Paracetamol and Pharmacogenetic

NCT01520792 | Completed Phase 1

• 1 other identifier: CHU-0101
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Keywords

pharmacogenetic of paracetamol; Pain threshold

Outcome Measures

Primary Outcomes (1)

• Correlation between Pharmacogenetic profile and pain threshold

  until 14 days before the administration

Secondary Outcomes (2)

• Measures of thermal and mechanical pain thresholds

  until 1 hour before the administration

• Determination of blood concentration of gluthatione

  until 1 hour before administration

Study Arms (1)

Paracetamol

EXPERIMENTAL

Drug: Paracetamol (drug)

Interventions

Paracetamol (drug) DRUG

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.

Paracetamol

Eligibility Criteria

• Age: 18 Years - 30 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• Subject without cons-indications of paracetamol

Sponsors & Collaborators

• University Hospital, Clermont-Ferrand: lead

Study Sites (1)

CHU Clermont-Ferrand

Clermont-Ferrand, 63003, France

Location

Related Publications (1)

• Pickering G, Creveaux I, Macian N, Pereira B. Paracetamol and Pain Modulation by TRPV1, UGT2B15, SULT1A1 Genotypes: A Randomized Clinical Trial in Healthy Volunteers. Pain Med. 2020 Apr 1;21(4):661-669. doi: 10.1093/pm/pnz037.

  PMID: 30908574 DERIVED

MeSH Terms

Interventions

Acetaminophen; Pharmaceutical Preparations

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines

Study Officials

• Gisèle PICKERING

  University Hospital, Clermont-Ferrand

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2011
• First Posted: January 30, 2012
• Study Start: November 1, 2011
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2013
• Last Updated: May 14, 2013

Record last verified: 2013-05

Locations

FR (1)