Initial Screening of Gemfibrozil as a Novel Treatment for Tobacco Addiction

Nicotine Dependence Clinical Trial

Official title:

Testing the PPAR Hypothesis of Nicotine Dependence in Humans: Gemfibrozil as a Novel Treatment for Tobacco Addiction

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01876810
• Other study ID #: 082/2012
• Status: Completed
• Phase: Phase 2
• First received: June 6, 2013
• Last updated: April 18, 2017
• Start date: February 2014
• Est. completion date: February 2016

Study information

• Verified date: April 2017
• Source: Centre for Addiction and Mental Health
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 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.

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.

Other known NCT identifiers

• NCT01900145

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: February 2016
• Est. primary completion date: February 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Nicotine Dependence
• Tobacco Use Disorder

Intervention

Drug:
• Gemfibrozil
600 mg of gemfibrozil (one capsule) twice daily for two weeks.
• Placebo
One lactose pill twice a day for two weeks.

Locations

Country	Name	City	State
Canada	Centre for Addiction and Mental Health	Toronto	Ontario
Canada	Centre of Addiction and Mental Health	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Centre for Addiction and Mental Health

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Cue- Reactivity Visual Analogue Scale for Craving After 1 Week of Treatment	In this study, each session started with participants taking four puffs of their preferred-brand cigarette to standardize the time from last nicotine exposure. Participants were then seated in a comfortable chair and completed the baseline Visual Analogue Scale for craving 0-100 mm (The higher the number the more is the craving). The smoking cue was a pack of cigarettes and a lighter. Participants were instructed to light the cigarette without puffing and hold it for 30 sec while the physiological recordings were measured. Then the participant was asked to extinguish the cigarette. The neutral cue was an unsharpened pencil, a notepad, and a sharpener. Participants were instructed to sharpen the pencil and hold it as if writing for 30 sec. Participants completed the Visual Analogue Scale for craving during the cue, and 15 and 30 min after cue presentation.	during the lab Cue- reactivity paradigm after 1 week of treatment
Primary	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	1 week in each phase
Secondary	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.	during the lab forced choice paradigm after 1 week of treatment

External Links

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