Nicotine DependencePhase 2NCT01876810
Initial Screening of Gemfibrozil as a Novel Treatment for Tobacco Addiction
A Phase 2 study testing Gemfibrozil in people with Nicotine Dependence, run by Centre for Addiction and Mental Health at 2 sites in Canada.
Trial summary
The purpose of this study is to investigate the effect of gemfibrozil on nicotine reinforcement and cue-elicited craving. Other objectives of this study include screening for the ability of gemfibrozil to aid smoking abstinence during a brief quit attempt and examining the validity of using laboratory measures of… Read more about this study
- Who is it for?
- Ages 19 to 65 years
- Conditions the study is for
- Nicotine Dependence
- What is being tested?
- Gemfibrozil
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 28 participants
- Where
- 2 sitesCanada
- Study dates
- Feb 2014to Feb 2016
- 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 19 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 19-65 year old males and females
- smoking at least 10 cigarettes per day for at least 2 years
- intend to quit smoking within the next 3 months
- medically and psychologically healthy as determined by screening criteria
Who cannot join
- currently attempting to quit smoking
- treatment for tobacco addiction in the past 3 months
- use of nicotine replacement products, bupropion, or varenicline in the past 3 months as an aid to quit or reduce smoking
- use of any oral tobacco product in the past 3 months
- history of drug or alcohol dependence within last 5 years
- consumption of more than 15 alcoholic drinks per week on average during the past month
Show all 14Show fewer
- use of any illicit drug more than once per week on average during the past month
- current use of gemfibrozil or other fibrate medication
- current use of any medication that is contraindicated for gemfibrozil or that would interfere with the protocol in the opinion of MAI/QI. This includes, but is not limited to, anticoagulants, statins, other fibrates, other lipid-lowering agents such as niacin or herbal remedies, and any oral or injected medications for diabetes.
- any pre-existing gall-bladder disease or operation in the past 12 months
- any history of or current cardiovascular, liver, hepatic or renal disease
- diabetes
- pregnant, nursing, or become pregnant during the study
- use of psychoactive drugs or medications as revealed by urine toxicology
Trial locations and contacts
2 sites in 1 country.
Canada2 sites
Centre for Addiction and Mental Health
Toronto, Ontario, M5S 1S8
Centre of Addiction and Mental Health
Toronto, Ontario, M5S 2S1
About this study
Official title: Testing the PPAR Hypothesis of Nicotine Dependence in Humans: Gemfibrozil as a Novel Treatment for Tobacco Addiction
The purpose of this study is to investigate the effect of gemfibrozil on nicotine reinforcement and cue-elicited craving. Other objectives of this study include screening for the ability of gemfibrozil to aid smoking abstinence during a brief quit attempt and examining the validity of using laboratory measures of tobacco dependence to predict smoking abstinence. It is hypothesized that gemfibrozil will result in diminished nicotine reinforcement, an attenuated response to smoking cues, and an increase in smoking abstinence compared with placebo. It is also hypothesized that the laboratory measures will prove valid in predicting abstinence.
Read the detailed description
Animal studies have shown that drugs acting as agonists at alpha-type peroxisome proliferator-activated receptors (PPARα) suppress nicotine self-administration, attenuate relapse to nicotine-seeking behavior in the reinstatement model, and block nicotine-induced neuronal firing and dopamine release in reward pathways of the brain. These results have been demonstrated with synthetic PPARα agonists and with fibrate drugs (clofibrate, fenofibrate), which are used clinically to treat elevated cholesterol and triglycerides levels. Thus, PPARα is a potential target for the treatment of tobacco addiction. This is the first human study to investigate whether a fibrate drug (gemfibrozil, Lopid®) can reduce nicotine reward and aid smokers in becoming tobacco abstinent.
The objectives of this study are:
- to investigate the effect of gemfibrozil on laboratory measures of nicotine reinforcement and cue-elicited craving
- to screen for the ability of gemfibrozil to aid smoking abstinence during a brief quit attempt
- to examine the validity of using laboratory measures of tobacco dependence to predict smoking abstinence and possible gemfibrozil-related increases in smoking abstinence
This outpatient study will be conducted at the Center for Addiction and Mental Health (CAMH) in Toronto, Canada. This site will enroll 40 adult smokers who intend to quit smoking in the next 3 months.
