Polymorphism-GeneticPhase 2NCT01878006
Genetic Effects on Dopamine Response to an Opiate
A Phase 2 study testing Morphine in people with Polymorphism-Genetic and Pain, run by National Institute on Alcohol Abuse and Alcoholism (NIAAA) at 1 site in United States.
Trial summary
Background: 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. Read more about this study
- Who is it for?
- Ages 21 to 55 years, men only
- Conditions the study is for
- Polymorphism-Genetic, Pain, Addiction
- What is being tested?
- Morphine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Jun 2013to 27 Apr 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 21 to 55 years
- Men only
- No healthy volunteers
- Adult
Who may be able to join
- Male participants between 21-55 years of age.
- Good health as determined by medical history, physical exam, EKG and lab tests.
- Current non-smokers or light smokers or e-cigarette users (<20 cig/week) who can easily abstain from smoking or using e-cigarettes for 1-2 days/week.
- Current non-drinkers or social drinkers who do not meet past or current DSM IV criteria for alcohol abuse or alcohol dependence.
- An equal number of final participants will be of OPRM1 118 A/A vs. 118A/G or 118G/G genotype. This means that after the first group (n40) is complete then only participants with the required genotype for the other group will be included.
- Prior opiate use, at least one experience with one of the opiates listed in Appendix 1 of the protocol.
- Comprehension/fluency with English Language.
Who cannot join
- Current or prior history of any significant disease, including cardiovascular, respiratory, gastrointestinal, hepatic, renal, endocrine, or reproductive disorders, or a positive hepatitis or HIV test at screening, disorders that could make administration of an opiate more risky (e.g., asthma, COPD, sleep apnea, or other breathing disorders; liver or kidney disease; thyroid disorder; trouble swallowing, or a blockage in the digestive tract (stomach or intestines); neurologic disorders (e.g., a history of head injury or brain tumor, epilepsy or other seizure disorder, CVA, migraine in treatment, etc.); low blood pressure; hypertension; neuromuscular disorder; gallbladder disease; Addison's disease or other adrenal gland disorders; enlarged prostate, urination problems)
- Current Axis-I psychiatric illness as determined by the Structured Clinical Interview for DSM IV disorders (SCID).
- Current or prior history of any alcohol or drug dependence as determined by the Structured Clinical Interview for DSM IV disorders (SCID).
- Positive result on urine screen for illicit drugs.
- Medication Use:
- Current chronic prescription or over the counter medications or use of prescription or OTC medications known to interact with dopamine receptors within 2 weeks of the study
Show all 16Show fewer
- Drugs known to inhibit or induce enzymes that metabolize opiates should not be used for 4 weeks prior to the study. These include chlorzoxazone, isoniazid, metronidazole and disulfiram.
- Cough-and-cold preparations that contain anti-histamines or opiate pain medicines will be withheld for at least 72 hours prior to each study session.
- Drugs that may interfere with the BOLD MRI signal within 2 weeks of the study. These include, but may not be limited to: muscle relaxants or respiratory, cardiovascular or anticonvulsant medications
- Morbid obesity (BMI >40 kg/m2)
- Previous negative effects of opioid administration
- Presence of certain implanted devices (cardiac pacemaker or neurostimulator, some artificial joints, metal pins, surgical clips or other implanted metal parts), body morphology, or claustrophobia. Justification: Implanted devices may increase the risk of MRI scanning and/or adversely affect the quality of the data; body morphology may prevent optimal positioning in the scanner and thus affect the quality of the data; participants with claustrophobia may find the MRI scan too unpleasant and may exhibit excess movement that will adversely affect the quality of the data. Assessment tool(s): Prospective participants will fill out an MRI screening questionnaire and undergo an interview with an MR technologist. Questions concerning suitability for scanning will be referred to the Medical Advisory Investigator. Prospective participants will be questioned about symptoms of claustrophobia and placed in the mock scanner during their first visit to assess for possible difficulty tolerating the confinement of the scanner and for ability to fit into the scanner.
