Effects of Naltrexone on Nicotine Reinforcement

NCT00270231 | Completed Phase 2 Results

• 2 other identifiers: 800810R01DA017555
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Tobacco Dependence

Keywords

within-subjects, crossover, laboratory study; Naltrexone vs. Placebo

Outcome Measures

Primary Outcomes (1)

• Number of Nicotine Cigarette Choices Taken During the Cigarette Choice Procedure.

  On day 4 of each study medication period, participants completed a cigarette choice procedure where the subject is asked to take 4 puffs from a nicotinized (nicotine-containing) or a denicotinized (no nicotine) cigarette every 30 minutes for 2 hours (maximum of 24 puffs). The outcome variable is the number of nicotine cigarette choices or puffs out of 24 total puffs during these cigarette choice procedures. Subjects who had the A/A genotype took an average of 18.5 puffs from the nicotine-containing cigarettes. Subjects with the A/G or G/G genotypes took an average of 16.2 puffs from the nicotine-containing cigarettes.

  2 hours

Study Arms (2)

Naltrexone

ACTIVE COMPARATOR

All participants took naltrexone during one of the two 4-day study medication periods. Both 4-day study medication periods were randomized and counterbalanced between naltrexone and placebo; all study medication periods were separated by a 5-7 day washout period. Dosing of the naltrexone was the same for all participants: Day 1: 12.5mg, Day 2: 25mg, Days 3 and 4: 50mg.

Drug: Naltrexone

Placebo

PLACEBO COMPARATOR

All participants took a placebo (sugar pill) during one of the two 4-day study medication periods. Both 4-day study medication periods were randomized and counterbalanced between naltrexone and placebo. Placebo capsules matched the naltrexone in color, weight and inactive ingredients. The only difference the lack of active naltrexone in each capsule.

Drug: Placebo

Interventions

Naltrexone DRUG

All participants took naltrexone during one of the two 4-day study medication periods. Both 4-day study medication periods were randomized and counterbalanced between naltrexone and placebo; all study medication periods were separated by a 5-7 day washout period. Dosing of the naltrexone was the same for all participants: Day 1: 12.5mg, Day 2: 25mg, Days 3 and 4: 50mg.

Also known as: Revia or Trexan

Naltrexone

Placebo DRUG

All participants took a placebo (sugar pill) during one of the two 4-day study medication periods. Both 4-day study medication periods were randomized and counterbalanced between naltrexone and placebo. Placebo capsules matched the naltrexone in color, weight and inactive ingredients. The only difference the lack of active naltrexone in each capsule.

Also known as: Sugar pill; inactive medication

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must be greater than or equal to 18 years
• Based on the medical history, physical and laboratory examination, female subjects must:
• Agree in consent to practice effective contraception during study, be status post-bilateral tubal litigation or be post-menopausal.
• Not be pregnant, nursing, or planning pregnancy
• Based upon self-report, subjects must smoke greater than or equal to 10 non-menthol cigarettes per day
• 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.
• Following orientation by the research staff, subjects must sign written informed consent and HIPAA form.

You may not qualify if:

• 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.)
• Women who are pregnant, planning a pregnancy, or lactating
• 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).
• Current medical problems for which NTX is contraindicated including: active hepatitis (Liver Function Tests 3 times the Upper Limit of Normal).
• History of opiate dependence (prescription drug or illicit use).
• 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)
• Diagnosis of bulimia and/or anorexia nervosa in the last year
• Current or past use (with in past 12 months) of any medications containing NTX (e.g., Revia, Trexan), allergy to NTX
• Concomitant medications (e.g., monoamine oxidase inhibitors or benzodiazepines within past 14 days, antipsychotics, antidepressants, theophylline, systemic steroids, over-the-counter stimulants and anorectics)

Sponsors & Collaborators

• University of Pennsylvania: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Tobacco Use Research Center

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (2)

• 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. doi: 10.1038/sj.mp.4002002. No abstract available.

  PMID: 17592483 BACKGROUND

• Ray R, Jepson C, Patterson F, Strasser A, Rukstalis M, Perkins K, Lynch KG, O'Malley S, Berrettini WH, Lerman C. Association of OPRM1 A118G variant with the relative reinforcing value of nicotine. Psychopharmacology (Berl). 2006 Oct;188(3):355-63. doi: 10.1007/s00213-006-0504-2. Epub 2006 Sep 8.

  PMID: 16960700 RESULT

MeSH Terms

Conditions

Tobacco Use Disorder

Interventions

Naltrexone

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Naloxone; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Results Point of Contact

• Title: Caryn Lerman, Ph.D.
• Organization: University of Pennsylvania

clerman@mail.med.upenn.edu

215-746-7141

Study Officials

• Caryn Lerman, Ph.D.

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 23, 2005
• First Posted: December 26, 2005
• Study Start: March 1, 2004
• Primary Completion: October 1, 2005
• Study Completion: October 1, 2005
• Last Updated: December 10, 2013
• Results First Posted: December 10, 2013

Record last verified: 2013-11

Locations

US (1)