Glutamate-Glutamine Cycling (VCYC) During Cocaine Abstinence Using 13C-MRS

What is the purpose of this trial?

Specific Aim 1:
To measure resting-state neuroenergetics and neurotransmission, as assessed by [13C]-MRS measures of mitochondrial glucose oxidation (VTCA) and glutamate-glutamine cycling (VCYC), in the prefrontal cortex (PFC) of abstinent cocaine users and healthy controls. We will study 30 abstinent (≥ 2 weeks) cocaine-users (CU) who meet criteria for either abuse or dependence and 30 healthy control (HC) subjects at rest using [13C]-MRS.

Hypothesis:
Given prior evidence of reduced resting-state glucose uptake in PFC as measured by [18F]-FDG PET (Volkow 1992, 1993) and direct neurometabolic coupling of cortical glucose oxidation and glutamate transmission, we hypothesize that [13C]-MRS measures of VTCA and VCYC will be reduced in individuals abstinent from cocaine as compared to HCs. We will also explicitly explore potential relationships between VCYC and neurocognitive tests of PFC function and clinical outcomes (i.e., measures of relapse at 90-days outpatient follow-up).

Specific Aim 2 (Exploratory):
To explore whether open-label administration of either of three different pharmacological treatments (N-acetyl cysteine, riluzole, or pentoxifylline) increases VCYC, in cocaine users (CU) in comparison to their abstinence baseline. This exploratory aim consists of an optional medication administration component, which will follow subjects participation in Aim 1. Specifically, upon completion of baseline [13C]-MRS measures of VCYC at 2 weeks of abstinence, individuals will be assigned to either two weeks of open-label treatment with one of the following:

  1. N-acetyl cysteine (NAC) 1200 mg twice per day,
  2. Riluzole (RIL) 50 mg twice per day, or 3) Pentoxifylline (PTX) 400 mg three times per day, or 2 weeks of continued inpatient drug abstinence (no medication), followed by a second [13C]-MRS scan (i.e., at 4 weeks abstinence).

Participation Guidelines

Ages: 21 - 55 years

Gender: Both


National Institute on Drug Abuse

Start Date: 04/11/2014

End Date: 12/31/2023

Last Updated: 02/22/2018

Study HIC#: 1311013082

Get Involved

For more information about this study, contact:
Jessica Costeines
+1 203-520-6398
jessica.costeines@yale.edu

If you would prefer to contact a member of the Help us Discover team about this trial and other similar trials, please email helpusdiscover@yale.edu or call 1-877-978-8348.

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