Initial Screening of Gemfibrozil as a Novel Treatment for Tobacco Addiction

NCT ID: NCT01876810

Last Updated: 2017-04-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-02-28
• Study Completion Date: 2016-02-29

Brief 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 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:

1. to investigate the effect of gemfibrozil on laboratory measures of nicotine reinforcement and cue-elicited craving

2. to screen for the ability of gemfibrozil to aid smoking abstinence during a brief quit attempt

3. 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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Gemfibrozil

600 mg of gemfibrozil (one capsule) twice daily for two weeks.

Group Type: EXPERIMENTAL

Gemfibrozil

Intervention Type: DRUG

600 mg of gemfibrozil (one capsule) twice daily for two weeks.

Placebo pill

One lactose pill twice a day for two weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

One lactose pill twice a day for two weeks.

Interventions

Gemfibrozil

600 mg of gemfibrozil (one capsule) twice daily for two weeks.

Intervention Type: DRUG

Placebo

One lactose pill twice a day for two weeks.

Intervention Type: DRUG

Other Intervention Names

Lopid; Lactose

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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
• 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

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centre for Addiction and Mental Health

OTHER

Sponsor Role: lead

Responsible Party

Bernard Le Foll

Scientist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Bernard Le Foll, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Centre for Addiction and Mental Health

Locations

Centre for Addiction and Mental Health

Toronto, Ontario, Canada

Centre of Addiction and Mental Health

Toronto, Ontario, Canada

Countries

Canada

Related Links

http://www.camh.net/research

Information about research at the Centre for Addiction and Mental Health, Canada's largest mental health and addiction teaching

Other Identifiers

082/2012

Identifier Type: -

Identifier Source: org_study_id

NCT01900145

Identifier Type: -

Identifier Source: nct_alias