Clinical trial NCT05562349: Clavulanic Acid for the Treatment of Cocaine Use Disorder
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Cocaine Dependence
Lead sponsor: Temple University
Sponsor class: OTHER
Collaborators: name: University of Pennsylvania
name: Medical University of South Carolina
name: Research Foundation for Mental Hygiene, Inc.
First posted: 2022-09-30
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, double-blind, placebo-controlled, parallel group study
Primary purpose: TREATMENT

Brief summary: 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)

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Changes in relapse to cocaine use in CLAV group vs PBO group
timeFrame: Last 3 weeks of 12 week study
Secondary outcomes:
measure: Changes in weekly abstinence in the CLAV group vs. PBO group
timeFrame: Self reported cocaine use and Urine Drug Screen (UDS) will be administered 1-3 times per week and at follow-up
measure: Changes in weekly cocaine use will be greater in the CLAV group vs. PBO group
timeFrame: TLFB and UDS will be administered 1-3 times per week and at follow-up
measure: Changes in subject health and function, quality-of-life, will be greater in the CLAV group vs. PBO group
timeFrame: Baseline, week 4, week 8, week 12
measure: Clavulanic acid 500-750 mg/day for 12 weeks will be safe and reasonably well tolerated
timeFrame: 1-3 times per week and at follow-up
measure: Cocaine craving will be decreased more by CLAV vs. PBO
timeFrame: 1-3 times per week and at follow-up
Other outcomes:
measure: Changes in withdrawal symptoms over weeks 1, 2, 3 will occur in CLAV vs PBO group
timeFrame: Weekly for 3 weeks
measure: Executive control will change more in the CLAV group compared with the PBO group after 12 weeks
timeFrame: Baseline, week 4, week 8, week 12
measure: Adverse Childhood Experiences (ACE) may correlate with cocaine relapse
timeFrame: Baseline, week 12, follow-up
Locations:
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Charleston
country: United States
facility: MUSC
state: South Carolina
Study officials:
affiliation: Temple University
name: Mary Morrison, MD, MS
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.