MorphineNCT04115462
A Relation of Morphine-induced Itch and Pain Processing
A study testing Morphine, Histamine and Cowhage (Mucuna Pruriens) in people with Morphine and Itch, run by Aalborg University at 1 site in Denmark.
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. Read more about this study
- Who is it for?
- Ages 20 to 65 yearsHealthy volunteers can take part
- What is being tested?
- Morphine, Histamine and Cowhage (Mucuna Pruriens)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteDenmark
- Study dates
- 15 Jan 2020to 7 Jul 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy men and women in the age of 20-65 years
- The participants must be able to speak and understand English
Who cannot join
- 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
Show all 9Show fewer
- Participating in another study where investigational drug is used
- Participants had known allergy/discomfort to morphine
- Lack of ability to cooperate
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Mech-Sense, Medicinsk Gastroenterologisk ambulatorium, Medicineshus, Aalborg Universitetshospitalet,
Aalborg, North Denmark, 9000
About this study
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)
In This experiment, the investigators would like to test the two following hypotheses regarding the mechanisms by which opioids cause itch:
- Opioids cause itch by a spinal disinhibition mechanism (central nervous system (CNS) effect).
- 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).
Read the 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.
- Being tested
- Morphine, Placebo oral tablet, Histamine, Cowhage (Mucuna Pruriens), isotonic saline
- Medical subject headings
- Pruritus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MorphineDrug
A 20 mg tablet of morphine
Placebo oral tabletDrug
Matching tablet of placebo
HistamineDrug
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 salineDrug
Also called 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.
HistamineDrug
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)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
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Morphine; Drug: Histamine; Drug: 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. Receives: Drug: Placebo oral tablet; Drug: Histamine; Drug: Cowhage (Mucuna Pruriens); Drug: isotonic saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Microvascular reactivity
The evoked cutaneous inflammation (quantified by superficial blood perfusion) will be measured by full-field laser perfusion imaging.
Measured: 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.
Measured: 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'.
Measured: 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'.
Measured: 1 minute after every itch inductions
Secondary outcomes (4)
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.
Measured: 10 minutes before morphine/placebo administration
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.
Measured: 60 minutes after morphine/placebo administration
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.
Measured: 10 minutes before morphine/placebo administration
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.
Measured: 60 minutes after morphine/placebo administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2019
- Study start15 Jan 2020
- Primary completion1 May 2020
- Study completion7 Jul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MorphineStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aalborg University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Silvia Lo Vecchio, Aalborg University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04115462
- Sponsor's protocol ID
- N-20190049
- Status last verified
- Jul 2020
- First submitted
- 30 Sep 2019
- Last updated
- 8 Jul 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT04115462
- Acronym / sponsor ID
- N-20190049
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Aalborg UniversityUniversity, hospital or other
- Study start
- 15 Jan 2020 (actual)
- Primary completion
- 1 May 2020 (actual)
- Study completion
- 7 Jul 2020 (actual)
- First posted
- 4 Oct 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In This experiment, the investigators would like to test the two following hypotheses regarding the mechanisms by which opioids cause itch:
- Opioids cause itch by a spinal disinhibition mechanism (central nervous system (CNS) effect).
- 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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Morphine | Active comparator | Drug: Morphine, Drug: Histamine, Drug: Cowhage (Mucuna Pruriens), Drug: isotonic salineEach 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. |
| Placebo | Placebo comparator | Drug: Placebo oral tablet, Drug: Histamine, Drug: Cowhage (Mucuna Pruriens), Drug: isotonic salineEach 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. |
Who may qualify
- Ages
- 20 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Healthy men and women in the age of 20-65 years
- The participants must be able to speak and understand English
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MorphineA 20 mg tablet of morphine | Drug | Morphine |
| Placebo oral tabletMatching tablet of placebo | Drug | Placebo |
| HistamineHistaminergic 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. | Drug | Morphine, Placebo |
| 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 | Drug | Morphine, Placebo |
| isotonic salineAlso: salineA 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. | Drug | Morphine, Placebo |
| HistamineHistaminergic 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. | Drug | Morphine, Placebo |
| 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 | Drug | Morphine, Placebo |
Primary outcome
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.
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.
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'.
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'.
4 secondary outcomes
Cold (CPT) and heat (HPT) pain thesholds
Time frame: 10 minutes before morphine/placebo administration
Cold (CPT) and heat (HPT) pain thesholds
Time frame: 60 minutes after morphine/placebo administration
Pressure Pain Threshold
Time frame: 10 minutes before morphine/placebo administration
Pressure Pain Threshold
Time frame: 60 minutes after morphine/placebo administration
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jul 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Morphine, Histamine and Cowhage (Mucuna Pruriens) in people with Morphine and Itch, run by Aalborg University at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Microvascular reactivity (time frame: Before and 70 minutes after morphine/placebo administration). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jul 2020.