Effects of Naltrexone on Nicotine Reinforcement
Information source: University of Pennsylvania
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Tobacco Dependence
Intervention: Naltrexone (Drug); Placebo (Drug)
Phase: Phase 2
Status: Completed
Sponsored by: University of Pennsylvania Official(s) and/or principal investigator(s): Caryn Lerman, Ph.D., Principal Investigator, Affiliation: University of Pennsylvania
Summary
Despite preclinical evidence supporting the role of the endogenous opioid system in the
reinforcing effects of nicotine, the efficacy of the opioid antagonist naltrexone (NTX) as a
tobacco dependence treatment remains unresolved. Research is needed to identify those
smokers for whom NTX will have the strongest beneficial effects on smoking behavior.
The research bridges existing knowledge of genetic, pharmacologic, and behavioral responses
to nicotine, and translates this knowledge to treatment for tobacco dependence. The
immediate goal was to test whether genetic variation in the mu-opioid receptor gene predicts
the effects of naltrexone (NTX) on nicotine reinforcement.
Clinical Details
Official title: Pharmacogenetic Investigation of Naltrexone
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator)
Primary outcome: Number of Nicotine Cigarette Choices Taken During the Cigarette Choice Procedure.
Detailed description:
The study was a within-subject double-blind study of the effects of naltrexone versus
placebo on the reinforcing value of nicotine, using a validated cigarette choice paradigm. A
key question was whether smokers differ in their responses based on the mu opioid receptor
gene (OPRM1) Asn40Asp (A118G) variant.
Following informed consent, 64 smokers were enrolled in the study. Of these, 60 completed
two 4-day study phases interspersed with a 5-7 day washout phase. Baseline statistics are
provided for the 64 smokers who enrolled.
Each 4-day study phase included a 3-day drug run-up and monitoring phase, then on the 4th
day participants came to our Biobehavioral Lab (BBL) where they took their final 50mg of
study medication and completed a cigarette choice paradigm. Following a washout phase, the
4-day sequence will be repeated with the alternative study medication. The order of study
medication was randomized and counterbalanced between subjects.
Eligibility
Minimum age: 18 Years.
Maximum age: 65 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
1. Participants must be greater than or equal to 18 years
2. Based on the medical history, physical and laboratory examination, female subjects
must:
1. Agree in consent to practice effective contraception during study, be status
post-bilateral tubal litigation or be post-menopausal.
2. Not be pregnant, nursing, or planning pregnancy
3. Based upon self-report, subjects must smoke greater than or equal to 10 non-menthol
cigarettes per day
4. Because the OPRM1 variant is common (25-30%) in persons of European ancestry, but
very rare in other ethnic groups (e. g., 2-9% of African Americans) it is not
scientifically justified to include members of other ethnic groups. Therefore, only
persons of European ancestry will be recruited.
5. Following orientation by the research staff, subjects must sign written informed
consent and HIPAA form.
Exclusion Criteria:
1. Current diagnosis of kidney disease or history of renal function impairment (unless
they have recent kidney function tests (within last 3 months) and approval of their
primary physician to participate in the study.)
2. Women who are pregnant, planning a pregnancy, or lactating
3. Current alcohol use > 25 standard drinks/week (this is because NTX is used to treat
alcohol dependence, and effects of NTX on alcohol consumption in alcohol dependent
subjects could have indirect effects on cigarette consumption).
4. Current medical problems for which NTX is contraindicated including: active
hepatitis (Liver Function Tests 3 times the Upper Limit of Normal).
5. History of opiate dependence (prescription drug or illicit use).
6. History of or current Diagnostic and Statistical Manual of Mental Disorders (Version
IV) (DSM IV) substance use disorders (abuse or dependence involving alcohol, cocaine,
stimulants, or benzodiazepines)
7. Diagnosis of bulimia and/or anorexia nervosa in the last year
8. Current or past use (with in past 12 months) of any medications containing NTX
(e. g., Revia, Trexan), allergy to NTX
9. Concomitant medications (e. g., monoamine oxidase inhibitors or benzodiazepines within
past 14 days, antipsychotics, antidepressants, theophylline, systemic steroids,
over-the-counter stimulants and anorectics)
Locations and Contacts
Tobacco Use Research Center, Philadelphia, Pennsylvania 19104, United States
Additional Information
Related publications: Ray R, Jepson C, Wileyto P, Patterson F, Strasser AA, Rukstalis M, Perkins K, Blendy J, Lerman C. CREB1 haplotypes and the relative reinforcing value of nicotine. Mol Psychiatry. 2007 Jul;12(7):615-7.
Starting date: March 2004
Last updated: November 12, 2013
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