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

Primary Purpose

Cocaine Dependence, Healthy

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

N-acetyl cysteine

[18F]FDG PET scan

1H MRS

[11C]APP311 PET scan

About this trial

This is an interventional diagnostic trial for Cocaine Dependence

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Age 18-55 years;
Voluntary, written, informed consent;
Physically healthy by medical history, physical, neurological, ECG and laboratory examinations;
DSM-IV criteria for Cocaine Dependence (304.20) (Note: subjects will also meet DSM-5 criteria for Cocaine Use Disorder);
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)
Full scale and verbal IQs > 80;
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:

A history of other substance dependence (e.g., alcohol, opiates, sedative hypnotics), except for nicotine;
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);
A history of significant medical (e.g., cardiovascular, diabetic/metabolic) or neurological (e.g., cerebrovascular, seizure, traumatic brain injury) illness;
Current use of psychotropic and/or potentially psychoactive prescription medications;
Medical contraindications to participation in a magnetic resonance imaging procedure (e.g., ferromagnetic implants/foreign bodies, claustrophobia, cardiac pacemaker, prosthetic valve, otologic implant, etc.);
For females, laboratory (β-HCG) evidence of pregnancy, physical evidence of pregnancy;
For subjects interested in pharmacotherapy component, history of allergies to NAC and current elevation on liver function tests above twice the normal limit;
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;
Subjects with current, past or anticipated exposure to radiation in the work place within one year of proposed research PET scans;
History of a bleeding disorder or are currently taking anticoagulants (such as Coumadin, Heparin, Pradaxa, Xarelto);
Blood donation within eight weeks of the start of the study.

Sites / Locations

Connecticut Mental Health Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Active Comparator

Arm Label

1H MRS

[18F]-FDG PET scan

[11C]APP311 PET scan

Medication (NAC & placebo) administration

Arm Description

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

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.

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.

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.

Outcomes

Primary Outcome Measures

GLU and GLU/GLN ratios

Secondary Outcome Measures

Full Information

NCT ID

NCT02124941

First Posted

April 22, 2014

Last Updated

July 5, 2023

Sponsor

Yale University

Collaborators

National Institute on Drug Abuse (NIDA)

1. Study Identification

Unique Protocol Identification Number

NCT02124941

Brief Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Completed

Study Start Date

February 2014 (undefined)

Primary Completion Date

August 14, 2022 (Actual)

Study Completion Date

August 14, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Yale University

Collaborators

National Institute on Drug Abuse (NIDA)

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cocaine Dependence, Healthy

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

6 (Actual)

8. Arms, Groups, and Interventions

Arm Title

1H MRS

Arm Type

Experimental

Arm Description

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

Arm Title

[18F]-FDG PET scan

Arm Type

Experimental

Arm Description

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.

Arm Title

[11C]APP311 PET scan

Arm Type

Experimental

Arm Description

Arm Title

Medication (NAC & placebo) administration

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

N-acetyl cysteine

Intervention Description

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

Diagnostic Test

Intervention Name(s)

[18F]FDG PET scan

Intervention Description

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

Intervention Name(s)

1H MRS

Intervention Description

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

Intervention Name(s)

[11C]APP311 PET scan

Intervention Description

Primary Outcome Measure Information:

Title

GLU and GLU/GLN ratios

Time Frame

4 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age 18-55 years; Voluntary, written, informed consent; Physically healthy by medical history, physical, neurological, ECG and laboratory examinations; DSM-IV criteria for Cocaine Dependence (304.20) (Note: subjects will also meet DSM-5 criteria for Cocaine Use Disorder); 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) Full scale and verbal IQs > 80; 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: A history of other substance dependence (e.g., alcohol, opiates, sedative hypnotics), except for nicotine; 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); A history of significant medical (e.g., cardiovascular, diabetic/metabolic) or neurological (e.g., cerebrovascular, seizure, traumatic brain injury) illness; Current use of psychotropic and/or potentially psychoactive prescription medications; Medical contraindications to participation in a magnetic resonance imaging procedure (e.g., ferromagnetic implants/foreign bodies, claustrophobia, cardiac pacemaker, prosthetic valve, otologic implant, etc.); For females, laboratory (β-HCG) evidence of pregnancy, physical evidence of pregnancy; For subjects interested in pharmacotherapy component, history of allergies to NAC and current elevation on liver function tests above twice the normal limit; 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; Subjects with current, past or anticipated exposure to radiation in the work place within one year of proposed research PET scans; History of a bleeding disorder or are currently taking anticoagulants (such as Coumadin, Heparin, Pradaxa, Xarelto); Blood donation within eight weeks of the start of the study.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Gustavo Angarita, MD

Organizational Affiliation

Yale University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Connecticut Mental Health Center

City

New Haven

State/Province

Connecticut

ZIP/Postal Code

06519

Country

United States

12. IPD Sharing Statement

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

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