Clavulanic Acid for the Treatment of Cocaine Use Disorder

A Randomized, Double-Blind, Placebo-Controlled Phase 2a Pilot Study to Assess the Efficacy and Safety of Clavulanic Acid vs. Placebo for the Treatment of Cocaine Use Disorder

A dose escalation study to assess the efficacy and safety of Clavulanic Acid (CLAV) vs. placebo (PBO) for the treatment of cocaine use disorder (CUD)

Study Overview

• Status: Active, not recruiting
• Conditions: Cocaine Dependence
• Intervention / Treatment: Drug: Clavulanic Acid Only Product; Drug: Placebo

Detailed Description

This pilot study is indicated for treatment of moderate to severe cocaine use disorder. It is a randomized, placebo-controlled, parallel group, multi-center pilot study to compare the efficacy of 500-750mg/day clavulanic acid vs. placebo in addition to weekly medication management therapy. Subjective, cognitive, and adverse effect assessments, blood pressure and pulse will be performed 1-3 times weekly.

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • South Carolina
    • Charleston, South Carolina, United States, 29403
      • MUSC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Be able to verbalize understanding of consent form, able to provide written informed consent, and verbalize willingness to complete study procedures
• Be male or female adult volunteers ages 18-70 inclusive.
• Have a Diagnostic and Statistical Manual (DSM-V) diagnosis of cocaine use disorder, moderate to severe in early remission with a duration of regular (weekly or more) cocaine (either snorted, smoked or injected) for at least one year.
• Have a history and brief physical examination that demonstrate no clinically significant contraindication for participating in the study, and/ or significant or unstable medical or psychiatric illness.

Exclusion Criteria:

• Meets DSM-V criteria for dependence on any substance other than cocaine and mild to moderate alcohol or marijuana (except nicotine or caffeine), determined by the structured clinical interview for DSM-V.
• Allergy to clavulanic acid, penicillin, or any beta-lactam drug.
• Meets current or lifetime DSM-V criteria for schizophrenia or any psychotic disorder or organic mental disorder. Subject meets current DSM-V diagnosis of any other clinically significant psychiatric disorder that will interfere with study participation.
• Severe physical or medical illnesses such as AIDS or active hepatitis.
• If female, tests positive on a pregnancy test, is contemplating pregnancy in the next 6 months, is nursing, or is not using an effective contraceptive method (if relevant)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Clavulanic Acid; Participants may receive 500 mg of CLAV at baseline. Subjects who are using cocaine once per week or more and who can tolerate 500 mg/day for 4 weeks, will have a dose escalation to 750 mg/day. If tolerated, 750mg/day will be maintained for 8 weeks, otherwise the dose will decrease to 500mg/day.	Drug: Clavulanic Acid Only Product; Drug will be given in 250mg capsules; Other Names: Potassium clavulanate
Placebo Comparator: Placebo; Participants may receive placebo and serve as a control group. They will be blinded to their condition and will have a "dose" escalation at the same time as the experimental group, and be given additional placebo pills to match the number given to the experimental group.	Drug: Placebo; Capsule with no active medication - identical to drug capsule; Other Names: microcrystalline cellulose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in relapse to cocaine use in CLAV group vs PBO group	Cocaine-free weeks are measured by self-report using Timeline Follow Back (TLFB) and confirmed by urine drug screen.	Last 3 weeks of 12 week study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in weekly cocaine use will be greater in the CLAV group vs. PBO group	Cocaine-free visits are measured by self-report using TLFB confirmed by urine drug screen	TLFB and UDS will be administered 1-3 times per week and at follow-up
Changes in subject health and function, quality-of-life, will be greater in the CLAV group vs. PBO group	Medical Outcomes Study Quality of Life Scale short form 36, will determine whether CLAV treatment is associated with improved QOL	Baseline, week 4, week 8, week 12
Clavulanic acid 500-750 mg/day for 12 weeks will be safe and reasonably well tolerated	Safety and tolerability as assessed by the rates of occurrence of adverse events (AEs) and the severity	1-3 times per week and at follow-up
Cocaine craving will be decreased more by CLAV vs. PBO	Changes in craving will be greater in the CLAV group compared with PBO group, as measured by the cocaine craving questionnaire (CCQ), adjusted for baseline and sex	1-3 times per week and at follow-up
Changes in weekly abstinence in the CLAV group vs. PBO group	Abstinence from cocaine by week will be measured by self report and urine drug screen	Self reported cocaine use and Urine Drug Screen (UDS) will be administered 1-3 times per week and at follow-up

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in withdrawal symptoms over weeks 1, 2, 3 will occur in CLAV vs PBO group	Withdrawal symptoms will be measured using the Cocaine Selective Severity Assessment (CSSA)	Weekly for 3 weeks
Executive control will change more in the CLAV group compared with the PBO group after 12 weeks	Delay discounting will measure executive control	Baseline, week 4, week 8, week 12
Adverse Childhood Experiences (ACE) may correlate with cocaine relapse	Relationship between baseline scores from the ACE scale and abstinence outcomes in CLAV group will be compared to PBO group	Baseline, week 12, follow-up

Collaborators and Investigators

• Sponsor: Temple University
• Collaborators: Medical University of South Carolina; University of Pennsylvania; Research Foundation for Mental Hygiene, Inc.
• Investigators: Principal Investigator: Mary Morrison, MD, MS, Temple University

Publications and helpful links

General Publications

• Kim J, John J, Langford D, Walker E, Ward S, Rawls SM. Clavulanic acid enhances glutamate transporter subtype I (GLT-1) expression and decreases reinforcing efficacy of cocaine in mice. Amino Acids. 2016 Mar;48(3):689-696. doi: 10.1007/s00726-015-2117-8. Epub 2015 Nov 5.

Study record dates

Study Major Dates

• Study Start (Actual): May 3, 2023
• Primary Completion (Estimated): July 1, 2024
• Study Completion (Estimated): July 1, 2024

Study Registration Dates

• First Submitted: September 15, 2022
• First Submitted That Met QC Criteria: September 27, 2022
• First Posted (Actual): September 30, 2022

Study Record Updates

• Last Update Posted (Actual): May 2, 2024
• Last Update Submitted That Met QC Criteria: April 30, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Cocaine-Related Disorders; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Clavulanic Acid; Clavulanic Acids
• Other Study ID Numbers: 30076

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