Clinical trial NCT03986762: Open Label Pharmaco- Magnetic Resonance Spectrography (MRS) Study of Clavulanic Acid
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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cocaine Dependence, in Remission
Cocaine Abuse, in Remission
Cocaine-Related Disorders
Lead sponsor: Temple University
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2019-06-14
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.)

Primary outcomes:
measure: Glutamate change from baseline
timeFrame: 10-17 Days
measure: Glutamate/creatine ratio change from baseline
timeFrame: 10-17 Days
Secondary outcomes:
measure: Glutamate change after dose stoppage
timeFrame: Day 10-11
measure: Glutamate/creatine ratio change after dose stoppage
timeFrame: Day 10-11
measure: Change in brain glutamine from baseline
timeFrame: 10-17 Days
measure: Change in brain glutamine/creatine ratio from baseline
timeFrame: 10-17 Days
measure: 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.
timeFrame: 1-31 days (during and after study dosing period)
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Episcopal Hospital Medical Arts Building
state: Pennsylvania
Study officials:
affiliation: Temple University
name: Mary F Morrison, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.