The Central Analgesic Effects of Paracetamol on Serotonergic Pathways

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier:
NCT00970450
First received: August 20, 2009
Last updated: January 28, 2013
Last verified: January 2013
  Purpose
  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 Intervention
Analgesia
Drug: Paracetamol
Drug: Tropisetron
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Basic Science
Official Title: The Central Analgesic Effects of Paracetamol on Serotonergic Pathways

Resource links provided by NLM:


Further study details as provided by University Hospital, Basel, Switzerland:

Primary Outcome Measures:
  • Pain [ Time Frame: all 20 minutes up to 180 minutes after starting the experiment ] [ Designated as safety issue: No ]

Enrollment: 16
Study Start Date: November 2009
Study Completion Date: April 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Saline
Active Comparator: Tropisetron
Proband will receive Tropisetron alone
Drug: Tropisetron
Tropisetron 5 mg i.v. once

  Eligibility

Ages Eligible for Study:   20 Years to 35 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00970450

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

No publications provided

Responsible Party: University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier: NCT00970450     History of Changes
Other Study ID Numbers: DAAnaBaselParacetamol 2
Study First Received: August 20, 2009
Last Updated: January 28, 2013
Health Authority: Switzerland: Swissmedic

Keywords provided by University Hospital, Basel, Switzerland:
Paracetamol
Tropisetron
Central analgesic effect
Area of allodynia
Secondary hyperalgesia

Additional relevant MeSH terms:
Acetaminophen
Analgesics
Tropisetron
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Antipyretics
Antiemetics
Autonomic Agents
Gastrointestinal Agents
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014