Cognitive Impact of Paracetamol in Healthy Volunteers (ICP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01390467
Recruitment Status : Completed
First Posted : July 11, 2011
Last Update Posted : January 30, 2012
Grünenthal GmbH
Information provided by (Responsible Party):
University Hospital, Clermont-Ferrand

Brief Summary:
Randomized study, double-blind, crossover, controlled versus placebo.

Condition or disease Intervention/treatment Phase
Healthy Drug: Cantab® Phase 1

Detailed Description:

Paracetamol impact on cognitive processes has been until recently little studied in literature that presents conflicting results. Some authors do not describe any cognitive performance change (Bradley and Nicholson, 1987) but more recent studies (Ishida et al., 2007) report an interesting performance improvement in therapeutic doses of paracetamol.

This improved performance would use the serotonergic pathway that is involved in the analgesic mechanism of paracetamol as the investigators demonstrated in our laboratory on previous work (Pickering et al. 2006, 2008). However, non-therapeutic dose, instead, showed a deterioration of memory processes in animals which may be link to implication of Cyclooxygenases COX-2. Indeed, several studies have demonstrated (Sharifzadeh et al. 2005; Teather et al., 2005) that anti COX-2 (such as Celebrex) cause in animal a deleterious effect on memory, while an anti COX1 and 2 (as indomethacin) or an anti COX1 (as piroxicam) lead to no change. A dose-effect relationship is therefore suggested on animals. Furthermore, a recent study in healthy volunteers showed that paracetamol acts not only on pain but also on pain / stress in society in everyday life (" social pain ") (deWall et al., 2010). By fMRI, these psychologists have shown that the reduction of "social" pain is associated with a decrease in neuronal activity in brain regions that are involved in social processes but also those who are involved in pain processes (anterior cingulate cortex , anterior insula etc..). They also showed that paracetamol known for its painkillers properties may reduce the painful feelings of rejection or shelved in everyday life. The cognitive-emotional impact of paracetamol is even more interesting that the investigators now know that its metabolism could involve cannabinoids receptors, particularly CB1 in hippocampus and association cortex involved themselves in cognitive phenomena.

INSERM U766 team to which the investigators belong has proposed the following sequence from preclinical : 1) metabolism of acetaminophen in analgesic metabolite AM404 via FAAH enzyme, 2) AM404 acts indirectly on CB1 receptors, 3) strengthening of bulbo spinal descending pathways by the endocannabinoid system, 4) involvement of serotonergic receptors pain suppressors.

This protocol follows a pilot that the investigators completed (HOP NCT01053650, unpublished results yet) where the investigators studied the impact of 2g of paracetamol in healthy volunteers. The investigators showed a memory improvement, but with no placebo group, it has not been possible to conclude a significant impact of oral paracetamol. Thus, this protocol will allow us to better understand if paracetamol can affect some cognitive processes, particularly vigilance, memory and decision making.

In addition, the investigators will build a biological collection to assess the pharmacogenetic profile of subjects and, in a secondary objective, correlate it to cognitive characteristics of subjects.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 44 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Cognitive Impact of Paracetamol in Healthy Volunteers
Study Start Date : July 2011
Actual Primary Completion Date : July 2011
Actual Study Completion Date : January 2012

Intervention Details:
    Drug: Cantab®
    Randomized study, double-blind, crossover, controlled versus placebo.

Primary Outcome Measures :
  1. Assess cognitive impact of taking paracetamol within healthy volunteers by comparing the results on cognitive tests Cantab® between two passages, in particular a memory test (SOC) [ Time Frame: after the results on cognitive tests Cantab ]

Secondary Outcome Measures :
  1. Assess cognitive impact of taking paracetamol on other cognitive tests Cantab® (understanding : MOT and DMS, reaction time : RTI, visual memory : PRM, decision making : IST) [ Time Frame: after an other cognitive test Cantab ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 25 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  • healthy volunteers,
  • aged over 18 years and not more than 25 years,
  • males,
  • free from any treatment in the 7 days preceding inclusion especially no use of analgesics or anti-inflammatories

Exclusion Criteria:

  • Contraindications to the administration of paracetamol
  • medical and/or surgical history judged by the investigator or his representative as being incompatible with the test, especially subjects with neuropathic pain
  • evolutionary pathology at review for inclusion
  • excessive intake of alcohol, tobacco (more than 10 cigarettes / day), coffee, tea or drinks containing caffeine (equivalent to more than 4 cups per day) or drug

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01390467

Sponsors and Collaborators
University Hospital, Clermont-Ferrand
Grünenthal GmbH
Principal Investigator: Gisèle PICKERING University Hospital, Clermont-Ferrand

Responsible Party: University Hospital, Clermont-Ferrand Identifier: NCT01390467     History of Changes
Other Study ID Numbers: CHU-0095
2011-000662-35 ( EudraCT Number )
First Posted: July 11, 2011    Key Record Dates
Last Update Posted: January 30, 2012
Last Verified: January 2012

Keywords provided by University Hospital, Clermont-Ferrand:
Cognitive impact

Additional relevant MeSH terms:
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs