Mu Opioid Receptor Genes, Remifentanil, and Pain Sensitivity
|ClinicalTrials.gov Identifier: NCT01878006|
Recruitment Status : Completed
First Posted : June 14, 2013
Last Update Posted : October 19, 2017
- Small differences in genes may alter responses to drugs. One gene that has different forms is the mu opioid receptor gene. People with one form of this gene are more sensitive to alcohol. People with a different form are sometimes more sensitive to pain. Morphine and other prescription pain pills produce pain relief by acting at the mu opioid receptor. Researchers want to see how well a drug called remifentanil can help determine sensitivity to pain. Remifentanil is a strong but short-acting pain medication that is sometimes used for anesthesia during surgery. The study will test how much the drug causes the pupils to constrict.
- To see if remifentanil can help determine pain sensitivity.
- Individuals between 21 and 55 years of age who are taking pain pills that were prescribed to treat pain from a medical or dental procedure.
- This study has a screening phase and a study phase. The screening phase involves one or two visits of 5 to 6 hours. The study phase is one outpatient visit that will take about 3 hours.
- Participants will be screened with a medical and psychiatric history and physical exam. They will be asked about drinking and drug-taking history, and any family history of alcoholism or drug abuse. Blood, urine, and breath samples will be collected.
- During the study session, participants will test their sensitivity by placing one hand in cold water. Pupil diameter will be measured before and after the sensitivity test.
- After a blood sample is taken, participants will receive the remifentanil. The sensitivity test will be repeated. Final blood samples will be collected. A brief physical exam will also be performed.
- Participants will stay in the clinic until the effects of the drug have worn off.
- About 1 week after the study session, participants will have a follow-up phone call.
|Condition or disease||Intervention/treatment||Phase|
|Polymorphism-Genetic Pain Allelic Frequencies of Genetic Markers||Genetic: OPRM1 AA118 Drug: Morphine Drug: Placebo Genetic: OPRM1 GX118||Phase 2|
Mesolimbic dopamine (DA) release is a key signal for drug reward, and endogenous opioids are thought to exert their effects in part by modulating the activity of this system. A functional (Micro)-opioid receptor (OPRM1) A118G single nucleotide polymorphism (SNP) has been associated with increased risk for heroin addiction in some studies. This polymorphism has been shown to confer differential pain sensitivity and to alter the release of DA following an alcohol challenge. The objective of this study is to examine the role of the A118G OPRM1 polymorphism for responses to a challenge of an opiate (remifentanil) with regard to psycho-physiological variables measured in the laboratory and for brain dopamine release measured by [11C]raclopride PET.
Healthy male participants who have had experience with oral prescription analgesics (e.g., Oxycontin, Vicodin, Percocet, oxycodone) will be recruited for the study. These volunteers will be screened to obtain samples of two groups of subjects: 1) persons homozygous for the major 118A allele (118AA genotype); 2) persons carrying one or two copies of the variant 118G allele (118AG or 118GG genotype, hereafter called 118GX). We will recruit up to 120 participants to obtain 40 completers per genotype for the study.
We will compare the response of these groups to a challenge with morphine given intravenously. Participants will receive a standardized IV challenge of morphine (10.0 mg/70 kg over 1 minute; morphine concentration 2 mg/ml). Pre and post injection measures will be made in two areas: 1) subjective response as measured by standardized questionnaires, and 2) measures of physiological response, including pupil response to light, respiratory rate, oxygen saturation and a pain rating from putting a hand in cold water and blood chemistries. In addition, during this visit, participants will wear the AutoSense mobile physiological monitor; parameters measured by AutoSense include respiration rate, heart rate, heart-rate variability, skin conductance, and activity level. The injection will be repeated in all participants in the PET scanner, once with morphine and once with normal saline. Dopamine release will be assessed by determining the difference between the binding potential for [11C]raclopride, a positron emitter labeled ligand which binds preferentially to D2 receptors during saline administration and its binding potential during morphine administration.
We hypothesize that 118GX subjects will have significantly different subjective response to the challenge than 118AA subjects as observed in participants receiving alcohol in a similar study (Ramchandani et al. 2011). However, the genotype effect on the response may be opposite from the effect of genotype on the alcohol response. We also hypothesize that the PET studies with [11C]raclopride will show that 118GX subjects have less dopamine release during morphine administration than 118 AA subjects.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||15 participants|
|Intervention Model:||Parallel Assignment|
|Official Title:||OPRM1 A118G SNP Effect on Striatal Dopamine Response to an IV Opiate|
|Study Start Date :||June 13, 2013|
|Actual Primary Completion Date :||April 27, 2017|
|Actual Study Completion Date :||April 27, 2017|
- Differences 11C raclopride displacement in ventral striatum based on genotype for OPRM1 [ Time Frame: immediate ]
- Differences in subjective perceptions of morphine intoxication and opiate effects based on genotype for OPRM1 [ Time Frame: immediate ]
- Differences in pupillary constriction, respiratory rate, pain response based on genotype for OPRM1 [ Time Frame: immediate ]
- Differences in neuroendocrine measures (ACTH, cortisol) based on genotype for OPRM1 [ Time Frame: Once Analyzed ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01878006
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Vijay A Ramchandani, Ph.D.||National Institute on Alcohol Abuse and Alcoholism (NIAAA)|