Pharmaco-Magnetic Resonance Spectroscopy (MRS) Study of Clavulanic Acid

NCT04411914 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: 26876U01DA048517
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

A dose-escalation study to determine the optimum dose of Clavulanic Acid (CLAV) for effects on craving and efficacy.

Conditions

Cocaine Dependence

Outcome Measures

Primary Outcomes (1)

• Brain Glutamate Concentration in the Anterior Cingulate Cortex (ACC) in Subjects With Cocaine Use Disorder (CUD) Treated With Escalating Doses of Clavulanate (CLAV)

  Brain glutamate concentration in the ACC (based on Magnetic Resonance Spectroscopy (MRS)) will be correlated with cocaine craving (measured by Cocaine Craving Questionnaire (CCQ)) in subjects receiving escalating doses of CLAV for 10 days. Measurement will be made at baseline and Day 10 of CLAV (1000 mg/day) in subjects with cocaine use disorder.

  ACC glutamate and CCQ will be measured and correlated on Day 10 of treatment with CLAV compared with baseline.

Secondary Outcomes (4)

• Changes in Resting State Network Connectivity From Baseline

  Assessment was done at the end of Period 1, 2 and 3 detailed above. Data from the end of Period 3 (Day 10, 1000mg CLAV) are reported.

• Craving

  CCQ-45 questionnaires were completed daily during the study. Data from day 10 adjusted for baseline score are reported.

• Change in Brain Glutamine From Baseline

  Brain glutamine will be analyzed at baseline (Day 1 prior to CLAV or PBO dose) and at Day 10 day (having completed Periods 1, 2 and 3 (CLAV 500mg/day for 3 days, 750 mg/day for 3 days and 1000 mg/day for 4 days).

• Number of Participants With Treatment-related Adverse Events (AEs)

  1-24 days (during and up to 2 weeks after study dosing period)

Study Arms (2)

Clavulanic Acid

EXPERIMENTAL

Participants will receive 10 days of CLAV-- Period 1: 500 mg/day for days 1-3; Period 2: 750 mg/day for days 4-6; Period 3: 1000 mg/day for days 7-10.

Drug: Clavulanic Acid

Placebo

PLACEBO COMPARATOR

Participants will receive 10 days of placebo and will have a "dose" escalation at the same time as the experimental group. They will be given additional placebo pills to match the number given to the experimental group (i.e. 2 PBO capsules/day for days 1-3, 3 PBO capsules/day days 4-6 and 4 PBO capsules/day for days 7-10).

Other: Placebo

Interventions

Clavulanic Acid DRUG

Drug will be given in 250mg capsules.

Clavulanic Acid

Placebo OTHER

Placebo

Also known as: microcrystalline cellulose

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be able to verbalize understanding of consent form
• Be male or female adult volunteers ages 18-65 inclusive.
• Have a Diagnostic and Statistical Manual-5 (DSM-5) diagnosis of cocaine use disorder, moderate to severe in early remission
• Have a Body Mass Index (BMI) of 17.5 to 39.9 kg/m2; and a total body weight of at least 45 kg (99 lbs.)
• 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.

You may not qualify if:

• Have a current DSM-5 substance use disorder, mild, moderate, or severe, on any drug of abuse other than nicotine, caffeine, and cocaine use disorder in early remission verified by Urine Drug Screen (UDS). Alcohol use disorder and marijuana use disorder, mild without withdrawal symptoms, will be permitted.
• Have any previous medically adverse reaction to CLAV, Augmentin, penicillin, Ticarcillin, cephalosporin, or any beta-lactam drug.
• Have any illness, condition, and use of medications, in the opinion of the principal investigator, sub-investigators which would preclude safe and/or successful completion of the study.
• Report having human immunodeficiency virus (HIV) infection or test positive for HIV during screening
• Be pregnant (females).
• Unable to tolerate MRI scan for duration of 60 minutes for physical or psychological reasons.

Sponsors & Collaborators

• Temple University: lead
• Beth Israel Deaconess Medical Center: collaborator
• University of Pennsylvania: collaborator
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Temple University Episcopal Hospital

Philadelphia, Pennsylvania, 19125, United States

Location

Related Publications (2)

• 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.

  PMID: 26543027 BACKGROUND

• Callans LS, Philogene-Khalid H, Jagannathan K, Cunningham R, Yu D, Lu X, Walters MI, Morrison MF. Clavulanic Acid Decreases Cocaine Cue Reactivity in Addiction-Related Brain Areas, a Randomized fMRI Pilot Study. Psychopharmacol Bull. 2024 Apr 4;54(2):8-14. doi: 10.64719/pb.4485.

  PMID: 38601830 DERIVED

MeSH Terms

Conditions

Cocaine-Related Disorders

Interventions

Clavulanic Acid; microcrystalline cellulose

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Clavulanic Acids; beta-Lactams; Lactams; Amides; Organic Chemicals; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Mary Morrison, MD, MS
• Organization: Temple University

mary.morrison@temple.edu

215=707=4037

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized, double-blind, placebo-controlled, parallel group inpatient study

Study Record Dates

• First Submitted: May 20, 2020
• First Posted: June 2, 2020
• Study Start: September 1, 2020
• Primary Completion: November 23, 2021
• Study Completion: March 31, 2022
• Last Updated: June 22, 2023
• Results First Posted: June 22, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)