- Conditions restricting participant's ability to lie flat for up to two hours (such as coagulopathies, superficial or deep vein thrombosis, or musculoskeletal abnormalities). Justification: PET scanning sessions require participants to lie flat on their backs and remain perfectly still for approximately two hours. Therefore, conditions that would make that difficult (e.g., chronic back pain, significant scoliosis) or dangerous (e.g., familial hypercoagulability syndrome, history of thrombosis) will be exclusionary. Assessment tool(s): History and physical examination by a qualified IRP clinician, supplemented with a trial of lying in the mock scanner to assess comfort.
- Head trauma leading to loss of consciousness for more than 5 min or hospitalization
- Exposure to ionizing radiation from research studies that, in combination with the study tracer, would result in cumulative exposure of >5 rem within the previous 12 month period
- Self-reported and/or observed signs, symptoms, or diagnosis of Raynaud's or Buerger's disease (e.g., pain in hands or feet at times of rest, during/following cold exposure or stress, any significant color changes in hands or toes). Additionally, medical staff will be present to watch for these symptoms during the actual cold pressor test.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: OPRM1 A118G SNP Effect on Striatal Dopamine Response to an IV Opiate
Background:
- 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 the effect of morphine on brain reward and subjective effects. Morphine is a strong but short-acting pain medication that is sometimes used for anesthesia during surgery.
Read more
Objectives:
- To compare the effect of morphine on brain measures of dopamine release using imaging.
Eligibility:
- Individuals between 21 and 55 years of age who have previously taken pain pills prescribed to treat pain from a medical or dental procedure.
Design:
- 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 consists of 4 study visits. Each study visit will take about 8 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 first study visit, an MRI scan may be performed, questionnaires completed, and a blood sample collected for genetic testing.
- During study visit 2, participants will test their pain sensitivity by placing one hand in cold water. Pupil diameter will be measured after the sensitivity test. After a blood sample is taken, participants will receive the morphine or a salt solution. The sensitivity test and pupil diameter test will be repeated. Final blood samples will be collected. A brief physical exam will also be performed.
- During study visits 3 and 4, participants will receive morphine or a salt solution during a PET scan. Questionnaires to assess subjective effects will be administered. 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 after study visits 2, 3, and 4.
- About 1 week after the study session, participants will have a follow-up phone call.
Read the detailed description
Objectives
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 µ-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 (morphine) with regard to psycho-physiological variables measured in the laboratory and for brain dopamine release measured by [11C]raclopride PET.
Study Population
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.
Design
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.
Outcome measures
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.
- Conditions
- Polymorphism-Genetic, Pain, Addiction
- Being tested
- Morphine, Placebo
- Keywords
- Opiate Receptor, Genotype, PET Imaging
- Medical subject headings
- Pain, Behavior, Addictive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MorphineDrug
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Morphine | Experimental | Morphine injection 10 mg/70kg Receives: Drug: Morphine |
| Placebo | Placebo comparator | Saline injection Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
11C Raclopride Binding Potential in Caudate
Binding potential measured using regions-of-interest analysis of PET data. Parametric Binding Potential (BPND) images were obtained using the Simple Reference Tissue Model 2 (SRTM2), with cerebellum as the reference region. BPND is computed in units of mCi/ml reflecting the radioactivity (milliCuries or mCi) per unit volume (milliliters or ml) in specific brain regions. Reduction in raclopride binding is attributed to competition with endogenous dopamine, and has been shown to be proportional to the magnitude of Dopamine (DA) release.
Measured: 90 minutes following injection
11C Raclopride Binding Potential in Nucleus Accumbens
Binding potential measured using regions-of-interest analysis of PET data. Parametric Binding Potential (BPND) images were obtained using the Simple Reference Tissue Model 2 (SRTM2), with cerebellum as the reference region. BPND is computed in units of mCi/ml reflecting the radioactivity (milliCuries or mCi) per unit volume (milliliters or ml) in specific brain regions. Reduction in raclopride binding is attributed to competition with endogenous dopamine, and has been shown to be proportional to the magnitude of Dopamine (DA) release.