The study is a double-blind, placebo-controlled, crossover design comparing the effects of gemfibrozil and placebo. The study will comprise two 2-week medication phases with a washout period of at least one week. At the end of the first medication week laboratory measures will be taken and during the second medication week participants will make a quit attempt and abstinence will be assessed.
Outcome measures include laboratory assessments of nicotine reinforcement and smoking cue reactivity. The measure of nicotine reinforcement is the percentage of nicotine cigarette puffs chosen during a forced-choice task. Measures of cue reactivity include tobacco craving, mood, and autonomic responsivity. Other measures are days of smoking abstinence during the quit-attempt weeks. Abstinence is assessed by self-reports of no smoking and by breath carbon monoxide < 5 ppm on clinic visits. Other assessments of abstinence include self-reported tobacco craving and withdrawal.
- Conditions
- Nicotine Dependence
- Being tested
- Gemfibrozil, Placebo
- Keywords
- Gemfibrozil, Nicotine Dependence, Smoking, Cigarettes
- Medical subject headings
- Tobacco Use Disorder, Smoking
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GemfibrozilDrug
Also called Lopid
600 mg of gemfibrozil (one capsule) twice daily for two weeks.
PlaceboDrug
Also called Lactose
One lactose pill twice a day for two weeks.
| Study group | Role | What they receive |
|---|---|---|
| Gemfibrozil | Experimental | 600 mg of gemfibrozil (one capsule) twice daily for two weeks. Receives: Drug: Gemfibrozil |
| Placebo pill | Placebo comparator | One lactose pill twice a day for two weeks. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Days With Self-report of No Smoking and Breath Carbon Monoxide of <5 PPM During Quit-attempt Weeks
the number of days of no smoking was calculated for each participant. Abstinence was verified by daily Self-reports of no smoking and breath carbon monoxide < 5 ppm
Measured: 1 week in each phase
Secondary outcomes (1)
The Percentage of Choice of Nicotinized Cigarettes After 1 Week of Treatment
Percentage of choice of Nicotinized cigarettes was calculated for each participant during the lab session which took place after 1 week of treatment.
Each session started with participants taking four puffs of their preferred-brand cigarette to standardize the time from last nicotine exposure. Participants were asked to complete some questionnaires at baseline. Then, they were asked to relax for 30 min listening to music or reading. Four exposure trials followed that were separated by 30 min of relaxation. In each exposure trial, participants took four puffs of a Nicotinized (A) or Denicotinized (less than 0.05 mg nicotine.) (B) cigarette in the order of ABAB or BABA. Cigarettes were color-coded. Participants then began four choice trials separated by 30 min of relaxation. In each trial, participants chose any combination of 4 puffs from the two cigarettes.
Measured: during the lab forced choice paradigm after 1 week of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jun 2013 (estimated)
- Study startFeb 2014
- Primary completionFeb 2016
- Study completionFeb 2016
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.
- Other trials for Nicotine DependenceStudies of the same condition, open and under way.
- More trials run by Centre for Addiction and Mental HealthThe 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre for Addiction and Mental Health
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Bernard Le Foll, Centre for Addiction and Mental Health
- Investigators
- Bernard Le Foll, MD, PhD, Principal investigator, Centre for Addiction and Mental Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01876810
- Sponsor's protocol ID
- 082/2012
- Status last verified
- Apr 2017
- First submitted
- 6 Jun 2013
- Last updated
- 20 Apr 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Testing the PPAR Hypothesis of Nicotine Dependence in Humans: Gemfibrozil as a Novel Treatment for Tobacco Addiction
- ClinicalTrials.gov ID
- NCT01876810
- Acronym / sponsor ID
- 082/2012
- Conditions
- Nicotine Dependence
- Keywords
- Gemfibrozil, Nicotine Dependence, Smoking, Cigarettes
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Centre for Addiction and Mental HealthUniversity, hospital or other
- Study start
- Feb 2014
- Primary completion
- Feb 2016 (actual)
- Study completion
- Feb 2016 (actual)
- First posted
- 13 Jun 2013 (estimated)
- Results
- Posted 20 Apr 2017
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 investigate the effect of gemfibrozil on nicotine reinforcement and cue-elicited craving. Other objectives of this study include screening for the ability of gemfibrozil to aid smoking abstinence during a brief quit attempt and examining the validity of using laboratory measures of tobacco dependence to predict smoking abstinence. It is hypothesized that gemfibrozil will result in diminished nicotine reinforcement, an attenuated response to smoking cues, and an increase in smoking abstinence compared with placebo. It is also hypothesized that the laboratory measures will prove valid in predicting abstinence.
