Paracetamol and Pharmacogenetic

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: Paracetamol (drug)

• Registration Number: NCT01520792
• Lead Sponsor: University Hospital, Clermont-Ferrand

Brief Summary

Recent works has emphasized that the mechanism of action of paracetamol analgesic depend on its metabolism in the body, since a breakdown product of paracetamol, the AM404 is now considered the analgesic metabolite of paracetamol suggesting as paracetamol may be a pro-drug.

Indeed, it has been shown that paracetamol may have a deleterious effect, especially in vulnerable populations (hepatic insufficiency, elderly). First results showed a very significant decrease in sulfatation and gluthatione and increased phase 1 metabolism of acetaminophen, which involves enzymes such as cytochrome P450.

Multifactorial causes, combining nutrition (depletion of sulfur amino acids), increased detoxification of toxic metabolites of paracetamol, stress or trauma are discussed to explain the results.

Clinical studies showed a great variability of pain assessment by patients and variability in the metabolic response of paracetamol. Genetic factors probably play a role remains largely unknown.

The review of the literature on genetic polymorphism shows the involvement of a number of enzymes that are well known, predominantly on the metabolism of acetaminophen liver, but without connection with its analgesic effect. This is a critical missing link in the understanding of the analgesic effect of paracetamol.

Detailed Description

Randomized, single-center, placebo-controlled, double-blind, cross-over in 100 healthy volunteers meeting the inclusion criteria and receiving 2g of paracetamol orally or placebo on two study periods separated by one week.

The evaluation criterion is the difference in areas under the curve of pain thresholds to thermal and mechanical stimulations test

Study Timeline

• Study First Submitted: 2011-08-30
• Study Start: 2011-11
• Study First Submitted QC: 2012-01-26
• Study First Posted: 2012-01-30
• Status Verified: 2013-05
• Primary Completion: 2013-05
• Study Completion: 2013-05
• Last Update Submitted: 2013-05-13
• Last Update Posted: 2013-05-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 100

Inclusion Criteria

• Healthy volunteers
• Males
• Aged between 18 and 30 years

Exclusion Criteria

• Subject without cons-indications of paracetamol

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Paracetamol	Paracetamol (drug)	-

Primary Outcome Measures

Name	Time	Method
Correlation between Pharmacogenetic profile and pain threshold	until 14 days before the administration

Secondary Outcome Measures

Name	Time	Method
Measures of thermal and mechanical pain thresholds	until 1 hour before the administration
Determination of blood concentration of gluthatione	until 1 hour before administration

Trial Locations

Locations (1)

CHU Clermont-Ferrand; 🇫🇷 Clermont-Ferrand, France