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

NCT ID: NCT04411914

Last Updated: 2023-06-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-01
• Study Completion Date: 2022-03-31

Brief Summary

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

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.

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.

Conditions

Cocaine Dependence

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Clavulanic Acid

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.

Group Type: EXPERIMENTAL

Clavulanic Acid

Intervention Type: DRUG

Drug will be given in 250mg capsules.

Placebo

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).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Placebo

Interventions

Clavulanic Acid

Drug will be given in 250mg capsules.

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: OTHER

Other Intervention Names

microcrystalline cellulose

Eligibility Criteria

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 Diagnostic and Statistical Manual-5 (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-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.

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Beth Israel Deaconess Medical Center

OTHER

Sponsor Role: collaborator

University of Pennsylvania

OTHER

Sponsor Role: collaborator

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role: collaborator

Temple University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Temple University Episcopal Hospital

Philadelphia, Pennsylvania, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 26543027 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 38601830 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

U01DA048517

Identifier Type: NIH

Identifier Source: secondary_id

View Link

26876

Identifier Type: -

Identifier Source: org_study_id