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Completed

NCT Number: NCT04411914

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

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

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Key information

Conditions

Cocaine Dependence Chemically-Induced Disorders Cocaine-Related Disorders Mental Disorders Substance-Related Disorders

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Temple University Episcopal Hospital

Philadelphia, Pennsylvania, 19125, United States

About this study

This is a randomized, double-blind, placebo-controlled, parallel group inpatient study of clavulanic acid for 10 days in adults (18-65) seeking treatment for cocaine use disorder. For those subjects who can tolerate 500 mg/day for 3 days (or matched placebo), there will be a forced dose escalation to 750 mg/day for 3 days. Subjects who can tolerate 750 mg/day for three days will have a forced dose escalation to 1000 mg/day for 4 days until the study ends.

Thus, there are 3 Periods for each participant:

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

Subjective, cognitive, and adverse effect assessments, blood pressure and pulse will be performed daily. Structural MRI, resting state MRI (rs-fMRI), functional MRI (fMRI) and Magnetic Resonance Spectroscopy (MRS) scans will be done at baseline and on Days 3, 6 and 10 of the study. At the time of each scan, safety of the subject to complete the scan will be re-assessed. fMRI was not done at baseline.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

Exclusion criteria

  • 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.

Treatment and study plan

Clavulanic Acid

Drug

Drug will be given in 250mg capsules.

Placebo

Other

Placebo

Other names: microcrystalline cellulose

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)

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

    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.

Secondary outcomes

  1. Changes in Resting State Network Connectivity From Baseline

    Time frame: 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-associated neurocircuitry (frontal-striatal-thalamic connectivity) will be examined with resting state functional Magnetic Resonance Imaging (rs-fMRI) and Cocaine Craving Questionnaire (CCQ-45). The CCQ is comprised of five 9-item sub-scales (desire to use cocaine, intention and planning to use cocaine, anticipation of positive outcome from use, anticipation of relief from withdrawal or dysphoria, and lack of control over use) measured on a scale of 1 to 7, total scores ranging from 45 to 315 with higher numbers indicating increased craving.. The rs-fMRI activity and CCQ were assessed in the 9 participants at baseline and at the end of each of 3 periods. rs-fMRI activity and CCQ were correlated using the Spearman Correlation Coefficient calculation. A negative correlation coefficient indicates an inverse relationship between the assessments; higher rs-fMRI activity correlates with lower craving.

  2. Craving

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

    Craving will be evaluated by Cocaine Craving Questionnaire (CCQ-45). The CCQ is comprised of five 9-item sub-scales (desire to use cocaine, intention and planning to use cocaine, anticipation of positive outcome from use, anticipation of relief from withdrawal or dysphoria, and lack of control over use) measured on a scale of 1 to 7, total scores ranging from 45 to 315 with higher numbers indicating increased craving. The results are the CCQ scores on day 10 minus the baseline scores before starting study drug.

  3. Change in Brain Glutamine From Baseline

    Time frame: 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).

    Change in brain glutamine (Gln) concentration in the ACC at Day 10 compared to baseline as assessed by MRS in the ACC.

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

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

    Adverse events (AES) will be defined as any clinically significant changes in vital signs, clinically significant change in Electrocardiogram (EKG) from baseline measurement, clinically significant changes in laboratory bloodwork (Complete blood count, comprehensive metabolic panel, urinalysis), or any self reported side effects compared with baseline. AEs will be collected throughout the study and reviewed by a physician. An evaluation of AE severity (mild, moderate, severe) will be evaluated by a physician based on participant self-report. AEs per subject will be listed by organ system, and the number of AEs within the subject population will be totaled.

Sponsors and collaborators

Lead sponsor

Temple University

Other

Collaborators

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

Registry information

Official study title

A Phase 1B Double Blind, Placebo (PBO) Controlled, Pharmaco- Magnetic Resonance Spectroscopy (MRS) Inpatient Study of Clavulanic Acid (CLAV) 500, 750, 1000 mg Daily Repeated Administration in Early Remitted Cocaine Use Disorder Subjects

Important dates

Study start
2020
Primary completion
2021
Study completion
2022
First posted
Jun 2, 2020
Registry last updated
Jun 22, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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