women • History of alcohol / drug abuse • Positive test results for HepB/C or HIV • Dislike of garlic

  6. Experimental design • Double dummy placebo-controlled trial • 3 parallel groups (n=30) I.C. / screening Intervention period 4 - 5 11-12 weeks -2 0 Blood and urine collection

  7. 12-weeks treatment • 1. Garlic (from EU-sponsored Printanor 2001) • Lichtwer capsule preparation (300 mg) • 2.1g daily (3 cap - breakfast & 4 cap at dinner) • 2. Atorvastatin: • 40 mg/day daily at dinner • 3. Placebo: • garlic and statin placebo daily

  8. Measurements • Safety: • Parameters of muscle and liver function • Haematology • Clinical: • Blood pressure • 12 lead ECG (HR, conduction) • Heart Rate Variability (HRV)

  9. Measurements • Biochemical: • Cholesterol, HDL, and triglycerides; • CRP, vWF, Fbg, and cytokines after whole blood stimulation without or with LPS (TNF-α, IL-10); • Sensitivity of leukocytes to inflammatory stimulus; • Cancer biomarkers: anti-oxidant enzymes (GPX, SOD), DNA damage (Comet assay), anti-mutagenic properties of urine (Ames test); • Metabolites of garlic compounds in plasma and urine;

  10. Additional measurements suggested in the EU proposal • SAA, and PAI-1 • s-VCAM / s-ICAM / s-Selectine • MCP-1 and other chemokines • Endothelin 1 and 3 • Plasma ox-LDL • Urine isoprostanes

  11. Current study status •  Subjects at information sessions: >148 •  Subjects signing IC: 142 •  Subjects randomised : 92 •  Subjects completed: 84 •  Subjects withdrawn: 8 (6 non-related AEs) • Entire clinical study period: < 5 months! • last samples at Jan 15th

  12. Study population - baseline • Female • n = 47 • age: 40-67 yrs • BMI: 29.6 (SD: 4.1) kg/m2 • BP: 124 (18) / 76 (12) mm Hg • Male • n = 37 • age: 40-63 yrs • BMI: 29.3 (SD: 3.2) kg/m2 • BP: 130 (11) / 82 (10) mm Hg

  13. Baseline lipids • Female • Total Cholesterol: 5.60 (1.01) mmol/L (3.9-7.3) • HDL-Cholesterol: 1.35 (0.32) mmol/L (>1.16) • LDL-Cholesterol: 3.52 (0.95) mmol/L • Triglycerides: 1.63 (0.95) mmol/L(0.8-1.94) • Male • Total Cholesterol: 5.71 (1.04) mmol/L (3.9-7.3) • HDL-Cholesterol: 1.11 (0.32) mmol/L (>0.90) • LDL-Cholesterol: 3.54 (0.99) mmol/L • Triglycerides: 2.35 (1.32) mmol/L(0.8-1.94)

  14. Adverse Events • AE’s • Headache: • 52 episodes in 41 subjects • Abdominal discomfort • 36 episodes in 26 subjects • Other • 60 various events (URT infection, ‘pains’, intercurrents)

  15. PLAN • All samples have been / are being shipped • Unblinding next week • Primary parameter laboratory analysis completed at Jan 31st • Stats analysis time allocated • Main report around March 1st 2004 • Additional reports: to be discussed

  16. THANKS • Lichtwer • S Striegl • T Haffner • LUMC pharmacy • R Press • TNO-PG • P Meijer • R Kret • R Streunding • CHDR • M van Doorn • I Kamerling • Nursing staff • Participants who tolerated 2.1 gram garlic/day