PainPhase 4Mor2010NCT01245244
Morphine Modulation of The Brain's Pain Matrix
A Phase 4 study testing Morphine and orange juice in people with Pain, run by University of Aarhus at 1 site in Denmark.
Trial summary
The aim of the current project is to use a model of painful stimulation of skin, muscles and internal organs, where it is possible to measure activity in the brain centers that process pain simultaneously. Read more about this study
- Who is it for?
- Ages 20 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Pain
- What is being tested?
- Morphine and orange juice
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteDenmark
- Study dates
- Oct 2010to Sep 2012
- Phase
- Phase 4
- 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
- Signed and dated "Written informed consent"
- Age between 20 and 65.
- Caucasian
- That it is in the researcher's belief that the subject fully understand the contents of the study and is willing and able to comply with instructions, have the opportunity to meet with visitors, and is expected to complete the entire study. Further, it is in the researcher's beliefs (by which demanded strict action to exclusion criterion 4 and 5) that subjects with abusive tendencies are not included .
- The person must be healthy ie. without previous chronic or recurrent pain rewarding diseases. Including the person must have:
- a blood pressure is 140/90 or less. If not satisfied, a medical assessment to determine whether the person is still included, albeit with a comment and reasons recorded in the CRF.
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- a resting heart rate of at least 45 bpm. minute (measured after 5 minutes of recumbent rest). If not satisfied, a medical assessment to determine whether the person is still included, albeit with a comment and reasons recorded in the CRF.
- That women use safe contraceptive methods as the pill, coil, depot injection of progestin subdermal implantation, hormonal vaginal ring and transdermal patch.
- Negative pregnancy test prior to the conclusion of the experiment
Who cannot join
- Pregnancy.
- Known allergy to study medication
- Current or previous participation in another drug trial within 30 days before screening.
- Former participation in trials when given morphine or morphine-like substances.
- Former addiction behaviors defined as abuse of alcohol, marijuana, opiates or other narcotics or family members who have been / are a drug addict.
- Earlier pain rewarding or mental illness.
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- Expected need for medical treatment, surgery or hospitalization during the study
- Concomitant use of strong pain medications
- Use of any analgesics 24 hours before each test.
Trial locations and contacts
1 site in 1 country.
About this study
The aim of the current project is to use a model of painful stimulation of skin, muscles and internal organs, where it is possible to measure activity in the brain centers that process pain simultaneously. Magnetic resonance imaging and electroencephalography are combined to optimize the anatomical and physiological description of brain activation. During administration of morphine we will identify how different brain areas are affected. This knowledge will be used to:
- Understand the mechanisms of morphine to a greater extent than is possible today, including:
- to investigate the mechanisms of morphine versus placebo on pain signals in the spinal cord and brain. This is done by a combination of experimental pain models, neurophysiological and imaging techniques (EEG and fMRI). This can be achieved as both subjective and objective measures of the analgesic effect.
- to examine morphines effect on communication between the centers of the brain that are involved in painprocessing .
- modeling of morphine pharmacokinetics (the understanding of what the body does to the drug, such as. concentration in the blood and the brain), since this is central to understand the pharmacodynamics (the description of what the drug does to the body and thus the effect it has).
- to identify biomarkers that can predict whether healthy subjects respond to morphine by experiencing an analgesic effect.
Read the detailed description
The tests will consist of one main study (I) and one sub-study (i):
- Experiments in the painlaboratory in the gastroenterology clinic, where 40 healthy subjects will be examined with different pain tests i) Experiments in the MRI scanner, where only 20 of the 40 from the main study will be investigated in a more simple pain model. The individuals who also participate in MRI studies, will consist of those who first sign up
An equal distribution of men and women is wanted. The trial will be a double-blind, placebo-controlled crossover study in which all subjects will be investigated on two seperate days and receive respectively placebo or morphine in random order
Skin stimulation
Skin will be stimulated with thermal and electrical stimuli. Stimulated by:
- Thermal stimuli by the skin stimulated with heat with an approved termotester (Medoc termotest) or with cold, by a hand or foot immersed in ice water. This harmless ice water test is further possible to evaluate DNIC (diffuse noxious Inhibitory controls) which is part of the pain system descending inhibitory system.
- Electrical stimulation of the skin will be done by: 1) to the skin of the forearm stimulated electrically through two small surface electrodes (each approx. One cm2). There are stimulated to pain threshold, 2) via surface electrodes placed under the foot. This activates the nociceptive avert reflex as recorded by electrodes placed on the leg.
