Initial Screening of Gemfibrozil as a Novel Treatment for Tobacco Addiction

This study is currently recruiting participants.
Verified April 2014 by Centre for Addiction and Mental Health
Sponsor:
Information provided by (Responsible Party):
Bernard Le Foll, Centre for Addiction and Mental Health
ClinicalTrials.gov Identifier:
NCT01876810
First received: June 6, 2013
Last updated: April 7, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Nicotine Dependence
Drug: Gemfibrozil
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Testing the PPAR Hypothesis of Nicotine Dependence in Humans: Gemfibrozil as a Novel Treatment for Tobacco Addiction

Resource links provided by NLM:


Further study details as provided by Centre for Addiction and Mental Health:

Primary Outcome Measures:
  • Nicotine Reinforcement and Smoking Cue Reactivity [ Time Frame: 1 week ] [ Designated as safety issue: No ]
    Percentage of nicotine cigarette puffs chosen during a forced-choice task and tobacco craving, mood, and autonomic responsivity.


Secondary Outcome Measures:
  • Smoking abstinence during quit-attempt weeks [ Time Frame: 1 week ] [ Designated as safety issue: No ]
    Self-reports of no smoking and breath carbon monoxide < 5 ppm. Also assessed by self-reported tobacco craving and withdrawal.


Estimated Enrollment: 40
Study Start Date: February 2014
Estimated Study Completion Date: August 2016
Estimated Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Gemfibrozil
600 mg of gemfibrozil (one capsule) twice daily for two weeks.
Drug: Gemfibrozil
600 mg of gemfibrozil (one capsule) twice daily for two weeks.
Other Name: Lopid
Placebo Comparator: Placebo pill
One lactose pill twice a day for two weeks.
Drug: Placebo
One lactose pill twice a day for two weeks.
Other Name: Lactose

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.

  Eligibility

Ages Eligible for Study:   19 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01876810

Contacts
Contact: Marie Gendy 416-535-8501 ext 36032 marie.gendy@camh.ca
Contact: Patricia DiCiano, PhD 416-535-8501 ext 34002 Patricia.DiCiano@camh.ca

Locations
Canada, Ontario
Centre for Addiction and Mental Health Recruiting
Toronto, Ontario, Canada, M5S 1S8
Principal Investigator: Bernard Le Foll, MD, PhD         
Centre of Addiction and Mental Health Recruiting
Toronto, Ontario, Canada, M5S 2S1
Contact: Marie Gendy    416-535-8501 ext 36032    marie.gendy@camh.ca   
Contact: Patricia DiCiano, PhD    416-535-8501 ext 34002    paricia.diciano@camh.ca   
Principal Investigator: Bernard LeFoll, MD/PhD         
Sponsors and Collaborators
Centre for Addiction and Mental Health
Investigators
Principal Investigator: Bernard Le Foll, MD, PhD Centre for Addiction and Mental Health
  More Information

Additional Information:
No publications provided

Responsible Party: Bernard Le Foll, Scientist, Centre for Addiction and Mental Health
ClinicalTrials.gov Identifier: NCT01876810     History of Changes
Obsolete Identifiers: NCT01900145
Other Study ID Numbers: 082_2012
Study First Received: June 6, 2013
Last Updated: April 7, 2014
Health Authority: Canada: Health Canada

Keywords provided by Centre for Addiction and Mental Health:
Gemfibrozil
Nicotine Dependence
Smoking
Cigarettes

Additional relevant MeSH terms:
Tobacco Use Disorder
Substance-Related Disorders
Mental Disorders
Gemfibrozil
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 21, 2014