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

Primary Purpose

Cocaine Use Disorder, Opioid Use Disorder

Status
Recruiting
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
n-acetylcysteine
Hydromorphone
Placebo n-acetylcystine
Placebo hydromorphone
Sponsored by
William Stoops
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Cocaine Use Disorder

Eligibility Criteria

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

Inclusion Criteria: Between the ages of 18 and 55 years, Report recent use of opioids and cocaine and must not be seeking treatment for their drug use, Be physically dependent on short-acting opioids, 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 Other than the diagnosis for opioid and cocaine use disorder at the time of the screening, subjects must be healthy, 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, No contraindications to magnetic resonance imagining (MRI; e.g., metallic objects in their body, BMI > or = 40, claustrophobia) will be considered ineligible, 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, All study subjects will be judged by the medical staff to be psychiatrically and physically healthy. Exclusion Criteria: 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, 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, Subjects who report a positive first-degree family history of schizophrenia, serious cardiovascular disease, or seizure disorders will also be excluded from research participation. Subjects with contraindications to hydromorphone or n-acetylcysteine will not be eligible.

Sites / Locations

  • University of Kentucky Laboratory of Human Behavioral PharmacologyRecruiting
  • University of Kentucky Department of Behavioral ScienceRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

n-Acetylcysteine

Placebo

Arm Description

Subjects will receive 0.6 g oral n-acetylcysteine 4 times per day.

Subjects will receive oral placebo 4 times per day.

Outcomes

Primary Outcome Measures

Hypothetical opioid purchasing
Amount of opioids purchased on a hypothetical purchase task
Hypothetical cocaine purchasing
Amount of cocaine purchased on a hypothetical purchase task
Glutamate function
Magnetic resonance spectroscopy of brain glutamate levels
Gamma Aminobutyric Acid (GABA) function
Magnetic resonance spectroscopy of brain GABA levels

Secondary Outcome Measures

Craving
Scores on a locally developed craving scale from 1-10, with higher scores indicating more craving
Subjective opioid withdrawal
Self-reported scores on the Subjective Opioid Withdrawal Scale with scores from 0-64, with higher scores indicating more withdrawal
Clinical opioid withdrawal
Self-reported scores on the Clinical Opioid Withdrawal Scale with scores from 0-48, with higher scores indicating more withdrawal

Full Information

First Posted
October 31, 2022
Last Updated
June 2, 2023
Sponsor
William Stoops
Collaborators
National Institute on Drug Abuse (NIDA)
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1. Study Identification

Unique Protocol Identification Number
NCT05610072
Brief Title
Behavioral Effects of Drugs (Inpatient): 43 (Opioids, Cocaine, n-Acetylcysteine)
Acronym
BED IN 43
Official Title
Glutamatergic Mechanisms in Opioid and Cocaine Co-Use
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 15, 2022 (Actual)
Primary Completion Date
December 31, 2026 (Anticipated)
Study Completion Date
December 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
William Stoops
Collaborators
National Institute on Drug Abuse (NIDA)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cocaine Use Disorder, Opioid Use Disorder