Muscle stimulation
The muscles can be stimulated by:
- mechanical stimuli by pressing the muscle with an approved pressure algometer (Somedic produktion AB, Sweden). There is an upper limit for the pressure to avoid injury.
Bone stimulation
Bone associated pain can be studied by:
- mechanical stimuli by pressing the right shin bone 15cm below the patella, medial of the tibia. Pressed with a handheld trykalgometer (Type 2, Somedic produktion AB, Sweden) with a probe size of 2mm in diameter until trial participants reach their pain tolerance threshold.
Visceral stimuli Stimuli to the rectum will be performed through the probe specifically designed for this purpose.
- mechanical stimuli will be applied by water filling a balloon which is glued on the probe. The balloon on the probe is extended to moderate pain. The expansion is done by slowly filling the balloon with 37 degrees hot water.
- Thermal stimuli will be applied by flushing the balloon with hot water (60 ° C)
- Electrical stimuli will be applied by stimulation of the mucosa with weak electrical currents (Less than 80 mA) through electrodes on the probe. This stimulus is also used for recording of evoked brain potentials.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MorphineDrug
Also called Morphine hydrochloride oral solution 2 mg/ml
Morphine oral mixture
orange juiceOther
Also called orange juice solution
orange juice
| Study group | Role | What they receive |
|---|---|---|
| Morphine | Experimental | Not described Receives: Drug: Morphine |
| Placebo | Placebo comparator | Not described Receives: Other: orange juice |
What is being measured
The primary outcome is the main question the study is designed to answer.
Morphine modulation of composite pain assessments
Measured: october 2010 - december 2012
Secondary outcomes (1)
Side effects of morphine
Measured: october 2010 - december 2012
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Nov 2010 (estimated)
- Study startOct 2010
- Primary completionSep 2012
- Study completionSep 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for PainStudies 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 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Aarhus
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Anne E Olesen, PhD, Study chair, Aalborg University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01245244
- Sponsor's protocol ID
- 2010-020894-17
- Acronym
- Mor2010
- Status last verified
- Sep 2012
- First submitted
- 24 Sep 2010
- Last updated
- 21 Sep 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Hansen TM, Olesen AE, Graversen C, Drewes AM, Frokjaer JB. The Effect of Oral Morphine on Pain-Related Brain Activation - An Experimental Functional Magnetic Resonance Imaging Study. Basic Clin Pharmacol Toxicol. 2015 Nov;117(5):316-22. doi: 10.1111/bcpt.12415. Epub 2015 May 29.
PubMed 25924691Hansen TM, Graversen C, Frokjaer JB, Olesen AE, Valeriani M, Drewes AM. Single-sweep spectral analysis of contact heat evoked potentials: a novel approach to identify altered cortical processing after morphine treatment. Br J Clin Pharmacol. 2015 Jun;79(6):926-36. doi: 10.1111/bcp.12579.
PubMed 25556985
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Morphine Modulation of The Brain's Pain Matrix
- ClinicalTrials.gov ID
- NCT01245244
- Acronym / sponsor ID
- Mor2010 / 2010-020894-17
- Conditions
- Pain
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- University of AarhusUniversity, hospital or other
- Study start
- Oct 2010
- Primary completion
- Sep 2012 (actual)
- Study completion
- Sep 2012 (actual)
- First posted
- 22 Nov 2010 (estimated)
- 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.
The aim of the current project is to use a model of painful stimulation of skin, muscles and internal organs, where it is possible to measure activity in the brain centers that process pain simultaneously. Magnetic resonance imaging and electroencephalography are combined to optimize the anatomical and physiological description of brain activation. During administration of morphine we will identify how different brain areas are affected. This knowledge will be used to:
- Understand the mechanisms of morphine to a greater extent than is possible today, including:
- to investigate the mechanisms of morphine versus placebo on pain signals in the spinal cord and brain. This is done by a combination of experimental pain models, neurophysiological and imaging techniques (EEG and fMRI). This can be achieved as both subjective and objective measures of the analgesic effect.
- to examine morphines effect on communication between the centers of the brain that are involved in painprocessing .
- modeling of morphine pharmacokinetics (the understanding of what the body does to the drug, such as. concentration in the blood and the brain), since this is central to understand the pharmacodynamics (the description of what the drug does to the body and thus the effect it has).
- to identify biomarkers that can predict whether healthy subjects respond to morphine by experiencing an analgesic effect.
