The Central Analgesic Effects of Paracetamol on Serotonergic Pathways

Analgesia Clinical Trial

Official title:

The Central Analgesic Effects of Paracetamol on Serotonergic Pathways

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00970450
• Other study ID #: DAAnaBaselParacetamol 2
• Status: Completed
• Phase: N/A
• First received: August 20, 2009
• Last updated: January 28, 2013
• Start date: November 2009
• Est. completion date: April 2010

Study information

• Verified date: January 2013
• Source: University Hospital, Basel, Switzerland
• Contact: n/a
• Is FDA regulated: No
• Health authority: Switzerland: Swissmedic
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: April 2010
• Est. primary completion date: March 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 20 Years to 35 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Analgesia

Intervention

Drug:
• Paracetamol
Paracetamol 1 g i.v. once
• Tropisetron
Tropisetron 5 mg i.v. once
• Placebo
Saline

Locations

Country	Name	City	State
Switzerland	University Hospital of Basel	Basel

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Basel, Switzerland

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pain		all 20 minutes up to 180 minutes after starting the experiment	No