The Central Analgesic Effects of Paracetamol on Serotonergic Pathways

NCT ID: NCT00970450

Last Updated: 2013-01-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-11-30
• Study Completion Date: 2010-04-30

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.

Conditions

Analgesia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Paracetamol

Group Type: EXPERIMENTAL

Paracetamol

Intervention Type: DRUG

Paracetamol 1 g i.v. once

Paracetamol/Tropisetron

Group Type: EXPERIMENTAL

Paracetamol

Intervention Type: DRUG

Paracetamol 1 g i.v. once

Tropisetron

Intervention Type: DRUG

Tropisetron 5 mg i.v. once

Saline

Proband will receive Saline

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Saline

Tropisetron

Proband will receive Tropisetron alone

Group Type: ACTIVE_COMPARATOR

Tropisetron

Intervention Type: DRUG

Tropisetron 5 mg i.v. once

Interventions

Paracetamol

Paracetamol 1 g i.v. once

Intervention Type: DRUG

Tropisetron

Tropisetron 5 mg i.v. once

Intervention Type: DRUG

Placebo

Saline

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

University Hospital, Basel, Switzerland

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Wilhelm Ruppen, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Basel, Switzerland

Locations

University Hospital of Basel

Basel, Basel, Switzerland

Countries

Switzerland

Other Identifiers

DAAnaBaselParacetamol 2

Identifier Type: -

Identifier Source: org_study_id