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

NCT ID: NCT02124941

Last Updated: 2023-07-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-02-28
• Study Completion Date: 2022-08-14

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.

Conditions

Cocaine Dependence; Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

1H MRS

All subjects will undergo three magnetic resonance spectroscopy (1H-MRS) scans, including before and after two-weeks of placebo and NAC administration.

Group Type: EXPERIMENTAL

1H MRS

Intervention Type: DIAGNOSTIC_TEST

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

[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.

Group Type: EXPERIMENTAL

[18F]FDG PET scan

Intervention Type: DIAGNOSTIC_TEST

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.

[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.

Group Type: EXPERIMENTAL

[11C]APP311 PET scan

Intervention Type: DIAGNOSTIC_TEST

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.

Medication (NAC & placebo) administration

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.

Group Type: ACTIVE_COMPARATOR

N-acetyl cysteine

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

[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.

Intervention Type: DIAGNOSTIC_TEST

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.

Intervention Type: DIAGNOSTIC_TEST

[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.

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role: collaborator

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gustavo Angarita, MD

Role: PRINCIPAL_INVESTIGATOR

Yale University

Locations

Connecticut Mental Health Center

New Haven, Connecticut, United States

Countries

United States

Other Identifiers

1R21DA044005-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1R21DA043055-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1311013082

Identifier Type: -

Identifier Source: org_study_id