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

Sponsor
Temple University (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT04411914
Collaborator
Beth Israel Deaconess Medical Center (Other), University of Pennsylvania Perelman School of Medicine (Other)
13
Enrollment
1
Location
2
Arms
18.9
Anticipated Duration (Months)
0.7
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease Intervention/Treatment Phase
  • Drug: Clavulanic Acid Only Product
  • Other: Placebo
 Phase 1

Detailed Description

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. Structural MRI, functional MRI and MRS scans will be done throughout the study. At the time of each scan, safety of the subject to complete the scan will be re-assessed. Subjective, cognitive, and adverse effect assessments, blood pressure and pulse will be performed daily.

Study Design

Study Type:
Interventional
Actual Enrollment :
13 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Randomized, double-blind, placebo-controlled, parallel group inpatient studyRandomized, double-blind, placebo-controlled, parallel group inpatient study
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase IB Double Blind, Placebo Controlled, Pharmaco- Magnetic Resonance Spectroscopy (MRS) Inpatient Study of Clavulanic Acid 500, 750, 1000 mg Daily Repeated Administration in Early Remitted Cocaine Use Disorder Subjects
Actual Study Start Date :
Sep 1, 2020
Actual Primary Completion Date :
Nov 23, 2021
Anticipated Study Completion Date :
Mar 31, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: Clavulanic Acid

9 Participants will receive 500 mg of CLAV at baseline. Subjects who can tolerate 500 mg/day for 3 days (or matched placebo) will have a dose escalation to 750 mg/day for 3 days. Subjects who can tolerate 750mg/day for three days will have a dose escalation to 1000mg for 4 days.

Drug: Clavulanic Acid Only Product
Drug will be given in 250mg capsules.
Placebo Comparator: Placebo

3 participants will 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.

Other: Placebo
Placebo

Outcome Measures

Primary Outcome Measures

  1. Brain glutamate concentration in the anterior cingulate (ACC) [Brain glutamate will be analyzed prior to dosing, 3 days after baseline, 6 days after baseline, 10 days after baseline, and 24 hours after the last dose (11 days after baseline).]

    Brain glutamate concentration will be analyzed before, after and during drug administration (CLAV 500, 750, 1000 mg/day) up to an 11 day period in subjects with cocaine use disorder compared with baseline.

Secondary Outcome Measures

  1. Changes in craving associated neurocircuitry from baseline [Craving associated neurocircuitry will be analyzed prior to dosing, 3 days after baseline, 6 days after baseline, 10 days after baseline, and 24 hours after the last dose (11 days after baseline).]

    Craving-associated neurocircuitry (frontal-striatal-thalamic connectivity) will be examined with functional Magnetic Resonance Imaging (fMRI).

  2. Craving [Craving will be analyzed daily from baseline until discharge, up to an 11 day period.]

    Craving will be evaluated by fMRI neurocircuitry and subjective assessments

  3. Change in brain glutamine from baseline [Brain glutamine will be analyzed prior to dosing, 3 days after baseline, 6 days after baseline, 10 days after baseline, and 24 hours after the last dose (11 days after baseline).]

    Brain glutamine concentration will be analyzed before, after and during drug administration (CLAV 500, 750, 1000 mg/day) up to an 11 day period in subjects with cocaine use disorder compared with baseline.

  4. Number of Participants With Treatment-related Adverse Events (AEs) as Assessed by Comprehensive Metabolic Panel, Complete Blood Count, Ekg, Urinalysis, C-SSRS, and Any Self-reported Change in Health. [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, indications of suicidal ideation or behavior on the Columbia Suicide Severity Rating Scale (C-SSRS), 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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 70 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  1. Be able to verbalize understanding of consent form

  2. Be male or female adult volunteers ages 18-65 inclusive.

  3. Have a DSM-5 diagnosis of cocaine use disorder, moderate to severe in early remission

  4. 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.)

  5. 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:

  1. Have a current DSM-V 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 UDS. Alcohol use disorder and marijuana use disorder, mild without withdrawal symptoms, will be permitted.

  2. Have any previous medically adverse reaction to CLAV, Augmentin, penicillin, Ticarcillin, cephalosporin, or any beta-lactam drug.

  3. 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.

  4. Report having human immunodeficiency virus (HIV) infection or test positive for HIV during screening

  5. Be pregnant (females).

  6. Unable to tolerate MRI scan for duration of 60 minutes for physical or psychological reasons.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Temple University Episcopal Hospital Philadelphia Pennsylvania United States 19125

Sponsors and Collaborators

  • Temple University
  • Beth Israel Deaconess Medical Center
  • University of Pennsylvania Perelman School of Medicine

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
Temple University
ClinicalTrials.gov Identifier:
NCT04411914
Other Study ID Numbers:
  • 26876
First Posted:
Jun 2, 2020
Last Update Posted:
Mar 2, 2022
Last Verified:
Feb 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Cocaine-Related Disorders
Clavulanic Acids
Clavulanic Acid

Study Results

No Results Posted as of Mar 2, 2022