SmokingPhase 1/2NCT00502216
Naltrexone and Varenicline: Weight Gain and Tolerability in Cigarette Smokers
A Phase 1/2 study testing Naltrexone and Varenicline in people with Smoking and Nicotine Dependence, run by Yale University at 1 site in United States.
Trial summary
The purpose of this study is to determine whether the combination of naltrexone (Depade) and varenicline (Chantix) minimizes post-smoking cessation weight gain and how well the combination is tolerated. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Smoking, Nicotine Dependence
- What is being tested?
- Naltrexone and Varenicline
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2007to Jun 2009
- Phase
- Phase 1/2
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Between the ages of 18 and 75
- Smoking 10 or more cigarettes per day
- Fewer than 3 months of smoking abstinence in the past year
- Motivated to stop smoking
Who cannot join
- Current use of opiates, and/or a urine toxicology screen positive for opiates
- Chronic pain conditions necessitating opioid treatment (naltrexone, an opioid antagonist will make these medications ineffective)
- Evidence of significant hepatocellular injury as evidence by AST or ALT >3 x normal or elevated bilirubin
- History of cirrhosis
- Any serious or unstable disease within 6 months
- Seizure risk
Show all 24Show fewer
- Diabetes mellitus requiring insulin or oral hypoglycemic medications
- Hepatic or renal impairment
- Use of a monoamine oxidase inhibitor in the prior 14 days
- Clinically significant cardiovascular disease within 6 months
- Uncontrolled hypertension
- Baseline systolic blood pressure higher than 150 mm Hg or diastolic blood pressure higher than 95 mm Hg
- Severe chronic obstructive pulmonary disease
- History of cancer (except treated basal cell or squamous cell carcinoma of the skin)
- History of clinically significant allergic reactions
- Major depressive disorder within the past year requiring treatment
- History of or current panic disorder, psychosis, bipolar disorder, or eating disorders
- Alcohol or drug abuse/dependency within the past year
- Use of another investigational drug within 30 days
- Intention to donate blood or blood products during the treatment phase of the study
- Use of tobacco products other than cigarettes or use of marijuana
- Use of nicotine replacement therapy, clonidine, varenicline, bupropion, or nortriptyline within the month prior to enrollment or intention to use medication that might interfere with study medication
- Body Mass Index (calculated as weight in kilograms divided by the square of height in meters) less than 15 or greater than 38 or weight less than 45 kg.
- Females of childbearing potential who are pregnant, nursing, or not practicing effective contraception (oral injectable, or implantable contraceptives, intrauterine device, or barrier method with spermacide)
Trial locations and contacts
1 site in 1 country.
United States1 site
Yale University School of Medicine Substance Abuse Treatment Unit
New Haven, Connecticut, 06511
About this study
Official title: Naltrexone and Varenicline: Weight Gain and Tolerability in Smokers
The purpose of this study is to determine whether the combination of naltrexone (Depade) and varenicline (Chantix) minimizes post-smoking cessation weight gain and how well the combination is tolerated.
Read the detailed description
Varenicline, a medication recently approved by the FDA, results in smoking cessation rates as high as 50%, significantly better than bupropion or placebo. However, varenicline does not reduce post-cessation weight gain, so weight concerns may keep some smokers from taking advantage of this effective therapy.
A potential solution would be to combine varenicline with an agent that reduces weight gain. In this regard, several studies have shown that naltrexone reduces weight gain (O'Malley et al., 2006; Toll et al., 2007).
This effect appears to be dose dependent, favoring lower doses (i.e., 25 mg daily). Thus, the proposed study seeks to conduct a pilot clinical trial of low dose naltrexone (25 mg daily) compared to placebo for minimizing weight gain in combination with varenicline for smoking cessation. Forty individuals who smoke at least 10 cigarettes per day will receive open-label varenicline for 12 weeks according to the recommended titration schedule up to 1 mg varenicline twice daily. Subjects will be randomized to receive either placebo or 25 mg naltrexone daily, with treatment starting at the quit date (after 1 week on varenicline to minimize nausea, a side effect of both varenicline and naltrexone) and continuing for 11 weeks. Subjects will take 12.5 mg naltrexone daily for the first week and 25 mg naltrexone daily for the next 10 weeks of treatment. In an effort to uncover mechanisms for naltrexone's weight suppressant effects, an experiment will be conducted using food odors and food consumption to examine naltrexone's effects on palatability, incentive value, and alliesthesia.
