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Completed

NCT Number: NCT02124941

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

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.

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Key information

Age range

18 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Connecticut Mental Health Center

New Haven, Connecticut, 06519, United States

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

N-acetyl cysteine

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.

[18F]FDG PET scan

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.

1H MRS

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.

[11C]APP311 PET scan

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.

Primary outcomes

  1. GLU and GLU/GLN ratios

    Time frame: 4 weeks

Sponsors and collaborators

Lead sponsor

Yale University

Other

Collaborators

  • National Institute on Drug Abuse (NIDA)

Registry information

Important dates

Study start
2014
Primary completion
2022
Study completion
2022
First posted
Apr 28, 2014
Registry last updated
Jul 7, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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