- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01245244
Morphine Modulation of The Brain's Pain Matrix (Mor2010)
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:
1. 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.
Study Overview
Detailed Description
The tests will consist of one main study (I) and one sub-study (i):
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 Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
-
Aalborg, Denmark, 9000
- Department of Gastroenterology, Aalborg Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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.
- 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
Exclusion Criteria:
- 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.
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Placebo
|
orange juice
Other Names:
|
Experimental: Morphine
|
Morphine oral mixture
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Morphine modulation of composite pain assessments
Time Frame: october 2010 - december 2012
|
october 2010 - december 2012
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Side effects of morphine
Time Frame: october 2010 - december 2012
|
october 2010 - december 2012
|
Collaborators and Investigators
Sponsor
Investigators
- Study Chair: Anne E Olesen, PhD, Aalborg University Hospital
Publications and helpful links
General 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.
- Hansen 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.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2010-020894-17
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Pain
-
Flowonix MedicalApproved for marketingBack Pain | Leg Pain | Trunk Pain | Intractable Pain | Arm Pain
-
University Hospital Schleswig-HolsteinZealand University Hospital; European Regional Development Fund; Design School...CompletedPain, Acute | Pain, Chronic | Pain Measurement | Pain, CancerGermany
-
Dow University of Health SciencesRecruitingLow Back Pain | Chronic Low-back Pain | Low Back Pain, Mechanical | Mechanical Low Back Pain | Pain, Chronic | Pain, Back | Lower Back Pain Chronic | CLBP - Chronic Low Back PainPakistan
-
Dr. Negrin University HospitalCompletedPostoperative Pain, Acute | Postoperative Pain, ChronicSpain
-
Universitat Jaume ICompletedPain, Acute | Pain, Chronic | OncologySpain
-
George Washington UniversityRecruitingCervical Fusion | Pain, Back | Pain, Neck | Myofacial PainUnited States
-
Atatürk Chest Diseases and Chest Surgery Training...RecruitingPostoperative Pain | Postoperative Pain, Acute | Postoperative Pain, Chronic | VATSTurkey
-
Janssen Research & Development, LLCCompletedPain, Radiating | Pain, Burning | Pain, Crushing | Pain, Migratory | Pain, SplittingUnited States, France, Spain, Poland, Portugal
-
University of Campinas, BrazilCompletedPREGNANCY | LUMBAR BACK PAIN | PELVIC PAIN
-
susanne beckerSNSFCompletedLow Back Pain | Pain, Acute | Pain, ChronicSwitzerland
Clinical Trials on Morphine
-
Indiana UniversityCompletedNeonatal Abstinence Syndrome | Neonatal Opioid Withdrawal Syndrome | Neonatal Opioid WithdrawalUnited States
-
Javelin PharmaceuticalsCompleted
-
Javelin PharmaceuticalsCompletedPain, PostoperativeUnited States
-
University of MonastirCompletedTitrated Versus High and Low Dose Nebulized Morphine to Reduce Pain in Emergency Settings (TIMORNEB)Acute Pain | Post-Traumatic HeadacheTunisia
-
Mahidol UniversityCompletedLung Diseases | Solitary MassThailand
-
University of Colorado, DenverCompletedScoliosis | Pain Management | Spinal FusionUnited States
-
Cukurova UniversityCompleted
-
Javelin PharmaceuticalsCompletedPost-Operative Pain | Third Molar Extraction
-
University College Hospital GalwayCompletedPain, Postoperative | Arthroplasty, Replacement, Knee
-
Rijnstate HospitalCompletedTotal Hip Replacement