NCT04115462

Brief Summary

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

  1. 1.Opioids cause itch by a spinal disinhibition mechanism (central nervous system (CNS) effect).
  2. 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).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
24

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started Jan 2020

Shorter than P25 for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 30, 2019

Completed
4 days until next milestone

First Posted

Study publicly available on registry

October 4, 2019

Completed
3 months until next milestone

Study Start

First participant enrolled

January 15, 2020

Completed
4 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2020

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

July 7, 2020

Completed
Last Updated

July 8, 2020

Status Verified

July 1, 2020

Enrollment Period

4 months

First QC Date

September 30, 2019

Last Update Submit

July 7, 2020

Conditions

Outcome Measures

Primary Outcomes (4)

  • 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

  • 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

  • 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

  • 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 Outcomes (4)

  • Cold (CPT) and heat (HPT) pain thesholds

    10 minutes before morphine/placebo administration

  • Cold (CPT) and heat (HPT) pain thesholds

    60 minutes after morphine/placebo administration

  • Pressure Pain Threshold

    10 minutes before morphine/placebo administration

  • Pressure Pain Threshold

    60 minutes after morphine/placebo administration

Study Arms (2)

Morphine

ACTIVE COMPARATOR

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.

Drug: MorphineDrug: HistamineDrug: Cowhage (Mucuna Pruriens)Drug: isotonic saline

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo oral tabletDrug: HistamineDrug: Cowhage (Mucuna Pruriens)Drug: isotonic saline

Interventions

A 20 mg tablet of morphine

Morphine

Matching tablet of placebo

Placebo

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.

MorphinePlacebo

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

MorphinePlacebo

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.

Also known as: saline
MorphinePlacebo

Eligibility Criteria

Age20 Years - 65 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Healthy men and women in the age of 20-65 years
  • The participants must be able to speak and understand English

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

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

Aalborg, North Denmark, 9000, Denmark

Location

MeSH Terms

Conditions

Pruritus

Interventions

MorphineHistamineSodium Chloride

Condition Hierarchy (Ancestors)

Skin DiseasesSkin and Connective Tissue DiseasesSkin ManifestationsSigns and SymptomsPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Morphine DerivativesMorphinansOpiate AlkaloidsAlkaloidsHeterocyclic CompoundsHeterocyclic Compounds, Bridged-RingHeterocyclic Compounds, 4 or More RingsHeterocyclic Compounds, Fused-RingPhenanthrenesPolycyclic Aromatic HydrocarbonsPolycyclic CompoundsBiogenic MonoaminesBiogenic AminesAminesOrganic ChemicalsEthylaminesImidazolesAzolesHeterocyclic Compounds, 1-RingAutacoidsInflammation MediatorsBiological FactorsChloridesHydrochloric AcidChlorine CompoundsInorganic ChemicalsSodium Compounds

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

September 30, 2019

First Posted

October 4, 2019

Study Start

January 15, 2020

Primary Completion

May 1, 2020

Study Completion

July 7, 2020

Last Updated

July 8, 2020

Record last verified: 2020-07

Locations