Behavioral Effects of Drugs (Inpatient): 43 (Opioids, Cocaine, n-Acetylcysteine)

Opioid Use Disorder Clinical Trial

— BED IN 43  

Official title:

Glutamatergic Mechanisms in Opioid and Cocaine Co-Use

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05610072
• Other study ID #: 80485
• Secondary ID: R33DA049130
• Status: Recruiting
• Phase: Early Phase 1
• Start date: December 15, 2022
• Est. completion date: December 31, 2026

Study information

• Verified date: June 2024
• Source: University of Kentucky
• Contact: William W Stoops, PhD
• Phone: 8592575388
• Email: william.stoops[@]uky.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cocaine Use Disorder
• Opioid Use Disorder
• Opioid-Related Disorders

Intervention

Drug:
• n-acetylcysteine
Subjects will be randomized to receive 2.4 oral n-acetylcysteine daily.
• Hydromorphone
Subjects will receive up to 192 mg oral hydromorphone daily.
• Placebo n-acetylcystine
Subjects will be randomized to receive placebo n-acetylcysteine daily.
• Placebo hydromorphone
Prior to some experimental sessions, subjects will receive placebo hydromorphone

Locations

Country	Name	City	State
United States	University of Kentucky Department of Behavioral Science	Lexington	Kentucky
United States	University of Kentucky Laboratory of Human Behavioral Pharmacology	Lexington	Kentucky

Sponsors (2)

Lead Sponsor	Collaborator
William Stoops	National Institute on Drug Abuse (NIDA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Side effects	Scores on the Udvalg Fur Kliniske Undersolgelser (UKU) side effects scale with scores from 0-3, with higher scores indicating greater side effects	Daily during approximately 10 day inpatient admission
Other	Pupil diameter	Measurement of pupil diameter using an automated scanner	Daily during approximately 10 day inpatient admission
Other	Heart rate	Measurement of heart rate using an automated monitor	Daily during approximately 10 day inpatient admission
Other	Respiration rate	Measurement of respiration rate using an automated monitor	Daily during approximately 10 day inpatient admission
Other	Oxygen saturation	Measurement of oxygen saturation using an automated monitor	Daily during approximately 10 day inpatient admission
Other	Diastolic blood pressure	Measurement of diastolic blood pressure using an automated monitor	Daily during approximately 10 day inpatient admission
Other	Systolic blood pressure	Measurement of systolic blood pressure using an automated monitor	Daily during approximately 10 day inpatient admission
Primary	Hypothetical opioid purchasing	Amount of opioids purchased on a hypothetical purchase task	After at least seven days of maintenance on n-acetylcysteine or placebo
Primary	Hypothetical cocaine purchasing	Amount of cocaine purchased on a hypothetical purchase task	After at least seven days of maintenance on n-acetylcysteine or placebo
Primary	Glutamate function	Magnetic resonance spectroscopy of brain glutamate levels	After at least seven days of maintenance on n-acetylcysteine or placebo
Primary	Gamma Aminobutyric Acid (GABA) function	Magnetic resonance spectroscopy of brain GABA levels	After at least seven days of maintenance on n-acetylcysteine or placebo
Secondary	Craving	Scores on a locally developed craving scale from 1-10, with higher scores indicating more craving	After at least seven days of maintenance on n-acetylcysteine or placebo
Secondary	Subjective opioid withdrawal	Self-reported scores on the Subjective Opioid Withdrawal Scale with scores from 0-64, with higher scores indicating more withdrawal	After at least seven days of maintenance on n-acetylcysteine or placebo
Secondary	Clinical opioid withdrawal	Self-reported scores on the Clinical Opioid Withdrawal Scale with scores from 0-48, with higher scores indicating more withdrawal	After at least seven days of maintenance on n-acetylcysteine or placebo