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The Central Analgesic Effects of Paracetamol on Serotonergic Pathways

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: NCT00970450
Recruitment Status : Completed
First Posted : September 2, 2009
Last Update Posted : January 29, 2013
Information provided by (Responsible Party):
University Hospital, Basel, Switzerland

Brief Summary:
  1. Introduction

    Paracetamol, an analgesic prescribed daily, has been in use for more than 50 years. Surprisingly, its mode of action is still unclear. One postulated mechanism is the reinforcement of descending inhibitory pathways. A recent publication in a human pain model raises the question of whether or not Paracetamol acts according to a central serotonergic mechanism. Unfortunately, the chosen model was unable to differentiate between overall pain, secondary hyperalgesia and allodynia. In particular, secondary hyperalgesia and allodynia are central effects.

    The planned study will examine the central analgesic effects of paracetamol on allodynia and hyperalgesia by blocking the central effect by adding tropisetron. It will be based on an internationally accepted model for the initiation of secondary hyperalgesia, which was developed and tested by colleagues in Erlangen.

  2. Study work plan

    This prospective, randomized, placebo-controlled, double-blinded, cross-over trial in 16 male volunteers will address pain ratings and the area of secondary hyperalgesia/allodynia in a human model of electrically evoked pain and compare four different treatment scenarios:

    • Paracetamol 1 g;
    • Paracetamol, 1 g and Tropisetron 5 mg;
    • Tropisetron, 5 mg; and
    • Saline.

    Each volunteer will be allocated to each scenario in a cross-over fashion. Four separate treatment trials, at least two weeks apart, will be performed. Each volunteer will be familiarized with the stimulation procedure prior to participation.

  3. Ethical considerations

    Informed consent will be obtained from each volunteer. In addition, each volunteer will receive remuneration after participating in the study.

    Paracetamol is considered to be a very safe drug in healthy patients. Tropisetron, another safe medication, is routinely used in anaesthetic practice as an antiemetic drug. Headache, flush and liver parameter elevation are very rare side effects of minor importance in our daily clinical work as anaesthetists.

    This pain provoking procedure was developed at the University Erlangen Germany. It is a standardized method and has repeatedly received approval by research ethics committees internationally. Furthermore, the investigators applied this model to a recent study in Basel (cf your decision "study protocol 330/07;" unpublished data, analysis and writing in progress).

  4. Patient number and timetable

    The investigators will examine 16 volunteers and expect the experimental component to last 3 months. The investigators plan to complete this study within one year.

  5. Study importance

The mode of action of paracetamol remains unclear. The investigators think that this study will enable them to answer important questions concerning the action of paracetamol. The investigators hope that further understanding of this regularly prescribed drug will help us to better understand the complex mechanisms of pain.

Condition or disease Intervention/treatment Phase
Analgesia Drug: Paracetamol Drug: Tropisetron Drug: Placebo Not Applicable

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 16 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Basic Science
Official Title: The Central Analgesic Effects of Paracetamol on Serotonergic Pathways
Study Start Date : November 2009
Actual Primary Completion Date : March 2010
Actual Study Completion Date : April 2010

Arm Intervention/treatment
Experimental: Paracetamol Drug: Paracetamol
Paracetamol 1 g i.v. once

Experimental: Paracetamol/Tropisetron Drug: Paracetamol
Paracetamol 1 g i.v. once

Drug: Tropisetron
Tropisetron 5 mg i.v. once

Placebo Comparator: Saline
Proband will receive Saline
Drug: Placebo

Active Comparator: Tropisetron
Proband will receive Tropisetron alone
Drug: Tropisetron
Tropisetron 5 mg i.v. once

Primary Outcome Measures :
  1. Pain [ Time Frame: all 20 minutes up to 180 minutes after starting the experiment ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   20 Years to 35 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  • Healthy male volunteers
  • 20-35 years of age
  • No known medical disorders
  • BMI 18.5 - 39.9 (kg/m2)

Exclusion Criteria:

  • Known drug allergies (paracetamol, tropisetron)
  • Excessive consumption of tobacco (more than 10 cigarettes a day)
  • Excessive consumption of tea or coffee (more than 5 cups a day)
  • Recreational drug addiction
  • Consumption of any medication on the trial days

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): NCT00970450

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University Hospital of Basel
Basel, Switzerland, 4031
Sponsors and Collaborators
University Hospital, Basel, Switzerland
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Principal Investigator: Wilhelm Ruppen, MD University Hospital, Basel, Switzerland

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Responsible Party: University Hospital, Basel, Switzerland Identifier: NCT00970450    
Other Study ID Numbers: DAAnaBaselParacetamol 2
First Posted: September 2, 2009    Key Record Dates
Last Update Posted: January 29, 2013
Last Verified: January 2013
Keywords provided by University Hospital, Basel, Switzerland:
Central analgesic effect
Area of allodynia
Secondary hyperalgesia
Additional relevant MeSH terms:
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Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Analgesics, Non-Narcotic
Autonomic Agents
Gastrointestinal Agents
Serotonin 5-HT3 Receptor Antagonists
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action