A Relation of Morphine-induced Itch and Pain Processing

NCT ID: NCT04115462

Last Updated: 2020-07-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-15
• Study Completion Date: 2020-07-07

Brief 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).

Detailed 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.

Conditions

Morphine; Itch

Study Design

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

Study Groups

Morphine

Each participant will receive a single dose of 20 mg morphine tablet. At estimated peak-plasma concentration testing is conducted. The subject and the assessor are both blinded to the drug administrations.

Group Type: ACTIVE_COMPARATOR

Morphine

Intervention Type: DRUG

A 20 mg tablet of morphine

Histamine

Intervention Type: DRUG

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)

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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)

Intervention Type: DRUG

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

Placebo

Each participant will receive a single dose of an identical placebo tablet. At estimated peak-plasma concentration testing is conducted. The subject and the assessor are both blinded to the drug administrations.

Group Type: PLACEBO_COMPARATOR

Placebo oral tablet

Intervention Type: DRUG

Matching tablet of placebo

Histamine

Intervention Type: DRUG

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)

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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)

Intervention Type: DRUG

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

Interventions

Morphine

A 20 mg tablet of morphine

Intervention Type: DRUG

Placebo oral tablet

Matching tablet of placebo

Intervention Type: DRUG

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.

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

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

Intervention Type: DRUG

Other Intervention Names

saline

Eligibility Criteria

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

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Aalborg University

OTHER

Sponsor Role: lead

Responsible Party

Silvia Lo Vecchio

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Mech-Sense, Medicinsk Gastroenterologisk ambulatorium, Medicineshus, Aalborg Universitetshospitalet,

Aalborg, North Denmark, Denmark

Countries

Denmark

Other Identifiers

N-20190049

Identifier Type: -

Identifier Source: org_study_id