Tobacco DependencePhase 2NCT00270231

Effects of Naltrexone on Nicotine Reinforcement

A Phase 2 study testing Naltrexone in people with Tobacco Dependence, run by University of Pennsylvania at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Tobacco Dependence
What is being tested?: Naltrexone
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 64 participants
Where: 1 siteUnited States
Study dates: Mar 2004to Oct 2005
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 18 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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)

Show all 9Show fewer

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)

Trial locations and contacts

1 site in 1 country.

United States1 site

Tobacco Use Research Center
Philadelphia, Pennsylvania, 19104

Other trials in United States

About this study

Official title: Pharmacogenetic Investigation of Naltrexone

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.

Read the 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.

Conditions: Tobacco Dependence
Being tested: Naltrexone, Placebo
Keywords: within-subjects, crossover, laboratory study, Naltrexone vs. Placebo
Medical subject headings: Tobacco Use Disorder

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

NaltrexoneDrug
Also called Revia or Trexan
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.
PlaceboDrug
Also called Sugar pill; inactive medication
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.

Study groups in NCT00270231
Study group	Role	What they receive
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. Receives: 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. Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 2 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Mar 2004Oct 2005

First posted26 Dec 2005 (estimated)
Study startMar 2004
Primary completionOct 2005
Study completionOct 2005

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 (2)Papers the sponsor has linked to this study.
Other trials for Tobacco DependenceStudies of the same condition, open and under way.
More trials run by University of PennsylvaniaThe sponsor's other registered studies.
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
Allocation: Randomised
Intervention model: Crossover
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 64 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00270231
Sponsor's protocol ID: 800810
Other IDs: R01DA017555
Status last verified: Nov 2013
First submitted: 23 Dec 2005
Last updated: 10 Dec 2013
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

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. doi: 10.1038/sj.mp.4002002. No abstract available.
PubMed 17592483
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.
PubMed 16960700

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Effectiveness of Volitional Help Sheets as an Adjunct to Treatment to Promote Behavior Change: A Pilot Study on Smoking
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Young Adult Tobacco/Nicotine and Cannabis Co-use
Tobacco Use Disorder, Nicotine Dependence
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The INITIATE Study: Initiating Nicotine Dependence Treatment for Smokers Admitted to Emergency Departments
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All Tobacco Dependence trials

Study at a glance

From the registry record, last updated by the sponsor on 10 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Pharmacogenetic Investigation of Naltrexone
ClinicalTrials.gov ID: NCT00270231
Acronym / sponsor ID: 800810
Conditions: Tobacco Dependence
Keywords: within-subjects, crossover, laboratory study, Naltrexone vs. Placebo
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 64 participants (actual)
Lead sponsor: University of PennsylvaniaUniversity, hospital or other
Collaborators: National Institute on Drug Abuse (NIDA)
Study start: Mar 2004
Primary completion: Oct 2005 (actual)
Study completion: Oct 2005 (actual)
First posted: 26 Dec 2005 (estimated)
Results: Posted 10 Dec 2013

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Allocation: Randomised
Intervention model: Crossover
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 2

Arm	Type	Receives
Naltrexone	Active comparator	Drug: NaltrexoneAll 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.
Placebo	Placebo comparator	Drug: PlaceboAll 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.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

Participants must be greater than or equal to 18 years
Based on the medical history, physical and laboratory examination, female subjects must:
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.

Key exclusion criteria (9 listed)

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).

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
NaltrexoneAlso: Revia or TrexanAll 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
PlaceboAlso: Sugar pill; inactive medicationAll 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

Primary outcome

Number of Nicotine Cigarette Choices Taken During the Cigarette Choice Procedure.
Time frame: 2 hours
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.

Results and safety

Results posted to the registry on 10 Dec 2013, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Naltrexone, Then Placebo	32	31
Placebo, Then Naltrexone	32	31

Primary outcome: Number of Nicotine Cigarette Choices Taken During the Cigarette Choice Procedure.

Time frame: 2 hours. Mean (Standard Deviation). Unit: Number of Nicotine Cigarette Puffs Taken

Measure	OPRM1 Genotype - A/A n = 30	OPRM1 Genotype - A/G or G/G n = 30
Value	18.5 (4.2)	16.2 (6.2)

Population analysed: Participants were analyzed with respect to genotype regardless of intervention.

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Naltrexone Only	0 of 64 (0%)	0 of 64 (0%)	Not reported
Placebo Only	0 of 64 (0%)	0 of 64 (0%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 Dec 2013.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 17592483Ray 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.
Results publication: PubMed 16960700Ray 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.

Related trials for Tobacco Dependence

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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.

Caryn Lerman, Ph.D. principal investigator

University of Pennsylvania

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 Naltrexone in people with Tobacco Dependence, run by University of Pennsylvania 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 9 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 10 Dec 2013. 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 10 Dec 2013). 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?

Number of Nicotine Cigarette Choices Taken During the Cigarette Choice Procedure. (time frame: 2 hours). 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 NCT00270231, which also lists 2 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 10 Dec 2013.