This experiment will be conducted pretreatment and after 2 weeks on naltrexone. The primary aim of this pilot study is to examine weight gain in participants who complete the clinical trial treatment. Weight gain for those who are continuously abstinent for the last 4 weeks of treatment and rates of adverse events will be secondary outcomes. The effects of naltrexone on odor/food palatability, incentive value, and alliesthesia will be exploratory outcomes. Effect size estimates for weight gain will be generated for a NIH grant application.
- Conditions
- Smoking, Nicotine Dependence
- Being tested
- Naltrexone, Varenicline
- Keywords
- Tobacco, Smoking, Weight, Naltrexone, Varenicline
- Medical subject headings
- Smoking, Tobacco Use Disorder, Body Weight
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NaltrexoneDrug
Varenicline (Chantix) 1 mg oral tablet twice per day + naltrexone 25 mg oral capsule once per day
VareniclineDrug
Also called Chantix
Arm 1 (Experimental) = Varenicline (Chantix) 1 mg oral tablet twice per day + naltrexone 25 mg oral capsule once per day; Arm 2 (Placebo Comparator) = Varenicline (Chantix) 1 mg oral tablet twice per day + placebo naltrexone 25 mg oral capsule once per day
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Arm 1 (Experimental) = Varenicline (Chantix) 1 mg oral tablet twice per day + naltrexone 25 mg oral capsule once per day Receives: Drug: Naltrexone; Drug: Varenicline |
| 2 | Placebo comparator | Arm 2 (Placebo Comparator) = Varenicline (Chantix) 1 mg oral tablet twice per day + placebo naltrexone 25 mg oral capsule once per day Receives: Drug: Varenicline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Weight Gain in Treatment Completers
Measured: baseline and 12 weeks
Secondary outcomes (2)
Weight Gain in Participants Who Are Continuously Abstinent for the Last 4 Weeks of Treatment
Measured: 4 weeks
Tolerability of the Combination of 25 mg Naltrexone and 2 mg Varenicline
Tolerability was measured by tracking adverse events. These data are reported in detail in the adverse events section. Presented are an unduplicated count of participants that experienced at least 1 adverse event.
Measured: 11 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2007 (estimated)
- Study startJul 2007
- Primary completionJun 2009
- Study completionJun 2009
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 (1)Papers the sponsor has linked to this study.
- Other trials for SmokingStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institute on Drug Abuse (NIDA)
- Responsible party
- Sponsor
- Investigators
- Benjamin A. Toll, PhD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00502216
- Sponsor's protocol ID
- 0704002538
- Other IDs
- P50AA015632, NIH Grant P50-AA15632, NIH Grant K12-DA00167
- Status last verified
- Jan 2018
- First submitted
- 13 Jul 2007
- Last updated
- 17 Jan 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Livingstone-Banks J, Fanshawe TR, Thomas KH, Theodoulou A, Hajizadeh A, Hartman L, Lindson N. Nicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev. 2023 May 5;5(5):CD006103. doi: 10.1002/14651858.CD006103.pub8.
PubMed 37142273
Study at a glance
From the registry record, last updated by the sponsor on 17 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Naltrexone and Varenicline: Weight Gain and Tolerability in Smokers
- ClinicalTrials.gov ID
- NCT00502216
- Acronym / sponsor ID
- 0704002538
- Conditions
- Smoking, Nicotine Dependence
- Keywords
- Tobacco, Smoking, Weight, Naltrexone, Varenicline
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institute on Drug Abuse (NIDA)
- Study start
- Jul 2007
- Primary completion
- Jun 2009 (actual)
- Study completion
- Jun 2009 (actual)
- First posted
- 17 Jul 2007 (estimated)
- Results
- Posted 21 Sep 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether the combination of naltrexone (Depade) and varenicline (Chantix) minimizes post-smoking cessation weight gain and how well the combination is tolerated.
Detailed description
Varenicline, a medication recently approved by the FDA, results in smoking cessation rates as high as 50%, significantly better than bupropion or placebo. However, varenicline does not reduce post-cessation weight gain, so weight concerns may keep some smokers from taking advantage of this effective therapy.
