Baclofen Effects in Cigarette Smokers (BAC)

Baclofen Effects on Brain and Behavior in Cigarette Smokers

The proposed project will utilize perfusion functional magnetic resonance imaging (fMRI), a functional candidate gene association approach (of dopaminergic addictions-targeted polymorphisms), and the dopamine-modulating and gamma-aminobutyric acid (GABA) B receptor agonist, baclofen, to examine the brain and behavioral responses in smokers to appetitive smoking reminders (cues that motivate continued smoking and relapse). These studies will provide a means to identify an appetitive cue-sensitive pharmacologic-responsive endophenotype. Once brain/behavioral/genetic endophenotypes can be determined prior to treatment, smoking cessation treatments can be structured to meet individual needs, which will significantly improve treatment outcome.

Study Overview

• Status: Completed
• Conditions: Nicotine Dependence
• Intervention / Treatment: Drug: placebo; Drug: Baclofen

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania Center for Studies of Addiction

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Physically healthy, as determined by a comprehensive physical examination and approval of the study physician males or females who smoke cigarettes, ages 18-60.
• Smoke ≥ 6 cigarettes per day for at least 6 months prior to study start date.
• Females must be non-pregnant, non-lactating and either be of non-childbearing potential (i.e. sterilized via hysterectomy or bilateral tubal ligation or at least 1 year post-menopausal) or of child bearing potential but practicing a medically acceptable method of birth control. Examples of medically acceptable methods for this protocol include barrier (diaphragm or condom) with spermicide, an intrauterine device (IUD), the Nuvaring, oral contraceptives, levonorgestrel implant, hormonal injection or complete abstinence.
• Provide voluntary informed consent.
• Must be able to read. [Subjects are required to be able to read because there are several self-administered measures that they must read, understand and provide written answers.]
• Intelligence quotient of ≥ 80.

Exclusion Criteria:

• History of head trauma or injury causing loss of consciousness, lasting more than five (5) minutes or associated with skull fracture or inter-cranial bleeding or abnormal MRI.
• Current Diagnostic and Statistical Manual-IV (DSM-IV) Axis I diagnoses other than nicotine dependence.
• Presence of magnetically active irremovable prosthetics, plates, pins, permanent retainer, bullets, etc. (unless a radiologist confirms that it's presence is unproblematic). An x-ray may be obtained to determine eligibility given the possibility of a foreign body.
• History of psychosis.
• Claustrophobia or other medical condition preventing subject from lying in the MRI for approximately one (1) hour.
• Current diagnosis of or treatment within the last 3 months for alcohol dependence.
• Current use of any smoking cessation treatments such as Zyban, Chantix, Wellbutrin, patch, gum, inhaler, electronic cigarettes, herbal preparations.
• Vision problems that cannot be corrected with glasses.
• Weight exceeding 300 pounds [Imaging data acquisition is impaired with high weight individuals].
• History of stroke.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Sugar pill; Placebo-treated subjects will follow the identical schedule as Baclofen subjects.	Drug: placebo
Active Comparator: Baclofen; Baclofen will be dispensed in pill form. Baclofen will be prescribed at 20 mg 4 times per day. Each baclofen pill will be 10 mg. Thus, 2 pills will be taken at each scheduled dose for a total of 8 pills a day over a period of 8 weeks. In this way, the titration schedule, taper and potential dose reductions can be managed.	Drug: Baclofen; Other Names: Lioresal; Gablofen; Kemstro; Liofen; Beklo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cigarettes Smoked Per Day	Cigarettes per day at Scan Day 2; Baclofen group vs. placebo group	3 weeks (Scan Day 1, week1- Scan Day 2, week 4)

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Collaborators: National Institute on Drug Abuse (NIDA); National Institutes of Health (NIH)
• Investigators: Principal Investigator: Teresa R Franklin, Ph.D., University of Pennsylvania

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (Actual): June 1, 2017
• Study Completion (Actual): June 1, 2017

Study Registration Dates

• First Submitted: March 21, 2013
• First Submitted That Met QC Criteria: March 29, 2013
• First Posted (Estimate): April 1, 2013

Study Record Updates

• Last Update Posted (Actual): December 19, 2018
• Last Update Submitted That Met QC Criteria: November 30, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: fMRI; Baclofen; Nicotine Addiction
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Tobacco Use Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; GABA Agents; Neuromuscular Agents; Muscle Relaxants, Central; GABA Agonists; GABA-B Receptor Agonists; Baclofen
• Other Study ID Numbers: 817101; R01DA030394-01A1 (U.S. NIH Grant/Contract); PA Depart of Health (Other Grant/Funding Number: CURE (Commonwealth Universal Research Enhancement) Program)