A Relation of Morphine-induced Itch and Pain Processing

Itch Clinical Trial

Official title:

A Mechanistic Study on Morphine-induced Orthogonal Neural Plasticity for Itch and Pain Processing in Humans (a Relation of Morphine-induced Itch and Pain Processing)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04115462
• Other study ID #: N-20190049
• Status: Completed
• Phase: N/A
• Start date: January 15, 2020
• Est. completion date: July 7, 2020

Study information

• Verified date: July 2020
• Source: Aalborg University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

In This experiment, the investigators would like to test the two following hypotheses regarding the mechanisms by which opioids cause itch:

1. Opioids cause itch by a spinal disinhibition mechanism (central nervous system (CNS) effect).

2. Opioids cause itch through a mast cell-destabilizing effect leading to release of histamine and tryptase in the skin where itch is evoked (peripheral mechanism).

Description:

Intrathecal and orally administered opioids are heavily used for the treatment of several acute pain conditions. However, while opioids are effective analgesics for acute pain, they are well-known to frequently cause itch (pruritus) as a side effect according with the two hypotheses stated above. So far, these two hypotheses have never been tested in humans.The present study describes a proposed study design for the purpose of confirming these two hypotheses in parallel in human subjects.

Primary endpoints of the study:

To evaluate changes itch and pain perception, and superficial perfusion after each itch provocations.

Secondary endpoints of the study:

To evaluate the existence of a correlation between itch sensitization and analgesic efficacy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: July 7, 2020
• Est. primary completion date: May 1, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 20 Years to 65 Years

Eligibility

Inclusion Criteria:

• Healthy men and women in the age of 20-65 years

• The participants must be able to speak and understand English

Exclusion Criteria:

• Participants with any clinically significant abnormalities that in the opinion of the investigator may increase the risk associated with trial participation or may interfere with the interpretation of the trial results.

• Pregnant or lactating female persons

• Drug addiction defined as the use of cannabis, opioids or other drugs

• Previous or present neurologic, musculoskeletal or mental illnesses

• Current pain and itch causing diseases or psychiatric disorders

• Participants unable to understand or follow the instructions

• Participating in another study where investigational drug is used

• Participants had known allergy/discomfort to morphine

• Lack of ability to cooperate

Related Conditions & MeSH terms

• Itch
• Morphine

Intervention

Drug:
• Morphine
A 20 mg tablet of morphine
• Placebo oral tablet
Matching tablet of placebo
• Histamine
Histaminergic itch will be evoked by a 1% histamine solution. A droplet of histamine solution will be placed on the predetermined area on the forearm, and the SPT lancet will be pierced through the histamine with 120 g of pressure for 1-2 seconds.
• Cowhage (Mucuna Pruriens)
25 spicules will be inserted in the centre of the predefined skin area on the forearm. The spicules will be gently rubbed for 15-20 seconds in circular motion to facilitate epidermal penetration
• isotonic saline
A droplet of saline (0.9%) as vehicle control will be placed on the predetermined area on the forearm and the lancet will be pierced through the droplet.
• Histamine
Histaminergic itch will be evoked by a 1% histamine solution. A droplet of histamine solution will be placed on the predetermined area on the mandibular area, and the SPT lancet will be pierced through the histamine with 120 g of pressure for 1-2 seconds.
• Cowhage (Mucuna Pruriens)
25 spicules will be inserted in the centre of the predefined skin area on the mandibular area. The spicules will be gently rubbed for 15-20 seconds in circular motion to facilitate epidermal penetration

Locations

Country	Name	City	State
Denmark	Mech-Sense, Medicinsk Gastroenterologisk ambulatorium, Medicineshus, Aalborg Universitetshospitalet,	AAlborg	Nordjylland

Sponsors (1)

Lead Sponsor	Collaborator
Aalborg University

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Microvascular reactivity	The evoked cutaneous inflammation (quantified by superficial blood perfusion) will be measured by full-field laser perfusion imaging.	Before and 70 minutes after morphine/placebo administration
Primary	Microvascular reactivity	The evoked cutaneous inflammation (quantified by superficial blood perfusion) will be measured by full-field laser perfusion imaging.	10 minutes after every itch inductions
Primary	Assessment of itch	Immediately following the itch provocations, participants will be instructed to rate the itch intensity for 10 minutes using a digital visual analogue scale (VAS; eVAS Software: Aalborg, University, Denmark), on a tablet. The scale will be measured from 0 to 100, where 0 represents 'no itch' and 100 'worst itch imaginable'.	1 minute after every itch inductions
Primary	Assessment of pain	Immediately following the itch provocations, participants will be instructed to rate the pain intensity for 10 minutes using a digital visual analogue scale (VAS; eVAS Software: Aalborg, University, Denmark), on a tablet. The scale will be measured from 0 to 100, where 0 represents 'no pain' and 100 'worst pain imaginable'.	1 minute after every itch inductions
Secondary	Cold (CPT) and heat (HPT) pain thesholds	Thermal cold and heat stimuli will be applied by a contact heat-evoked potential stimulator (PATHWAYS; Medoc Ltd, Ramat Yishai, Israel), placed 5 cm distal to the elbow on the right dorsal forearm.	10 minutes before morphine/placebo administration
Secondary	Cold (CPT) and heat (HPT) pain thesholds	Thermal cold and heat stimuli will be applied by a contact heat-evoked potential stimulator (PATHWAYS; Medoc Ltd, Ramat Yishai, Israel), placed 5 cm distal to the elbow on the right dorsal forearm.	60 minutes after morphine/placebo administration
Secondary	Pressure Pain Threshold	Pressure will be applied to the supinator muscle on the left forearm, 15 cm distal to the elbow by a handheld electronic pressure algometer (Somedic AB, Stockholm, Sweden) with a standard probe of 1 cm2.	10 minutes before morphine/placebo administration
Secondary	Pressure Pain Threshold	Pressure will be applied to the supinator muscle on the left forearm, 15 cm distal to the elbow by a handheld electronic pressure algometer (Somedic AB, Stockholm, Sweden) with a standard probe of 1 cm2.	60 minutes after morphine/placebo administration