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

Cocaine-Related Disorders Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03986762
• Other study ID #: 25506
• Status: Completed
• Phase: Phase 1
• Start date: March 12, 2019
• Est. completion date: December 20, 2019

Study information

• Verified date: October 2020
• Source: Temple University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9
• Est. completion date: December 20, 2019
• Est. primary completion date: December 20, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.)

Related Conditions & MeSH terms

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

Intervention

Drug:
• Clavulanic Acid
~10 days of Clavulanic Acid

Locations

Country	Name	City	State
United States	Episcopal Hospital Medical Arts Building	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Temple University	National Institute on Drug Abuse (NIDA)

Country where clinical trial is conducted

United States, 

References & Publications (5)

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 ß-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. — View 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. Review. — View Citation

Rasmussen BA, Baron DA, Kim JK, Unterwald EM, Rawls SM. ß-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. — View 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. Review. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Glutamate change from baseline	Change in brain glutamate concentration at Day 10-17 compared with baseline.	10-17 Days
Primary	Glutamate/creatine ratio change from baseline	Change in brain glutamate/creatine ratio at Day 10-17	10-17 Days
Secondary	Glutamate change after dose stoppage	Change in brain glutamate concentration in 2 brain areas associated with addiction at Day 11 compared with Day 10.	Day 10-11
Secondary	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.	Day 10-11
Secondary	Change in brain glutamine from baseline	Change in brain glutamine concentration in 2 brain areas at Day 10-17 compared with baseline.	10-17 Days
Secondary	Change in brain glutamine/creatine ratio from baseline	Change in glutamine/creatine ratio in 2 brain areas at Day 10-17 compared with baseline.	10-17 Days
Secondary	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.	1-31 days (during and after study dosing period)