Paracetamol and Pharmacogenetic

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University Hospital, Clermont-Ferrand
ClinicalTrials.gov Identifier:
NCT01520792
First received: August 30, 2011
Last updated: May 13, 2013
Last verified: May 2013
  Purpose

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.


Condition Intervention Phase
Healthy
Drug: Paracetamol (drug)
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Paracétamol and Pharmacogenetic in Healthy Volunteers

Resource links provided by NLM:


Further study details as provided by University Hospital, Clermont-Ferrand:

Primary Outcome Measures:
  • Correlation between Pharmacogenetic profile and pain threshold [ Time Frame: until 14 days before the administration ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Measures of thermal and mechanical pain thresholds [ Time Frame: until 1 hour before the administration ] [ Designated as safety issue: Yes ]
  • Determination of blood concentration of gluthatione [ Time Frame: until 1 hour before administration ] [ Designated as safety issue: Yes ]

Enrollment: 100
Study Start Date: November 2011
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Paracetamol Drug: Paracetamol (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.

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

  Eligibility

Ages Eligible for Study:   18 Years to 30 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  • Subject without cons-indications of paracetamol
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01520792

Locations
France
CHU Clermont-Ferrand
Clermont-Ferrand, France, 63003
Sponsors and Collaborators
University Hospital, Clermont-Ferrand
Investigators
Principal Investigator: Gisèle PICKERING University Hospital, Clermont-Ferrand
  More Information

No publications provided

Responsible Party: University Hospital, Clermont-Ferrand
ClinicalTrials.gov Identifier: NCT01520792     History of Changes
Other Study ID Numbers: CHU-0101
Study First Received: August 30, 2011
Last Updated: May 13, 2013
Health Authority: France: Ministry of Health

Keywords provided by University Hospital, Clermont-Ferrand:
pharmacogenetic of paracetamol
Pain threshold

Additional relevant MeSH terms:
Acetaminophen
Antipyretics
Physiological Effects of Drugs
Pharmacologic Actions
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 20, 2014