Clinical trial NCT05610072: Behavioral Effects of Drugs (Inpatient): 43 (Opioids, Cocaine, n-Acetylcysteine)
Official title: Glutamatergic Mechanisms in Opioid and Cocaine Co-Use
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Cocaine Use Disorder
Opioid Use Disorder
Lead sponsor: University of Kentucky
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2022-11-09
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study will use a double-blind, placebo-controlled design with all subjects receiving all hydromorphone (i.e., hydromorphone dose is a within subject factors). Half of the subjects will receive placebo and half of the subjects will receive 2.4mg/day NAC.
Primary purpose: BASIC_SCIENCE

Brief summary: The overarching hypotheses of this protocol are that (1) persistent brain glutamate changes induced by chronic opioid use will exacerbate use of cocaine during opioid physical dependence and withdrawal and (2) n-acetylcysteine (NAC) will ameliorate glutamatergic dysregulation, and thus will reduce both opioid and cocaine demand. These hypotheses will be tested with two specific aims.

Specific Aim 1. Determine the reinforcing effects of cocaine in individuals with comorbid opioid and cocaine use disorder with physiological dependence on opioids during NAC maintenance. All subjects will be maintained on oral hydromorphone. They will also be randomly assigned to receive placebo or oral NAC (2.4 g/day), stratified by sex. After dose stabilization, experimental sessions will be conducted in which subjects complete hypothetical cocaine purchase tasks during opioid maintenance and opioid withdrawal. The hypotheses are: 1) cocaine purchasing will be greater during opioid withdrawal and 2) NAC maintenance will attenuate cocaine purchasing across opioid maintenance and withdrawal periods.

Specific Aim 2. Evaluate glutamate functionality during periods of opioid maintenance and withdrawal in individuals with comorbid opioid and cocaine use disorder and physiological dependence on opioids during NAC maintenance. Subjects will undergo magnetic resonance spectroscopy to evaluate brain glutamate changes as a function of opioid maintenance/withdrawal state and NAC maintenance. The hypotheses are: 1) glutamate levels will be elevated during opioid withdrawal and 2) NAC maintenance will ameliorate elevated glutamate levels.


Eligibility criteria: Inclusion Criteria:

1. Between the ages of 18 and 55 years,
2. Report recent use of opioids and cocaine and must not be seeking treatment for their drug use,
3. Be physically dependent on short-acting opioids,
4. Meet Diagnostic and Statistical Manual (DSM)-5 diagnostic criteria for current opioid use disorder (OUD) and current or past cocaine use disorder (CUD) and have either a urine sample positive for recent opioid use during each visit or if opioid negative, displaying frank withdrawal during screening
5. Other than the diagnosis for opioid and cocaine use disorder at the time of the screening, subjects must be healthy,
6. Laboratory chemistries (e.g., blood chemistry screen, complete blood count, urinalysis) and electrocardiogram (ECG) results must be normal or within normal range and any abnormal results must be considered as not clinically significant by the study physicians,
7. No contraindications to magnetic resonance imagining (MRI; e.g., metallic objects in their body, BMI \> or = 40, claustrophobia) will be considered ineligible,
8. Female subjects must be using an effective form of birth control (e.g., birth control pills, surgical sterilization, intrauterine device, barrier method, condoms with spermicide, cervical cap with a spermicide or abstinence) to participate and must not be pregnant,
9. All study subjects will be judged by the medical staff to be psychiatrically and physically healthy.

Exclusion Criteria:

1. Any potential subject with a history of serious physical disease, current physical disease (e.g., impaired cardiovascular functioning, histories of seizure, head trauma, diabetes, asthma, or central nervous system \[CNS\] tumors) or current or past histories of serious psychiatric disorder (e.g., schizophrenia) that would limit compliance in the study, other than substance use disorder, will be excluded from research participation,
2. Potential subjects that meet diagnostic criteria for moderate - severe substance use disorder for substances other than opioids, stimulants, cannabis, or nicotine at the time of the interview will not be eligible for study participation,
3. Subjects who report a positive first-degree family history of schizophrenia, serious cardiovascular disease, or seizure disorders will also be excluded from research participation.
4. Subjects with contraindications to hydromorphone or n-acetylcysteine will not be eligible.

Primary outcomes:
measure: Hypothetical opioid purchasing
timeFrame: After at least seven days of maintenance on n-acetylcysteine or placebo
measure: Hypothetical cocaine purchasing
timeFrame: After at least seven days of maintenance on n-acetylcysteine or placebo
measure: Glutamate function
timeFrame: After at least seven days of maintenance on n-acetylcysteine or placebo
measure: Gamma Aminobutyric Acid (GABA) function
timeFrame: After at least seven days of maintenance on n-acetylcysteine or placebo
Secondary outcomes:
measure: Craving
timeFrame: After at least seven days of maintenance on n-acetylcysteine or placebo
measure: Subjective opioid withdrawal
timeFrame: After at least seven days of maintenance on n-acetylcysteine or placebo
measure: Clinical opioid withdrawal
timeFrame: After at least seven days of maintenance on n-acetylcysteine or placebo
Other outcomes:
measure: Side effects
timeFrame: Daily during approximately 10 day inpatient admission
measure: Pupil diameter
timeFrame: Daily during approximately 10 day inpatient admission
measure: Heart rate
timeFrame: Daily during approximately 10 day inpatient admission
measure: Respiration rate
timeFrame: Daily during approximately 10 day inpatient admission
measure: Oxygen saturation
timeFrame: Daily during approximately 10 day inpatient admission
measure: Diastolic blood pressure
timeFrame: Daily during approximately 10 day inpatient admission
measure: Systolic blood pressure
timeFrame: Daily during approximately 10 day inpatient admission
Locations:
city: Lexington
country: United States
facility: University of Kentucky Laboratory of Human Behavioral Pharmacology
state: Kentucky
city: Lexington
country: United States
facility: University of Kentucky Department of Behavioral Science
state: Kentucky
Study officials:
affiliation: University of Kentucky
name: William W Stoops
role: PRINCIPAL_INVESTIGATOR
References: