Patients will be treated with aspirin 100 mg/day for one year

Patients will be treated with placebo for one year

Diabetes

Patients suffering from type 2 diabetes will be randomized to receive 100 mg/day or placebo for one year

Aspirin

Patients in this arm will be treated with placebo

Placebo

Internal and Medical Specialities Department - Policlinico Umberto I

Aspirin and Renal Disease Progression in Patients With Type 2 Diabetes

Effect of Aspirin on Renal Disease Progression in Patients With Type 2 Diabetes: a Multicentre Double-blind, Placebo-controlled, Randomised Trial. The LEDA (renaL disEase Progression by Aspirin in Diabetic pAtients) Study.

The aim of our study is to evaluate the decline in renal function in diabetic patients treated with low-dose aspirin (100 mg/day) vs. untreated diabetic patients. In particular, we will evaluate:
The absolute change in eGFR, calculated as the difference between eGFR at 12 months - baseline eGFR;
The rapid decline in renal function, defined as a reduction of eGFR ≥5 ml/min at 1 years.
The change of renal function class (from G1 to G2, from G2 to G3a and so on) at 6 and 12 months.

As secondary endpoint, we will evaluate changes in the urinary excretion TxB2 both baseline and at one year. Changing levels of urinary TxB2 will then be related to renal function.

Francesco Violi

Full professor

University of Roma La Sapienza

Oral administration of a single pill of celecoxib (200 mg). Celecoxib pills will be over-encapsulated to match the placebo.

Oral administration of a single placebo pill.

Oral administration of a single pill of celecoxib (200 mg). Celecoxib pills will be over-encapsulated to match the placebo.
Celecoxib: Blood and urine collections before and 3 hours after celecoxib administration.

Celecoxib

Oral administration of a single placebo pill.
Placebo: Blood and urine collections before and 3 hours after placebo administration.

Total

Sex: Female, Male

PGE2 in blood taken from celecoxib-treated subjects and stimulated ex vivo with LPS was compared to similarly treated blood from placebo group. Plasma PGE2 was normalized to sample volume (ng/ml) and expressed as a percentage of subject's pre-dose control using the formula: percentage of pre-dose control = (Cpost-dose/Cpre-dose) × 100%, where C represents PGE2 concentration in ng/ml.

Quantification of Plasma Lipids in the Whole Blood: Prostaglandin E2 (PGE2)

PGF2a in blood taken from celecoxib-treated subjects and stimulated ex vivo with LPS was compared to similarly treated blood from placebo group. Plasma PGF2a was normalized to sample volume (ng/ml) and expressed as a percentage of subject's pre-dose control using the formula: percentage of pre-dose control = (Cpost-dose/Cpre-dose) × 100%, where C represents PGF2a concentration in ng/ml.

Quantification of Plasma Lipids in the Whole Blood: Prostaglandin F2a (PGF2a)

TxB2 in blood taken from celecoxib-treated subjects and stimulated ex vivo with LPS was compared to similarly treated blood from placebo group. Plasma TxB2 was normalized to sample volume (ng/ml) and expressed as a percentage of subject's pre-dose control using the formula: percentage of pre-dose control = (Cpost-dose/Cpre-dose) × 100%, where C represents TxB2 concentration in ng/ml.

Quantification of Plasma Lipids in the Whole Blood: Thromboxane B2 (TxB2)

15-HETE in blood taken from celecoxib-treated subjects and stimulated ex vivo with LPS was compared to similarly treated blood from placebo group. Plasma 15-HETE was normalized to sample volume (ng/ml) and expressed as a percentage of subject's pre-dose control using the formula: percentage of pre-dose control = (Cpost-dose/Cpre-dose) × 100%, where C represents 15-HETE concentration in ng/ml.

Quantification of Plasma Lipids in the Whole Blood: 15-Hydroxyeicosatetraenoic Acid (15-HETE)

Effect of celecoxib on systemic PGE2 was assessed by comparing urine PGE-M in celecoxib vs placebo-treated groups. Urine data are reported as a percentage of the volunteer's own pre-dose control using the formula: percentage of pre-dose control = (Cpost-dose/Cpre-dose) × 100%, where C represents metabolite concentration in ng/mg creatinine.

Urinary Lipid Metabolites: PGE2 Metabolite (PGE-M)

Celecoxib plasma concentration will be measured in drug-treated and placebo groups by UPLC-MS/MS, and will be expressed as amount of the drug per volume of plasma (ng/ml). At Tmax of 3 hours after a single oral dose of celecoxib of 200 mg, drug plasma concentration should correspond to the maximum plasma concentration or Cmax.

Celecoxib Plasma Concentration

Effect of celecoxib on systemic PGI2 was assessed by comparing urine PGI-M in celecoxib vs placebo-treated groups. Urine data are reported as a percentage of the volunteer's own pre-dose control using the formula: percentage of pre-dose control = (Cpost-dose/Cpre-dose) × 100%, where C represents metabolite concentration in ng/mg creatinine.

Urinary Lipid Metabolites: PGI2 Metabolite (PGI-M)

Effect of celecoxib on systemic TxB2 was assessed by comparing urine Tx-M in celecoxib vs placebo-treated groups. Urine data are reported as a percentage of the volunteer's own pre-dose control using the formula: percentage of pre-dose control = (Cpost-dose/Cpre-dose) × 100%, where C represents metabolite concentration in ng/mg creatinine.

Urinary Lipid Metabolites: TxB2 Metabolite (Tx-M)

Overall Study

Garret A. FitzGerald

Healthy

Blood and urine collections before and 3 hours after celecoxib administration.

Blood and urine collections before and 3 hours after placebo administration.

The Clinical Translational Research Center (CTRC) at the Hospital of the University of Pennsylvania

Lipidomics Screening of Celecoxib in ex Vivo Human Whole Blood Assay - Part B

A Randomized, Double-blinded, Placebo-controlled Study Investigating the Pharmacological Response to Celecoxib Using ex Vivo Human Whole-blood Assay (hWBA) and Broad-spectrum Lipidomics Analysis

University of Pennsylvania

Eli Lilly and Company

Thirty (n=30) healthy, non-smoking male and female volunteers between the ages of 18-50 will be included in this study. If all inclusion/exclusion criteria are met, a blood collection of 104 ml will be obtained and the study visit will be completed. If eligible, a volunteer may participate in this study up to four separate times, but not more than two times in the same week.

This is a single blood donation, no drugs or devices administered

Blood draw

Lipidomics Screening of Anti-inflammatory Drugs and Drug Candidates in Vitro - Part A

Broad-spectrum Lipidomics Screening of Anti-inflammatory Drugs and Drug Candidates in In Vitro Human Whole-blood Assay (hWBA)

Evaluation of cardiovascular risk factors, oxidative stress and fatty acid metabolism in a cohort of blood donors

Cardiovascular Disease

AVIS

Vascular Medicine Unit, Department of Medical Science and Biotechnology

Cardiovascular Risk Factors, Lipid Metabolism and Oxidative Stress

Relation Between Fatty Acids and Oxidative Stress Markers With Cardiovascular Risk Factors in a Healthy Population

Assessment of plasma reference values of the complete fatty acid profile, oxysterols and alpha- and gamma-tocopherol in healthy italian subjects

The assessment of the complete fatty acids profile, oxysterols and vitamin E (alpha- and gamma-tocopherol) would reveal associations with components cardiovascular risk factors of the metabolic syndrome

Prospective evaluation of cardiovascular events as function of baseline fatty acids and oxidative stress

arachidonate/infarction

Aspirin and Renal Disease Progression in Patients With Type 2 Diabetes

Lipidomics Screening of Celecoxib in ex Vivo Human Whole Blood Assay - Part B

Lipidomics Screening of Anti-inflammatory Drugs and Drug Candidates in Vitro - Part A

Cardiovascular Risk Factors, Lipid Metabolism and Oxidative Stress

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