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Open Label Pharmaco- Magnetic Resonance Spectrography (MRS) Study of Clavulanic Acid (CLAVMRPilot)

Primary Purpose

Cocaine Dependence, in Remission, Cocaine Abuse, in Remission, Cocaine-Related Disorders

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Clavulanic Acid

About this trial

This is an interventional treatment trial for Cocaine Dependence, in Remission

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Meet DSM-5 criteria for cocaine use disorder, moderate to severe in early remission.
Be male or female adult volunteers ages 18-65 inclusive.
If female and of childbearing potential, must have a negative pregnancy test within 48 hours of beginning the study and be willing to use acceptable contraception or be abstinent for 14 days prior to study, through the entire study and 30 days after study participation.

Exclusion Criteria:

Be unable to complete an MRI scan

(For full inclusion/exclusion criteria or for more information, please contact the site directly.)

Sites / Locations

Episcopal Hospital Medical Arts Building

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Open Label Clav

Arm Description

Outcomes

Primary Outcome Measures

Glutamate change from baseline

Change in brain glutamate concentration at Day 10-17 compared with baseline.

Glutamate/creatine ratio change from baseline

Change in brain glutamate/creatine ratio at Day 10-17

Secondary Outcome Measures

Glutamate change after dose stoppage

Change in brain glutamate concentration in 2 brain areas associated with addiction at Day 11 compared with Day 10.

Glutamate/creatine ratio change after dose stoppage

Change in brain glutamate/creatine ratio in 2 brain areas associated with addiction at Day 11 compared with Day 10.

Change in brain glutamine from baseline

Change in brain glutamine concentration in 2 brain areas at Day 10-17 compared with baseline.

Change in brain glutamine/creatine ratio from baseline

Change in glutamine/creatine ratio in 2 brain areas at Day 10-17 compared with baseline.

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.

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) parameters and 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.

Full Information

NCT ID

NCT03986762

First Posted

February 15, 2019

Last Updated

October 22, 2020

Sponsor

Temple University

Collaborators

National Institute on Drug Abuse (NIDA)

1. Study Identification

Unique Protocol Identification Number

NCT03986762

Brief Title

Open Label Pharmaco- Magnetic Resonance Spectrography (MRS) Study of Clavulanic Acid

Acronym

CLAVMRPilot

Official Title

A Phase IA Open Label Pharmaco- Magnetic Resonance Spectrography (MRS) Study of Clavulanic Acid Daily Repeated Administration in Remitted Cocaine Use Disorder Subjects

Study Type

Interventional

2. Study Status

Record Verification Date

October 2020

Overall Recruitment Status

Completed

Study Start Date

March 12, 2019 (Actual)

Primary Completion Date

December 20, 2019 (Actual)

Study Completion Date

December 20, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Temple University

Collaborators

National Institute on Drug Abuse (NIDA)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The main purpose of this study is to determine how the study drug, clavulanic acid, affects glutamate in the brain using Magnetic Resonance (MR/MRI) scans. In this study, subjects will receive the study drug, clavulanic acid and undergo 4 MRI scans. This is being studied to determine the correct dosing of clavulanic acid, and to gather data so future studies can be done to find out if this drug is helpful in treating cocaine dependence. Currently, there is no available medication treatment for cocaine dependence.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cocaine Dependence, in Remission, Cocaine Abuse, in Remission, Cocaine-Related Disorders

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

9 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Open Label Clav

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

Clavulanic Acid

Intervention Description

~10 days of Clavulanic Acid

Primary Outcome Measure Information:

Title

Glutamate change from baseline

Description

Change in brain glutamate concentration at Day 10-17 compared with baseline.

Time Frame

10-17 Days

Title

Glutamate/creatine ratio change from baseline

Description

Change in brain glutamate/creatine ratio at Day 10-17

Time Frame

10-17 Days

Secondary Outcome Measure Information:

Title

Glutamate change after dose stoppage

Description

Change in brain glutamate concentration in 2 brain areas associated with addiction at Day 11 compared with Day 10.

Time Frame

Day 10-11

Title

Glutamate/creatine ratio change after dose stoppage

Description

Change in brain glutamate/creatine ratio in 2 brain areas associated with addiction at Day 11 compared with Day 10.

Time Frame

Day 10-11

Title

Change in brain glutamine from baseline

Description

Change in brain glutamine concentration in 2 brain areas at Day 10-17 compared with baseline.

Time Frame

10-17 Days

Title

Change in brain glutamine/creatine ratio from baseline

Description

Change in glutamine/creatine ratio in 2 brain areas at Day 10-17 compared with baseline.

Time Frame

10-17 Days

Title

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.

Description

Time Frame

1-31 days (during and after study dosing period)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Meet DSM-5 criteria for cocaine use disorder, moderate to severe in early remission. Be male or female adult volunteers ages 18-65 inclusive. If female and of childbearing potential, must have a negative pregnancy test within 48 hours of beginning the study and be willing to use acceptable contraception or be abstinent for 14 days prior to study, through the entire study and 30 days after study participation. Exclusion Criteria: Be unable to complete an MRI scan (For full inclusion/exclusion criteria or for more information, please contact the site directly.)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Mary F Morrison, M.D.

Organizational Affiliation

Temple University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Episcopal Hospital Medical Arts Building

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19125

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

19128205

Citation

Uys JD, LaLumiere RT. Glutamate: the new frontier in pharmacotherapy for cocaine addiction. CNS Neurol Disord Drug Targets. 2008 Nov;7(5):482-91. doi: 10.2174/187152708786927868.

Results Reference

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PubMed Identifier

20383795

Citation

Rasmussen BA, Baron DA, Kim JK, Unterwald EM, Rawls SM. beta-Lactam antibiotic produces a sustained reduction in extracellular glutamate in the nucleus accumbens of rats. Amino Acids. 2011 Feb;40(2):761-4. doi: 10.1007/s00726-010-0589-0. Epub 2010 Apr 13.

Results Reference

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PubMed Identifier

21543969

Citation

Ward SJ, Rasmussen BA, Corley G, Henry C, Kim JK, Walker EA, Rawls SM. Beta-lactam antibiotic decreases acquisition of and motivation to respond for cocaine, but not sweet food, in C57Bl/6 mice. Behav Pharmacol. 2011 Aug;22(4):370-3. doi: 10.1097/FBP.0b013e3283473c10.

Results Reference

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PubMed Identifier

23031254

Citation

Kovalevich J, Corley G, Yen W, Rawls SM, Langford D. Cocaine-induced loss of white matter proteins in the adult mouse nucleus accumbens is attenuated by administration of a beta-lactam antibiotic during cocaine withdrawal. Am J Pathol. 2012 Dec;181(6):1921-7. doi: 10.1016/j.ajpath.2012.08.013. Epub 2012 Sep 29.

Results Reference

background

PubMed Identifier

24123328

Citation

Ramadan S, Lin A, Stanwell P. Glutamate and glutamine: a review of in vivo MRS in the human brain. NMR Biomed. 2013 Dec;26(12):1630-46. doi: 10.1002/nbm.3045. Epub 2013 Oct 4.

Results Reference

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Open Label Pharmaco- Magnetic Resonance Spectrography (MRS) Study of Clavulanic Acid

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