An fMRI Study of the Effects of Clavulanic Acid on Drug Addiction

Study Overview
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Brief Summary
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This research study is looking into the effects of clavulanic on smoking behavior in adult cigarette smokers. The primary study hypothesis is that, compared to placebo, clavulanic acid will reduce smoking over the course of the study.

Official Title
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An fMRI Study of the Effects of Clavulanic Acid on Drug Addiction

Conditions
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Tobacco Use Disorder

Intervention / Treatment
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* Drug: Clavulanic Acid
* Drug: Placebo oral capsule


Participation Criteria
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Eligibility Criteria
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Entry criteria: Inclusion Criteria all subjects: Age 18-65 years English fluency Functional vision (with corrective lenses as needed) to complete assigned assessments and tasks Smoke > 10 cigarettes/day for a minimum of 2 yrs. and have an expired carbon monoxide (CO) concentration of ≥ 10 ppm (to confirm inhalation at screening and scanning) If female, provide a negative urine pregnancy test. Agrees to refrain from all other tobacco (i.e., dip/chew, cigars, cigarillos) and/or nicotine products (i.e., e-cigs, patches, gum/lozenges, inhalers/sprays) for the duration of study participation Exclusion Criteria all subjects: Sensitivity or allergy to clavulanic acid/antibiotics Past head injury or primary neurological disorder associated with MRI abnormalities, including dementia, MCI, brain tumors, epilepsy, Parkinson's disease, or demyelinating diseases Any physical or intellectual disability affecting completion of assessments Any contraindication to MRI Use of antidepressants medications with smoking cessation efficacy Presence of an untreated illness or serious medical condition Current or past psychosis Electroconvulsive therapy in last 6 months Positive pregnancy test (Urine pregnancy testing at screening and prior to fMRI scan) or currently breast feeding or BAC greater than 0.0 Use of carbamazepine or nitroglycerin (or any other medication deemed to be hazardous if taken with CLAV) within 14 days of study participation Abnormal liver function determined by Complete Metabolic Panel - liver enzymes outside normal ranges of AST (SGOT) 5-40 unites/L and ALT( SGPT) 7-56units/L Abnormal renal function determined by Complete Metabolic Panel - outside normal ranges of BUN 6-24 mg /dl and Creatinine level 0.6 -1.2 mg /dl male, 0.5-1.1mg /dl female Any other condition or concern that in the investigator's opinion would impact participant safety, compliance with study instructions, or potentially confound the interpretation of the study results

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Clav<br>4-day 125 bid oral capsule administration | Drug: Clavulanic Acid<br>* Beta lactamase inhibitor for smoking cessation<br>|
| Placebo Comparator: Placebo<br>4-day, twice-daily oral capsule administration | Drug: Placebo oral capsule<br>* placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cigarette Smoking | Biochemical smoking assessment (breath carbon monoxide) at each study visit. | 5 days | 
| Self Reported Side Effects | Number of reported side effects | 5 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Magnitude of change in BOLD fMRI brain response to smoking related images | Measure the effects of Clavulanic Acid on fMRI BOLD response to images (change from baseline to end of study) while participants undergo functional magnetic resonance imaging | 4 days | 
| Magnitude of change in resting-stated fMRI brain connectivity | Measure the effects of Clavulanic Acid on resting-state functional connectivity (change from baseline to end of study) while participants undergo functional magnetic resonance imaging. | 4 days |