Measured: 90 minutes following injection
11C Raclopride Binding Potential in Putamen
Binding potential measured using regions-of-interest analysis of PET data. Parametric Binding Potential (BPND) images were obtained using the Simple Reference Tissue Model 2 (SRTM2), with cerebellum as the reference region. BPND is computed in units of mCi/ml reflecting the radioactivity (milliCuries or mCi) per unit volume (milliliters or ml) in specific brain regions. Reduction in raclopride binding is attributed to competition with endogenous dopamine, and has been shown to be proportional to the magnitude of Dopamine (DA) release.
Measured: 90 minutes following injection
11C Raclopride Binding Potential in Ventral Pallidum
Binding potential measured using regions-of-interest analysis of PET data. Parametric Binding Potential (BPND) images were obtained using the Simple Reference Tissue Model 2 (SRTM2), with cerebellum as the reference region. BPND is computed in units of mCi/ml reflecting the radioactivity (milliCuries or mCi) per unit volume (milliliters or ml) in specific brain regions. Reduction in raclopride binding is attributed to competition with endogenous dopamine, and has been shown to be proportional to the magnitude of Dopamine (DA) release.
Measured: 90 minutes following injection
Secondary outcomes (4)
Subjective Perception of Morphine Effect - Feel Drug
Area under the curve of the subjective perception-time course - Feel Drug. Subjective responses as measured by the Drug Effects Questionnaire [DEQ]. The DEQ consists of simple, face-valid, visual analog scale (VAS) questions on which people report their subjective states after ingesting a substance. The analog scale of responses ranges from "not at all" to "extremely", and the numeric scale ranges from 0 to 100. Due to skewness of individual time points; areas under the curve (AUC) for these ratings across individual time points (0, 10, 20, 30, 40, 50 and 60 min) were compared. AUC is computed using the trapezoidal rule and has a range of values from 0 to 5500, where 0 reflects no subjective perception at any time point and 5500 reflects maximal subjective perception (score of 100) at all time points after drug administration.
Measured: 60 minutes following injection
Subjective Perception of Morphine Effect - Feel High
Area under the curve of the subjective perception-time course - Feel High. Subjective responses as measured by the Drug Effects Questionnaire [DEQ]. The DEQ consists of simple, face-valid, visual analog scale (VAS) questions on which people report their subjective states after ingesting a substance. The analog scale of responses ranges from "not at all" to "extremely", and the numeric scale ranges from 0 to 100. Due to skewness of individual time points; areas under the curve (AUC) for these ratings across individual time points (0, 10, 20, 30, 40, 50 and 60 min) were compared. AUC is computed using the trapezoidal rule and has a range of values from 0 to 5500, where 0 reflects no subjective perception at any time point and 5500 reflects maximal subjective perception (score of 100) at all time points after drug administration.
Measured: 60 minutes following injection
Subjective Perception of Morphine Effect - Like Drug
Area under the curve of the subjective perception-time course - Like Drug. Subjective responses as measured by the Drug Effects Questionnaire [DEQ]. The DEQ consists of simple, face-valid, visual analog scale (VAS) questions on which people report their subjective states after ingesting a substance. The analog scale of responses ranges from "not at all" to "extremely", and the numeric scale ranges from 0 to 100. Due to skewness of individual time points; areas under the curve (AUC) for these ratings across individual time points (0, 10, 20, 30, 40, 50 and 60 min) were compared. AUC is computed using the trapezoidal rule and has a range of values from 0 to 5500, where 0 reflects no subjective perception at any time point and 5500 reflects maximal subjective perception (score of 100) at all time points after drug administration.
Measured: 60 minutes following injection
Subjective Perception of Morphine Effect - Want More
Area under the curve of the subjective perception-time course - Want More. Subjective responses as measured by the Drug Effects Questionnaire [DEQ]. The DEQ consists of simple, face-valid, visual analog scale (VAS) questions on which people report their subjective states after ingesting a substance. The analog scale of responses ranges from "not at all" to "extremely", and the numeric scale ranges from 0 to 100. Due to skewness of individual time points; areas under the curve (AUC) for these ratings across individual time points (0, 10, 20, 30, 40, 50 and 60 min) were compared. AUC is computed using the trapezoidal rule and has a range of values from 0 to 5500, where 0 reflects no subjective perception at any time point and 5500 reflects maximal subjective perception (score of 100) at all time points after drug administration.
