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NCT04411914

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

Completed Phase 1 Results posted Last updated 22 June 2023
What this trial tests

Phase 1 trial testing Clavulanic Acid in Cocaine Dependence in 13 participants. Completed in 31 March 2022.

Timeline
1 September 2020
Primary endpoint
23 November 2021
31 March 2022

Quick facts

Lead sponsorTemple University
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment13
Start date1 September 2020
Primary completion23 November 2021
Estimated completion31 March 2022
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

Temple University

Who can join

Adults 18 to 70, any sex, with Cocaine Dependence. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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

GroupValue95% CI
Clavulanic Acid Day 10-0.9000
Clavulanic Acid Baseline0.3333
Changes in Resting State Network Connectivity From Baseline Secondary · 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

GroupValue95% CI
Rs-fMRI and CCQ on Day 10 CLAV-0.8333
Craving Secondary · 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.

GroupValue95% CI
Male CLAV Subjects--CCQ on Day 107± 16
Male PBO Subjects--CCQ Score Day 10-22± 10
Female CLAV Subjects--CCQ Score Day 10-15± 21
Femaile PBO Subjects--CCQ Scores Day 1049± 0
Change in Brain Glutamine From Baseline Secondary · 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.

GroupValue95% CI
Clavulanic Acid (CLAV) Group Baseline1.5± 1.0
Clavulanic Acid Day 102.1± 2.0
Placebo Group Baseline0.8± 0.3
Placebo Group Day 100.7± 0.6
Number of Participants With Treatment-related Adverse Events (AEs) Secondary · 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

GroupValue95% CI
Clavulanic Acid6
Placebo1

Adverse events — posted to ClinicalTrials.gov

Time frame: 24 days. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Clavulanic Acid Treatment Period 1-500mg/Day
Serious: 0/10 (0%)
Deaths: 0/10
CLavulanic Acid Treatment Period 2-750mg.Day
Serious: 0/9 (0%)
Deaths: 0/9
Clavulanic Acid Treatment Period 3--1000mg/Day
Serious: 0/9 (0%)
Deaths: 0/9
Placebo
Serious: 0/3 (0%)
Deaths: 0/3
Other adverse events (13 terms — click to expand)

ReactionSystemClavulanic Acid Treatment …CLavulanic Acid Treatment …Clavulanic Acid Treatment …Placebo
NauseaGastrointestinal disorders
flatulenceGastrointestinal disorders
loose stoolGastrointestinal disorders
stomach painGastrointestinal disorders
HeartburnGastrointestinal disorders
Elevated Liver Function TestsHepatobiliary disorders
High blood pressureVascular disorders
ItchingSkin and subcutaneous tissue disorders
Swollen feetSkin and subcutaneous tissue disorders
HeadacheNervous system disorders
LightheadedNervous system disorders
Joint painMusculoskeletal and connective tissue disorders
PriapismReproductive system and breast disorders

Data from ClinicalTrials.gov NCT04411914 adverse events section.

Sponsor's own description

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

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Clavulanic Acid Decreases Cocaine Cue Reactivity in Addiction-Related Brain Areas, a Randomized fMRI Pilot Study.
    Callans LS, Philogene-Khalid H, Jagannathan K, Cunningham R, et al · · 2024 · cited 2× · PMID 38601830 · DOI 10.64719/pb.4485
  2. Neuroimmune modulators as novel pharmacotherapies for substance use disorders.
    Grodin EN. · · 2024 · cited 1× · PMID 38435721 · DOI 10.1016/j.bbih.2024.100744
  3. Clavulanic Acid-Mediated Increases in Anterior Cingulate Glutamate Levels are Associated With Decreased Cocaine Craving and Brain Network Functional Connectivity Changes.
    Maser J, Morrison MF, Khalid HP, Cunningham R, et al · · 2024 · PMID 39045086 · DOI 10.1016/j.curtheres.2024.100751

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Other trials of Clavulanic Acid

Trials testing the same drug.

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