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

Healthy Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02124941
• Other study ID #: 1311013082
• Secondary ID: 1R21DA044005-011
• Status: Completed
• Phase: Phase 1
• Start date: February 2014
• Est. completion date: August 14, 2022

Study information

• Verified date: July 2023
• Source: Yale University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: August 14, 2022
• Est. primary completion date: August 14, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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 (ß-HCG) at screening and negative urine pregnancy test on PET scan day prior to imaging.

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 (ß-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.

Related Conditions & MeSH terms

• Cocaine Dependence
• Cocaine-Related Disorders
• Healthy

Intervention

Drug:
• N-acetyl cysteine
Upon completion of baseline (abstinence) 1H-MRS scanning, 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.

Diagnostic Test:
• [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.
• 1H MRS
All subjects will undergo three magnetic resonance spectroscopy (1H-MRS) scans at 7T, including before and after two-weeks of placebo and NAC administration.
• [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.

Locations

Country	Name	City	State
United States	Connecticut Mental Health Center	New Haven	Connecticut

Sponsors (2)

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

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	GLU and GLU/GLN ratios		4 weeks