Measured: 60 minutes following injection
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2013 (estimated)
- Study start13 Jun 2013
- Primary completion27 Apr 2017
- Study completion27 Apr 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Polymorphism-GeneticStudies 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 2
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Crossover study - participants receive active and placebo treatments in randomized order.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Sponsor type
- US National Institutes of Health
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Sponsor
- Investigators
- Vijay A Ramchandani, Ph.D., Principal investigator, National Institute on Alcohol Abuse and Alcoholism (NIAAA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01878006
- Sponsor's protocol ID
- 130061
- Other IDs
- 13-AA-0061
- Status last verified
- Mar 2021
- First submitted
- 12 Jun 2013
- Last updated
- 1 Apr 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: The protocol does not outline a plan for data sharing. Samples and data will be transferred to a repository for analysis of exploratory outcomes beyond the primary objectives of the study, after IRB approval.
Publications
Barr CS, Schwandt M, Lindell SG, Chen SA, Goldman D, Suomi SJ, Higley JD, Heilig M. Association of a functional polymorphism in the mu-opioid receptor gene with alcohol response and consumption in male rhesus macaques. Arch Gen Psychiatry. 2007 Mar;64(3):369-76. doi: 10.1001/archpsyc.64.3.369.
PubMed 17339526Bart G, Heilig M, LaForge KS, Pollak L, Leal SM, Ott J, Kreek MJ. Substantial attributable risk related to a functional mu-opioid receptor gene polymorphism in association with heroin addiction in central Sweden. Mol Psychiatry. 2004 Jun;9(6):547-9. doi: 10.1038/sj.mp.4001504. No abstract available.
PubMed 15037869Callaghan RC, Cunningham JK, Verdichevski M, Sykes J, Jaffer SR, Kish SJ. All-cause mortality among individuals with disorders related to the use of methamphetamine: a comparative cohort study. Drug Alcohol Depend. 2012 Oct 1;125(3):290-4. doi: 10.1016/j.drugalcdep.2012.03.004. Epub 2012 Apr 13.
PubMed 22503689Spagnolo PA, Kimes A, Schwandt ML, Shokri-Kojori E, Thada S, Phillips KA, Diazgranados N, Preston KL, Herscovitch P, Tomasi D, Ramchandani VA, Heilig M. Striatal Dopamine Release in Response to Morphine: A [11C]Raclopride Positron Emission Tomography Study in Healthy Men. Biol Psychiatry. 2019 Sep 1;86(5):356-364. doi: 10.1016/j.biopsych.2019.03.965. Epub 2019 Mar 15.
PubMed 31097294
Study at a glance
From the registry record, last updated by the sponsor on 1 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- OPRM1 A118G SNP Effect on Striatal Dopamine Response to an IV Opiate
- ClinicalTrials.gov ID
- NCT01878006
- Acronym / sponsor ID
- 130061
- Conditions
- Polymorphism-Genetic, Pain, Addiction
- Keywords
- Opiate Receptor, Genotype, PET Imaging
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)US National Institutes of Health
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- 13 Jun 2013
- Primary completion
- 27 Apr 2017 (actual)
- Study completion
- 27 Apr 2017 (actual)
- First posted
- 14 Jun 2013 (estimated)
- Results
- Posted 23 Oct 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
- 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 the effect of morphine on brain reward and subjective effects. Morphine is a strong but short-acting pain medication that is sometimes used for anesthesia during surgery.
Objectives:
- To compare the effect of morphine on brain measures of dopamine release using imaging.
Eligibility:
- Individuals between 21 and 55 years of age who have previously taken pain pills prescribed to treat pain from a medical or dental procedure.
Design:
- 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 consists of 4 study visits. Each study visit will take about 8 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 first study visit, an MRI scan may be performed, questionnaires completed, and a blood sample collected for genetic testing.
