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Completed

NCT Number: NCT04115462

A Relation of Morphine-induced Itch and Pain Processing

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).

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Key information

Conditions

Morphine Itch Pathological Conditions, Signs and Symptoms Pruritus Signs and Symptoms Skin Diseases Skin Manifestations Skin and Connective Tissue Diseases

Age range

20 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

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

Aalborg, North Denmark, 9000, Denmark

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Morphine

Drug

A 20 mg tablet of morphine

Placebo oral tablet

Drug

Matching tablet of placebo

Histamine

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)

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

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.

Other names: saline

Primary outcomes

  1. Microvascular reactivity

    Time frame: Before and 70 minutes after morphine/placebo administration

    The evoked cutaneous inflammation (quantified by superficial blood perfusion) will be measured by full-field laser perfusion imaging.

  2. Microvascular reactivity

    Time frame: 10 minutes after every itch inductions

    The evoked cutaneous inflammation (quantified by superficial blood perfusion) will be measured by full-field laser perfusion imaging.

  3. Assessment of itch

    Time frame: 1 minute after every itch inductions

    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'.

  4. Assessment of pain

    Time frame: 1 minute after every itch inductions

    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'.

Secondary outcomes

  1. Cold (CPT) and heat (HPT) pain thesholds

    Time frame: 10 minutes before morphine/placebo administration

    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.

  2. Cold (CPT) and heat (HPT) pain thesholds

    Time frame: 60 minutes after morphine/placebo administration

    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.

  3. Pressure Pain Threshold

    Time frame: 10 minutes before morphine/placebo administration

    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.

  4. Pressure Pain Threshold

    Time frame: 60 minutes after morphine/placebo administration

    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.

Sponsors and collaborators

Lead sponsor

Aalborg University

Other

Registry information

Official study 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)

Important dates

Study start
2020
Primary completion
2020
Study completion
2020
First posted
Oct 4, 2019
Registry last updated
Jul 8, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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