BAC: Baclofen Effects in Cigarette Smokers

• Sponsor: University of Pennsylvania (Other)
• Overall Status: Completed
• CT.gov ID: NCT01821560
• Collaborator: National Institute on Drug Abuse (NIDA) (NIH), National Institutes of Health (NIH) (NIH)
• Enrollment: 44
• Location: 1
• Arms: 2
• Duration (Months): 51
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Nicotine Dependence	Drug: Baclofen; Drug: placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 44 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Baclofen Effects on Brain and Behavior in Cigarette Smokers
• Study Start Date: Mar 1, 2013
• Actual Primary Completion Date: Jun 1, 2017
• Actual Study Completion Date: Jun 1, 2017

Arms and Interventions

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: Kemstro Lioresal Liofen Gablofen Beklo

Outcome Measures

Primary Outcome Measures

1. Cigarettes Smoked Per Day [3 weeks (Scan Day 1, week1- Scan Day 2, week 4)]

   Cigarettes per day at Scan Day 2; Baclofen group vs. placebo group

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Pennsylvania Center for Studies of Addiction	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• University of Pennsylvania
• National Institute on Drug Abuse (NIDA)
• National Institutes of Health (NIH)

Investigators

• Principal Investigator: Teresa R Franklin, Ph.D., University of Pennsylvania

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 6, 2017

More Information

Publications

None provided.

• Responsible Party: University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT01821560
• Other Study ID Numbers: 817101; R01DA030394-01A1; PA Depart of Health
• First Posted: Apr 1, 2013
• Last Update Posted: Dec 19, 2018
• Last Verified: Nov 1, 2018

• Keywords provided by University of Pennsylvania: Nicotine Addiction; fMRI; Baclofen
• Additional relevant MeSH terms: Tobacco Use Disorder; Baclofen

Study Results

Participant Flow

Recruitment Details	Participants were recruitment between March 2013-March 2017 via word of mouth, flyers, an online study database managed by the University of Pennsylvania, and also social media advertisements (Facebook).
Pre-assignment Detail	Prior to study group assignments, all participants must first provide informed consent and then are found to be eligible to participate in the study after completing the screening process. The screening process included a full physical and psychological evaluation to ensure all participants are both physically and mentally healthy enough.

Arm/Group Title	Sugar Pill	Baclofen
Arm/Group Description	Placebo-treated subjects will follow the identical schedule as Baclofen subjects. placebo	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. Baclofen
Period Title: Overall Study
STARTED	22	22
COMPLETED	16	15
NOT COMPLETED	6	7

Baseline Characteristics

Arm/Group Title	Sugar Pill	Baclofen	Total
Arm/Group Description	Placebo-treated subjects will follow the identical schedule as Baclofen subjects. placebo	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. Baclofen	Total of all reporting groups
Overall Participants	22	22	44
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	40.2 (12.1)	38.9 (12.0)	39.5 (11.9)
Sex: Female, Male (Count of Participants)
Female	8 36.4%	8 36.4%	16 36.4%
Male	14 63.6%	14 63.6%	28 63.6%
Race/Ethnicity, Customized (Count of Participants)
African American	14 63.6%	12 54.5%	26 59.1%
White Non-Hispanic	3 13.6%	5 22.7%	8 18.2%
Asian	2 9.1%	2 9.1%	4 9.1%
Mixed Race	0 0%	2 9.1%	2 4.5%
White Hispanic	3 13.6%	1 4.5%	4 9.1%
Region of Enrollment (Count of Participants)
United States	22 100%	22 100%	44 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sugar Pill	Baclofen
Arm/Group Description	Placebo-treated subjects will follow the identical schedule as Baclofen subjects. placebo	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. Baclofen
Measure Participants	22	22
Scan Day 1	14.19 (1.01)	14.23 (1.20)
Scan Day 2	7.67 (1.05)	7.76 (1.10)

Adverse Events

Time Frame	Collected over a 5 year period
Arm/Group Title	Sugar Pill		Baclofen
Arm/Group Description	Placebo-treated subjects will follow the identical schedule as Baclofen subjects. placebo		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. Baclofen
All Cause Mortality
	Sugar Pill		Baclofen
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/22 (0%)		0/22 (0%)
Serious Adverse Events
	Sugar Pill		Baclofen
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/22 (0%)		0/22 (0%)
Other (Not Including Serious) Adverse Events
	Sugar Pill		Baclofen
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/22 (77.3%)		16/22 (72.7%)
Gastrointestinal disorders
Nausea	1/22 (4.5%)		4/22 (18.2%)
Digestive	4/22 (18.2%)		4/22 (18.2%)
Musculoskeletal and connective tissue disorders
musculoskeletal	0/22 (0%)		2/22 (9.1%)
Nervous system disorders
Drowsiness	6/22 (27.3%)		9/22 (40.9%)
Headache	4/22 (18.2%)		2/22 (9.1%)
Dizzy/Lightheadedness	1/22 (4.5%)		5/22 (22.7%)
Insomnia	1/22 (4.5%)		2/22 (9.1%)
Cognitive Changes	2/22 (9.1%)		4/22 (18.2%)
Psychiatric disorders
Affective Changes	0/22 (0%)		4/22 (18.2%)
Vascular disorders
Elevated Blood Pressure	1/22 (4.5%)		3/22 (13.6%)

Limitations/Caveats

The goals of the study were to identify mechanisms of baclofen's effects on smoking cue reactivity. Using other mechanisms we provided a treatment arm. Sample size was small.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.