- During study visit 2, participants will test their pain sensitivity by placing one hand in cold water. Pupil diameter will be measured after the sensitivity test. After a blood sample is taken, participants will receive the morphine or a salt solution. The sensitivity test and pupil diameter test will be repeated. Final blood samples will be collected. A brief physical exam will also be performed.
- During study visits 3 and 4, participants will receive morphine or a salt solution during a PET scan. Questionnaires to assess subjective effects will be administered. 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 after study visits 2, 3, and 4.
- About 1 week after the study session, participants will have a follow-up phone call.
Detailed description
Objectives
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 µ-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 (morphine) with regard to psycho-physiological variables measured in the laboratory and for brain dopamine release measured by [11C]raclopride PET.
Study Population
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.
Design
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.
Outcome measures
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 design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Crossover study - participants receive active and placebo treatments in randomized order.
| Arm | Type | Receives |
|---|---|---|
| Morphine | Experimental | Drug: MorphineMorphine injection 10 mg/70kg |
| Placebo | Placebo comparator | Drug: PlaceboSaline injection |
Who may qualify
- Ages
- 21 to 55 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
Key exclusion criteria (16 listed)
- Current or prior history of any significant disease, including cardiovascular, respiratory, gastrointestinal, hepatic, renal, endocrine, or reproductive disorders, or a positive hepatitis or HIV test at screening, disorders that could make administration of an opiate more risky (e.g., asthma, COPD, sleep apnea, or other breathing disorders; liver or kidney disease; thyroid disorder; trouble swallowing, or a blockage in the digestive tract (stomach or intestines); neurologic disorders (e.g., a history of head injury or brain tumor, epilepsy or other seizure disorder, CVA, migraine in treatment, etc.); low blood pressure; hypertension; neuromuscular disorder; gallbladder disease; Addison's disease or other adrenal gland disorders; enlarged prostate, urination problems)
- Current Axis-I psychiatric illness as determined by the Structured Clinical Interview for DSM IV disorders (SCID).
- Current or prior history of any alcohol or drug dependence as determined by the Structured Clinical Interview for DSM IV disorders (SCID).
- Positive result on urine screen for illicit drugs.
- Medication Use:
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 |
|---|---|---|
| Morphine | Drug | Morphine |
| Placebo | Drug | Placebo |
Primary outcome
11C Raclopride Binding Potential in Caudate
Time frame: 90 minutes following injection
Binding potential measured using regions-of-interest analysis of PET data. Parametric Binding Potential (BPND) images were obtained using the Simple Reference Tissue Model 2 (SRTM2), with cerebellum as the reference region. BPND is computed in units of mCi/ml reflecting the radioactivity (milliCuries or mCi) per unit volume (milliliters or ml) in specific brain regions. Reduction in raclopride binding is attributed to competition with endogenous dopamine, and has been shown to be proportional to the magnitude of Dopamine (DA) release.
11C Raclopride Binding Potential in Nucleus Accumbens
Time frame: 90 minutes following injection
Binding potential measured using regions-of-interest analysis of PET data. Parametric Binding Potential (BPND) images were obtained using the Simple Reference Tissue Model 2 (SRTM2), with cerebellum as the reference region. BPND is computed in units of mCi/ml reflecting the radioactivity (milliCuries or mCi) per unit volume (milliliters or ml) in specific brain regions. Reduction in raclopride binding is attributed to competition with endogenous dopamine, and has been shown to be proportional to the magnitude of Dopamine (DA) release.
11C Raclopride Binding Potential in Putamen
Time frame: 90 minutes following injection
Binding potential measured using regions-of-interest analysis of PET data. Parametric Binding Potential (BPND) images were obtained using the Simple Reference Tissue Model 2 (SRTM2), with cerebellum as the reference region. BPND is computed in units of mCi/ml reflecting the radioactivity (milliCuries or mCi) per unit volume (milliliters or ml) in specific brain regions. Reduction in raclopride binding is attributed to competition with endogenous dopamine, and has been shown to be proportional to the magnitude of Dopamine (DA) release.