7. Study Design

Primary Purpose
Basic Science
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
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.
Masking
ParticipantCare ProviderOutcomes Assessor
Allocation
Randomized
Enrollment
24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
n-Acetylcysteine
Arm Type
Experimental
Arm Description
Subjects will receive 0.6 g oral n-acetylcysteine 4 times per day.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Subjects will receive oral placebo 4 times per day.
Intervention Type
Drug
Intervention Name(s)
n-acetylcysteine
Intervention Description
Subjects will be randomized to receive 2.4 oral n-acetylcysteine daily.
Intervention Type
Drug
Intervention Name(s)
Hydromorphone
Intervention Description
Subjects will receive up to 90 mg oral hydromorphone daily.
Intervention Type
Drug
Intervention Name(s)
Placebo n-acetylcystine
Intervention Description
Subjects will be randomized to receive placebo n-acetylcysteine daily.
Intervention Type
Drug
Intervention Name(s)
Placebo hydromorphone
Intervention Description
Prior to some experimental sessions, subjects will receive placebo hydromorphone
Primary Outcome Measure Information:
Title
Hypothetical opioid purchasing
Description
Amount of opioids purchased on a hypothetical purchase task
Time Frame
After at least seven days of maintenance on n-acetylcysteine or placebo
Title
Hypothetical cocaine purchasing
Description
Amount of cocaine purchased on a hypothetical purchase task
Time Frame
After at least seven days of maintenance on n-acetylcysteine or placebo
Title
Glutamate function
Description
Magnetic resonance spectroscopy of brain glutamate levels
Time Frame
After at least seven days of maintenance on n-acetylcysteine or placebo
Title
Gamma Aminobutyric Acid (GABA) function
Description
Magnetic resonance spectroscopy of brain GABA levels
Time Frame
After at least seven days of maintenance on n-acetylcysteine or placebo
Secondary Outcome Measure Information:
Title
Craving
Description
Scores on a locally developed craving scale from 1-10, with higher scores indicating more craving
Time Frame
After at least seven days of maintenance on n-acetylcysteine or placebo
Title
Subjective opioid withdrawal
Description
Self-reported scores on the Subjective Opioid Withdrawal Scale with scores from 0-64, with higher scores indicating more withdrawal
Time Frame
After at least seven days of maintenance on n-acetylcysteine or placebo
Title
Clinical opioid withdrawal
Description
Self-reported scores on the Clinical Opioid Withdrawal Scale with scores from 0-48, with higher scores indicating more withdrawal
Time Frame
After at least seven days of maintenance on n-acetylcysteine or placebo
Other Pre-specified Outcome Measures:
Title
Side effects
Description
Scores on the Udvalg Fur Kliniske Undersolgelser (UKU) side effects scale with scores from 0-3, with higher scores indicating greater side effects
Time Frame
Daily during approximately 10 day inpatient admission
Title
Pupil diameter
Description
Measurement of pupil diameter using an automated scanner
Time Frame
Daily during approximately 10 day inpatient admission
Title
Heart rate
Description
Measurement of heart rate using an automated monitor
Time Frame
Daily during approximately 10 day inpatient admission
Title
Respiration rate
Description
Measurement of respiration rate using an automated monitor
Time Frame
Daily during approximately 10 day inpatient admission
Title
Oxygen saturation
Description
Measurement of oxygen saturation using an automated monitor
Time Frame
Daily during approximately 10 day inpatient admission
Title
Diastolic blood pressure
Description
Measurement of diastolic blood pressure using an automated monitor
Time Frame
Daily during approximately 10 day inpatient admission
Title
Systolic blood pressure
Description
Measurement of systolic blood pressure using an automated monitor
Time Frame
Daily during approximately 10 day inpatient admission

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Between the ages of 18 and 55 years, Report recent use of opioids and cocaine and must not be seeking treatment for their drug use, Be physically dependent on short-acting opioids, 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 Other than the diagnosis for opioid and cocaine use disorder at the time of the screening, subjects must be healthy, 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, No contraindications to magnetic resonance imagining (MRI; e.g., metallic objects in their body, BMI > or = 40, claustrophobia) will be considered ineligible, 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, All study subjects will be judged by the medical staff to be psychiatrically and physically healthy. Exclusion Criteria: 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, 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, Subjects who report a positive first-degree family history of schizophrenia, serious cardiovascular disease, or seizure disorders will also be excluded from research participation. Subjects with contraindications to hydromorphone or n-acetylcysteine will not be eligible.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
William W Stoops, PhD
Phone
8592575388
Email
william.stoops@uky.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
William W Stoops
Organizational Affiliation
University of Kentucky
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Kentucky Laboratory of Human Behavioral Pharmacology
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40507
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
William W Stoops, Ph.D.
Phone
859-257-5388
Email
william.stoops@uky.edu
First Name & Middle Initial & Last Name & Degree
William W Stoops, Ph.D.
Facility Name
University of Kentucky Department of Behavioral Science
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536-0086
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
William W Stoops, Ph.D.
Phone
859-257-5388
Email
william.stoops@uky.edu
First Name & Middle Initial & Last Name & Degree
William W Stoops, Ph.D.

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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