Phase 2 N=10 Randomized Double-blind Other

Genetic Effects on Dopamine Response to an Opiate

Polymorphism-Genetic · Pain · Addiction

Bottom Line

View on ClinicalTrials.gov: NCT01878006 ↗

Enrolled (actual)

Serious AEs

0.0%

Results posted

Oct 2018

Primary outcome: Primary: 11C Raclopride Binding Potential in Caudate — 3.25; 3.45 mCi/ml

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: Morphine (Drug); Placebo (Drug)
Age: Adult · 21+ yrs
Sex: Male
Sponsor: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Primary completion: Apr 2017

Outcome Measures

Outcome	Result	p-value
PRIMARY 11C Raclopride Binding Potential in Caudate	3.25; 3.45	—
PRIMARY 11C Raclopride Binding Potential in Nucleus Accumbens	2.68; 2.84	—
PRIMARY 11C Raclopride Binding Potential in Putamen	3.9; 4.11	—
PRIMARY 11C Raclopride Binding Potential in Ventral Pallidum	2.68; 2.94	—
SECONDARY Subjective Perception of Morphine Effect - Feel Drug	3942.8; 176	—
SECONDARY Subjective Perception of Morphine Effect - Feel High	3729.4; 175	—
SECONDARY Subjective Perception of Morphine Effect - Like Drug	3078.9; 2628.5	—
SECONDARY Subjective Perception of Morphine Effect - Want More	1601.1; 1277	—

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. 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.

Eligibility Criteria

INCLUSION CRITERIA:
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 (
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
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 ioniz

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Data sourced from ClinicalTrials.gov (NCT01878006). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.