11C Raclopride Binding Potential in Ventral Pallidum
Time frame: 90 minutes following injection
Binding potential measured using regions-of-interest analysis of PET data. Parametric Binding Potential (BPND) images were obtained using the Simple Reference Tissue Model 2 (SRTM2), with cerebellum as the reference region. BPND is computed in units of mCi/ml reflecting the radioactivity (milliCuries or mCi) per unit volume (milliliters or ml) in specific brain regions. Reduction in raclopride binding is attributed to competition with endogenous dopamine, and has been shown to be proportional to the magnitude of Dopamine (DA) release.
4 secondary outcomes
Subjective Perception of Morphine Effect - Feel Drug
Time frame: 60 minutes following injection
Subjective Perception of Morphine Effect - Feel High
Time frame: 60 minutes following injection
Subjective Perception of Morphine Effect - Like Drug
Time frame: 60 minutes following injection
Subjective Perception of Morphine Effect - Want More
Time frame: 60 minutes following injection
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 17339526Barr CS, Schwandt M, Lindell SG, Chen SA, Goldman D, Suomi SJ, Higley JD, Heilig M. Association of a functional polymorphism in the mu-opioid receptor gene with alcohol response and consumption in male rhesus macaques. Arch Gen Psychiatry. 2007 Mar;64(3):369-76. doi: 10.1001/archpsyc.64.3.369.
- Background: PubMed 15037869Bart G, Heilig M, LaForge KS, Pollak L, Leal SM, Ott J, Kreek MJ. Substantial attributable risk related to a functional mu-opioid receptor gene polymorphism in association with heroin addiction in central Sweden. Mol Psychiatry. 2004 Jun;9(6):547-9. doi: 10.1038/sj.mp.4001504. No abstract available.
- Background: PubMed 22503689Callaghan RC, Cunningham JK, Verdichevski M, Sykes J, Jaffer SR, Kish SJ. All-cause mortality among individuals with disorders related to the use of methamphetamine: a comparative cohort study. Drug Alcohol Depend. 2012 Oct 1;125(3):290-4. doi: 10.1016/j.drugalcdep.2012.03.004. Epub 2012 Apr 13.
- Derived from this study: PubMed 31097294Spagnolo PA, Kimes A, Schwandt ML, Shokri-Kojori E, Thada S, Phillips KA, Diazgranados N, Preston KL, Herscovitch P, Tomasi D, Ramchandani VA, Heilig M. Striatal Dopamine Release in Response to Morphine: A [11C]Raclopride Positron Emission Tomography Study in Healthy Men. Biol Psychiatry. 2019 Sep 1;86(5):356-364. doi: 10.1016/j.biopsych.2019.03.965. Epub 2019 Mar 15.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided. The protocol does not outline a plan for data sharing. Samples and data will be transferred to a repository for analysis of exploratory outcomes beyond the primary objectives of the study, after IRB approval.
Related trials for Polymorphism-Genetic
Enrolling by invitation
The Efficacy of Pedometer-motivated Physical Activity for the Management of Patients With MASLD.
Daily Step Count, MASLD
Enrolling by invitation
Effects of Exercise Training and Genetic Factors in Hypertensive Patients with Obstructive Sleep Apnea Sleep
Exercise Training, Genetic Polymorphism
Recruiting
Effect of Mutations in T2DM Susceptibility Genes on the Expression of Susceptibility Genes in Patients With T2DM and Controls
Type 2 Diabetes Mellitus, Gene Polymorphisms
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.
Vijay A Ramchandani, Ph.D. principal investigator
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Morphine in people with Polymorphism-Genetic and Pain, run by National Institute on Alcohol Abuse and Alcoholism (NIAAA) at 1 site in United States.
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 7 inclusion and 16 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 1 Apr 2021. 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 United States. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Oct 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
11C Raclopride Binding Potential in Caudate (time frame: 90 minutes following injection). 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?
On the ClinicalTrials.gov record for NCT01878006, which also lists 4 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 1 Apr 2021; AzTrials last refreshed its copy on 2 Nov 2026.