Detailed description
Animal studies have shown that drugs acting as agonists at alpha-type peroxisome proliferator-activated receptors (PPARα) suppress nicotine self-administration, attenuate relapse to nicotine-seeking behavior in the reinstatement model, and block nicotine-induced neuronal firing and dopamine release in reward pathways of the brain. These results have been demonstrated with synthetic PPARα agonists and with fibrate drugs (clofibrate, fenofibrate), which are used clinically to treat elevated cholesterol and triglycerides levels. Thus, PPARα is a potential target for the treatment of tobacco addiction. This is the first human study to investigate whether a fibrate drug (gemfibrozil, Lopid®) can reduce nicotine reward and aid smokers in becoming tobacco abstinent.
The objectives of this study are:
- to investigate the effect of gemfibrozil on laboratory measures of nicotine reinforcement and cue-elicited craving
- to screen for the ability of gemfibrozil to aid smoking abstinence during a brief quit attempt
- to examine the validity of using laboratory measures of tobacco dependence to predict smoking abstinence and possible gemfibrozil-related increases in smoking abstinence
This outpatient study will be conducted at the Center for Addiction and Mental Health (CAMH) in Toronto, Canada. This site will enroll 40 adult smokers who intend to quit smoking in the next 3 months.
The study is a double-blind, placebo-controlled, crossover design comparing the effects of gemfibrozil and placebo. The study will comprise two 2-week medication phases with a washout period of at least one week. At the end of the first medication week laboratory measures will be taken and during the second medication week participants will make a quit attempt and abstinence will be assessed.
Outcome measures include laboratory assessments of nicotine reinforcement and smoking cue reactivity. The measure of nicotine reinforcement is the percentage of nicotine cigarette puffs chosen during a forced-choice task. Measures of cue reactivity include tobacco craving, mood, and autonomic responsivity. Other measures are days of smoking abstinence during the quit-attempt weeks. Abstinence is assessed by self-reports of no smoking and by breath carbon monoxide < 5 ppm on clinic visits. Other assessments of abstinence include self-reported tobacco craving and withdrawal.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Gemfibrozil | Experimental | Drug: Gemfibrozil600 mg of gemfibrozil (one capsule) twice daily for two weeks. |
| Placebo pill | Placebo comparator | Drug: PlaceboOne lactose pill twice a day for two weeks. |
Who may qualify
- Ages
- 19 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 19-65 year old males and females
- smoking at least 10 cigarettes per day for at least 2 years
- intend to quit smoking within the next 3 months
- medically and psychologically healthy as determined by screening criteria
Key exclusion criteria (14 listed)
- currently attempting to quit smoking
- treatment for tobacco addiction in the past 3 months
- use of nicotine replacement products, bupropion, or varenicline in the past 3 months as an aid to quit or reduce smoking
- use of any oral tobacco product in the past 3 months
- history of drug or alcohol dependence within last 5 years
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 |
|---|---|---|
| GemfibrozilAlso: Lopid600 mg of gemfibrozil (one capsule) twice daily for two weeks. | Drug | Gemfibrozil |
| PlaceboAlso: LactoseOne lactose pill twice a day for two weeks. | Drug | Placebo pill |
Primary outcome
Number of Days With Self-report of No Smoking and Breath Carbon Monoxide of <5 PPM During Quit-attempt Weeks
Time frame: 1 week in each phase
the number of days of no smoking was calculated for each participant. Abstinence was verified by daily Self-reports of no smoking and breath carbon monoxide < 5 ppm
1 secondary outcome
The Percentage of Choice of Nicotinized Cigarettes After 1 Week of Treatment
Time frame: during the lab forced choice paradigm after 1 week of treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Apr 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Information about research at the Centre for Addiction and Mental Health, Canada's largest mental health and addiction teachingLink provided by the sponsor.
- Individual participant dataSharing planned: Yes
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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.
Bernard Le Foll, MD, PhD principal investigator
Centre for Addiction and Mental Health
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Gemfibrozil in people with Nicotine Dependence, run by Centre for Addiction and Mental Health at 2 sites in Canada.
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 14 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 20 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. 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 20 Apr 2017). 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 Days With Self-report of No Smoking and Breath Carbon Monoxide of <5 PPM During Quit-attempt Weeks (time frame: 1 week in each phase). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 20 Apr 2017.