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

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.

Study Overview

• Status: Recruiting
• Conditions: Tobacco Use Disorder
• Intervention / Treatment: Drug: Clavulanic Acid; Drug: Placebo oral capsule

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Madhura Athreya, MS; Phone Number: 573-882-2977; Email: athreyam@health.missouri.edu
• Study Contact Backup: Name: Brett E Froeliger, PhD; Phone Number: 573-882-4785; Email: froeligerb@health.missouri.edu

Study Locations

• United States
  • Missouri
    • Columbia, Missouri, United States, 65211
      • Recruiting
      • University of Missouri - Columbia
      • Contact: Madhura Athreya, MS; Phone Number: 573-882-2977; Email: athreyam@health.missouri.edu
      • Contact: Brett Froeliger, PhD; Phone Number: 513-882-4785; Email: froeligerb@health.missouri.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Entry criteria:

Inclusion Criteria all subjects:

1. Age 18-65 years
2. English fluency
3. Functional vision (with corrective lenses as needed) to complete assigned assessments and tasks
4. 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)
5. If female, provide a negative urine pregnancy test.
6. 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:

1. Sensitivity or allergy to clavulanic acid/antibiotics
2. Past head injury or primary neurological disorder associated with MRI abnormalities, including dementia, MCI, brain tumors, epilepsy, Parkinson's disease, or demyelinating diseases
3. Any physical or intellectual disability affecting completion of assessments
4. Any contraindication to MRI
5. Use of antidepressants medications with smoking cessation efficacy
6. Presence of an untreated illness or serious medical condition
7. Current or past psychosis
8. Electroconvulsive therapy in last 6 months
9. Positive pregnancy test (Urine pregnancy testing at screening and prior to fMRI scan) or currently breast feeding or BAC greater than 0.0
10. Use of carbamazepine or nitroglycerin (or any other medication deemed to be hazardous if taken with CLAV) within 14 days of study participation
11. 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
12. 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
13. 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Missouri-Columbia
• Investigators: Principal Investigator: Brett Froeliger, PhD, University of Missouri-Columbia

Study record dates

Study Major Dates

• Study Start (Actual): March 26, 2019
• Primary Completion (Estimated): August 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: October 17, 2018
• First Submitted That Met QC Criteria: October 17, 2018
• First Posted (Actual): October 19, 2018

Study Record Updates

• Last Update Posted (Actual): November 30, 2023
• Last Update Submitted That Met QC Criteria: November 28, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Tobacco Use Disorder; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Clavulanic Acid; Clavulanic Acids
• Other Study ID Numbers: 2022247

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No