A potential solution would be to combine varenicline with an agent that reduces weight gain. In this regard, several studies have shown that naltrexone reduces weight gain (O'Malley et al., 2006; Toll et al., 2007).
This effect appears to be dose dependent, favoring lower doses (i.e., 25 mg daily). Thus, the proposed study seeks to conduct a pilot clinical trial of low dose naltrexone (25 mg daily) compared to placebo for minimizing weight gain in combination with varenicline for smoking cessation. Forty individuals who smoke at least 10 cigarettes per day will receive open-label varenicline for 12 weeks according to the recommended titration schedule up to 1 mg varenicline twice daily. Subjects will be randomized to receive either placebo or 25 mg naltrexone daily, with treatment starting at the quit date (after 1 week on varenicline to minimize nausea, a side effect of both varenicline and naltrexone) and continuing for 11 weeks. Subjects will take 12.5 mg naltrexone daily for the first week and 25 mg naltrexone daily for the next 10 weeks of treatment. In an effort to uncover mechanisms for naltrexone's weight suppressant effects, an experiment will be conducted using food odors and food consumption to examine naltrexone's effects on palatability, incentive value, and alliesthesia.
This experiment will be conducted pretreatment and after 2 weeks on naltrexone. The primary aim of this pilot study is to examine weight gain in participants who complete the clinical trial treatment. Weight gain for those who are continuously abstinent for the last 4 weeks of treatment and rates of adverse events will be secondary outcomes. The effects of naltrexone on odor/food palatability, incentive value, and alliesthesia will be exploratory outcomes. Effect size estimates for weight gain will be generated for a NIH grant application.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Naltrexone, Drug: VareniclineArm 1 (Experimental) = Varenicline (Chantix) 1 mg oral tablet twice per day + naltrexone 25 mg oral capsule once per day |
| 2 | Placebo comparator | Drug: VareniclineArm 2 (Placebo Comparator) = Varenicline (Chantix) 1 mg oral tablet twice per day + placebo naltrexone 25 mg oral capsule once per day |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Between the ages of 18 and 75
- Smoking 10 or more cigarettes per day
- Fewer than 3 months of smoking abstinence in the past year
- Motivated to stop smoking
Key exclusion criteria (24 listed)
- Current use of opiates, and/or a urine toxicology screen positive for opiates
- Chronic pain conditions necessitating opioid treatment (naltrexone, an opioid antagonist will make these medications ineffective)
- Evidence of significant hepatocellular injury as evidence by AST or ALT >3 x normal or elevated bilirubin
- History of cirrhosis
- Any serious or unstable disease within 6 months
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 |
|---|---|---|
| NaltrexoneVarenicline (Chantix) 1 mg oral tablet twice per day + naltrexone 25 mg oral capsule once per day | Drug | 1 |
| VareniclineAlso: ChantixArm 1 (Experimental) = Varenicline (Chantix) 1 mg oral tablet twice per day + naltrexone 25 mg oral capsule once per day; Arm 2 (Placebo Comparator) = Varenicline (Chantix) 1 mg oral tablet twice per day + placebo naltrexone 25 mg oral capsule once per day | Drug | 1, 2 |
Primary outcome
Weight Gain in Treatment Completers
Time frame: baseline and 12 weeks
2 secondary outcomes
Weight Gain in Participants Who Are Continuously Abstinent for the Last 4 Weeks of Treatment
Time frame: 4 weeks
Tolerability of the Combination of 25 mg Naltrexone and 2 mg Varenicline
Time frame: 11 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jan 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37142273Livingstone-Banks J, Fanshawe TR, Thomas KH, Theodoulou A, Hajizadeh A, Hartman L, Lindson N. Nicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev. 2023 May 5;5(5):CD006103. doi: 10.1002/14651858.CD006103.pub8.
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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.
Benjamin A. Toll, PhD principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Naltrexone and Varenicline in people with Smoking and Nicotine Dependence, run by Yale University 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 4 inclusion and 24 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 17 Jan 2018. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 21 Sep 2010). 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?
Weight Gain in Treatment Completers (time frame: baseline and 12 weeks). 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 NCT00502216, which also lists 1 linked publication.
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 17 Jan 2018.