Glutamate-Glutamine Cycling (VCYC) During Cocaine Abstinence Using 1H-MRS

Phase 1

Completed

• Conditions: Healthy; Cocaine Dependence
• Interventions: Drug: N-acetyl cysteine; Diagnostic Test: 1H MRS; Diagnostic Test: [11C]APP311 PET scan; Diagnostic Test: [18F]FDG PET scan

• Registration Number: NCT02124941
• Lead Sponsor: Yale University

Brief Summary

This study is designed to look at the relationship between brain glucose utilization, neurotransmission (e.g., glutamate, also known as the main excitatory amino-acid neurotransmitter in the brain), and synaptic density. This relationship will be explored in the brain's prefrontal cortex, an area important in decision-making and impulsivity.

Detailed Description

Not available

Study Timeline

• Study Start: 2014-02
• Study First Submitted: 2014-04-22
• Study First Submitted QC: 2014-04-24
• Study First Posted: 2014-04-28
• Primary Completion: 2022-08-14
• Study Completion: 2022-08-14
• Status Verified: 2023-07
• Last Update Submitted: 2023-07-05
• Last Update Posted: 2023-07-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 6

Inclusion Criteria

1. Age 18-55 years;
2. Voluntary, written, informed consent;
3. Physically healthy by medical history, physical, neurological, ECG and laboratory examinations;
4. DSM-IV criteria for Cocaine Dependence (304.20) (Note: subjects will also meet DSM-5 criteria for Cocaine Use Disorder);
5. Documented evidence (by urine toxicology) of abstinence from cocaine (2 weeks for scan 1, and 2 and 4 weeks for scans 2 and 3, respectively)
6. Full scale and verbal IQs > 80;
7. For females, a negative serum pregnancy test (β-HCG) at screening and negative urine pregnancy test on PET scan day prior to imaging.

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Exclusion Criteria

1. A history of other substance dependence (e.g., alcohol, opiates, sedative hypnotics), except for nicotine;
2. A primary DSM-IV Axis I major psychiatric disorder (e.g., schizophrenia, bipolar disorder, major depression, etc.) as determined by the Structured Clinical Interview for DSM-IV (SCID);
3. A history of significant medical (e.g., cardiovascular, diabetic/metabolic) or neurological (e.g., cerebrovascular, seizure, traumatic brain injury) illness;
4. Current use of psychotropic and/or potentially psychoactive prescription medications;
5. Medical contraindications to participation in a magnetic resonance imaging procedure (e.g., ferromagnetic implants/foreign bodies, claustrophobia, cardiac pacemaker, prosthetic valve, otologic implant, etc.);
6. For females, laboratory (β-HCG) evidence of pregnancy, physical evidence of pregnancy;
7. For subjects interested in pharmacotherapy component, history of allergies to NAC and current elevation on liver function tests above twice the normal limit;
8. Subjects with history of prior radiation exposure for research purposes within the past year such that participation in this study would place them over FDA limits for annual radiation exposure. This guideline is an effective dose of 5 rem received per year;
9. Subjects with current, past or anticipated exposure to radiation in the work place within one year of proposed research PET scans;
10. History of a bleeding disorder or are currently taking anticoagulants (such as Coumadin, Heparin, Pradaxa, Xarelto);
11. Blood donation within eight weeks of the start of the study.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Medication (NAC & placebo) administration	N-acetyl cysteine	Upon completion of baseline (abstinence) 1H-MRS scanning at 7T, CU and HC subjects will participate in two additional 1H-MRS scans, including after 2 weeks of placebo and 2 weeks of NAC administration (3600 mg/day) given in double-blind, randomized, counterbalanced order.
1H MRS	1H MRS	All subjects will undergo three magnetic resonance spectroscopy (1H-MRS) scans, including before and after two-weeks of placebo and NAC administration.
[11C]APP311 PET scan	[11C]APP311 PET scan	All subjects will undergo \[11C\]APP311 PET imaging to investigate whether there are differences in synaptic integrity / neuronal plasticity in the brains of individuals abstinent from cocaine compared to healthy controls at baseline.
[18F]-FDG PET scan	[18F]FDG PET scan	All subjects will undergo \[18F\]FDG PET to establish previously demonstrated reductions in glucose utilization in PFC and assess VS/nucleus accumbent metabolism at baseline.

Primary Outcome Measures

Name	Time	Method
GLU and GLU/GLN ratios	4 weeks

Trial Locations

Locations (1)

Connecticut Mental Health Center; 🇺🇸 New Haven, Connecticut, United States