Detailed description
The tests will consist of one main study (I) and one sub-study (i):
- Experiments in the painlaboratory in the gastroenterology clinic, where 40 healthy subjects will be examined with different pain tests i) Experiments in the MRI scanner, where only 20 of the 40 from the main study will be investigated in a more simple pain model. The individuals who also participate in MRI studies, will consist of those who first sign up
An equal distribution of men and women is wanted. The trial will be a double-blind, placebo-controlled crossover study in which all subjects will be investigated on two seperate days and receive respectively placebo or morphine in random order
Skin stimulation
Skin will be stimulated with thermal and electrical stimuli. Stimulated by:
- Thermal stimuli by the skin stimulated with heat with an approved termotester (Medoc termotest) or with cold, by a hand or foot immersed in ice water. This harmless ice water test is further possible to evaluate DNIC (diffuse noxious Inhibitory controls) which is part of the pain system descending inhibitory system.
- Electrical stimulation of the skin will be done by: 1) to the skin of the forearm stimulated electrically through two small surface electrodes (each approx. One cm2). There are stimulated to pain threshold, 2) via surface electrodes placed under the foot. This activates the nociceptive avert reflex as recorded by electrodes placed on the leg.
Muscle stimulation
The muscles can be stimulated by:
- mechanical stimuli by pressing the muscle with an approved pressure algometer (Somedic produktion AB, Sweden). There is an upper limit for the pressure to avoid injury.
Bone stimulation
Bone associated pain can be studied by:
- mechanical stimuli by pressing the right shin bone 15cm below the patella, medial of the tibia. Pressed with a handheld trykalgometer (Type 2, Somedic produktion AB, Sweden) with a probe size of 2mm in diameter until trial participants reach their pain tolerance threshold.
Visceral stimuli Stimuli to the rectum will be performed through the probe specifically designed for this purpose.
- mechanical stimuli will be applied by water filling a balloon which is glued on the probe. The balloon on the probe is extended to moderate pain. The expansion is done by slowly filling the balloon with 37 degrees hot water.
- Thermal stimuli will be applied by flushing the balloon with hot water (60 ° C)
- Electrical stimuli will be applied by stimulation of the mucosa with weak electrical currents (Less than 80 mA) through electrodes on the probe. This stimulus is also used for recording of evoked brain potentials.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Morphine | Experimental | Drug: Morphine |
| Placebo | Placebo comparator | Other: orange juice |
Who may qualify
- Ages
- 20 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Signed and dated "Written informed consent"
- Age between 20 and 65.
- Caucasian
- That it is in the researcher's belief that the subject fully understand the contents of the study and is willing and able to comply with instructions, have the opportunity to meet with visitors, and is expected to complete the entire study. Further, it is in the researcher's beliefs (by which demanded strict action to exclusion criterion 4 and 5) that subjects with abusive tendencies are not included .
- The person must be healthy ie. without previous chronic or recurrent pain rewarding diseases. Including the person must have:
Key exclusion criteria (9 listed)
- Pregnancy.
- Known allergy to study medication
- Current or previous participation in another drug trial within 30 days before screening.
- Former participation in trials when given morphine or morphine-like substances.
- Former addiction behaviors defined as abuse of alcohol, marijuana, opiates or other narcotics or family members who have been / are a drug addict.
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 |
|---|---|---|
| MorphineAlso: Morphine hydrochloride oral solution 2 mg/mlMorphine oral mixture | Drug | Morphine |
| orange juiceAlso: orange juice solutionorange juice | Other | Placebo |
Primary outcome
Morphine modulation of composite pain assessments
Time frame: october 2010 - december 2012
1 secondary outcome
Side effects of morphine
Time frame: october 2010 - december 2012
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 21 Sep 2012.
- Derived from this study: PubMed 25924691Hansen TM, Olesen AE, Graversen C, Drewes AM, Frokjaer JB. The Effect of Oral Morphine on Pain-Related Brain Activation - An Experimental Functional Magnetic Resonance Imaging Study. Basic Clin Pharmacol Toxicol. 2015 Nov;117(5):316-22. doi: 10.1111/bcpt.12415. Epub 2015 May 29.
- Derived from this study: PubMed 25556985Hansen TM, Graversen C, Frokjaer JB, Olesen AE, Valeriani M, Drewes AM. Single-sweep spectral analysis of contact heat evoked potentials: a novel approach to identify altered cortical processing after morphine treatment. Br J Clin Pharmacol. 2015 Jun;79(6):926-36. doi: 10.1111/bcp.12579.
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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.
Anne E Olesen, PhD study chair
Aalborg University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Morphine and orange juice in people with Pain, run by University of Aarhus 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 9 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 21 Sep 2012. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Morphine modulation of composite pain assessments (time frame: october 2010 - december 2012). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01245244, which also lists 2 linked publications.
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 21 Sep 2012.