Back to resultsThe Role of Neuroactive Steroids in Stress, Drug Craving and Drug Use in Cocaine Use Disorders
Primary Purpose
Cocaine-Related Disorders
Status
Recruiting
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
PREG 300/500 mg
Placebos
Sponsored by
About this trial
This is an interventional treatment trial for Cocaine-Related Disorders
Eligibility Criteria
Inclusion Criteria:
- Male or female individuals, ages 18 to 60.
- Subjects must meet current DSM-V criteria for cocaine use disorder; documented positive urine toxicology screen for cocaine at intake or collateral information from family members, significant others, room-mates etc., on recent use.
- Subject has voluntarily given informed consent and signed the informed consent document.
- Able to read English and complete study evaluations.
Exclusion Criteria:
- Women who are pregnant, or nursing or are of childbearing potential and not practicing an effective means of birth control.
- Meet current criteria for use disorder on another psychoactive substance, such as, heroin, amphetamines, hallucinogens/PCP, excluding alcohol and nicotine.
- Any current use of opiates or past history of opiate use disorder.
- Current use of any psychoactive drugs, including anxiolytics, antidepressants, naltrexone or antabuse.
- Any psychotic disorder or current Axis I psychiatric symptoms requiring specific attention, including need for psychiatric medications for current major depression and anxiety disorders.
- Significant underlying medical conditions such as cerebral, renal, thyroid or cardiac pathology which in the opinion of study physician would preclude patient from fully cooperating or be of potential harm during the course of the study.
- Abstinent from cocaine for more than two weeks prior to admission.
- Hypotensive individuals with sitting blood pressure below 90/50 mmHG.
Sites / Locations
- Yale Stress CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
patients receiving PREG
patients receiving placebo
Arm Description
Eligible participants will be randomly assigned to 2 doses of PREG (300/500 mg/day) over 8 weeks with a) an inpatient-outpatient option where they will be admitted to the Clinical Neuroscience Research Unit (CNRU) at the Connecticut Mental Health Center (CMHC) for first two weeks and then outpatient at Yale Stress Center (YSC) for the remaining 6 weeks, or b) an outpatient option where they will participate in the entire study outpatient at YSC.
Eligible participants will be randomly assigned to a placebo (PLA) treatment over 8 weeks with a) an inpatient-outpatient option where they will be admitted to the Clinical Neuroscience Research Unit (CNRU) at the Connecticut Mental Health Center (CMHC) for the first two weeks and then transition to outpatient at Yale Stress Center (YSC) for the remaining 6 weeks, or b) an outpatient only option where they will participate in the entire study outpatient at YSC.
Outcomes
Primary Outcome Measures
Craving reactivity in the laboratory
Cocaine craving assessed in laboratory experiment with exposure to stress, drug cues and neutral control condition in week 2 of PREG (300mg; 500mg) vs. Placebo treatment. Cocaine craving will be assessed using a 10-point visual analog scale (VAS) in which 0="not at all" and 10="extremely high".
Plasma cortisol levels as a measure of stress response in the laboratory
Plasma will be collected at each laboratory session to assess cortisol response to stress, drug cue and neutral imagery exposure.
Blood pressure responses in the laboratory
A General Electric Dynamap will be used to place a blood pressure cuff on the subject's preferred arm to monitor blood pressure (BP) during the laboratory sessions in week 2 in order to assess change in BP responses to stress, drug cue and neutral provocation.
Heart rate beats per minutes responses in the laboratory
A General Electric Dynamap will be used to place a blood pressure cuff on the subject's preferred arm to monitor heart rate (HR) beats per minutes during the laboratory sessions in week 2 in order to assess change in HR responses to stress, drug cue and neutral provocation.
Provoked negative emotion and anxiety
Differential Emotion Scale (DES) will be used to measure subjective emotion. During the laboratory sessions, subjects will be asked to rate their current emotional state for the following subscales: anger, fear, sadness, anxiety, joy, neutral-relaxed feelings. Each subscale includes five adjectives (a total of 30 items) and will be used to describe each affect state and subjects are required to rate on a 5-point scale the extent to which each word describes the way s/he feels at the present time.
Provoked cognitive flexibility
Stroop Color Word Test during stress, drug cue and neutral provocation
Area under the curve (Pharmacokinetic Profile )
To examine the blood plasma levels of two doses of PREG (300mg; 500mg; bid), and matching placebo (PLA) will be assessed over a 24 hour period and area under the curve will be plotted as drug concentration over time.
Maximum Plasma Concentration (Cmax); Pharmacokinetic Profile
The maximum (peak) plasma concentration achieved after two doses of PREG (300mg;500mg; bid) will be calculated.
Plasma Half-Life (t1/2) of Pregnenolone
The half-life of two doses of PREG (300mg; 500mg; bid), and matching placebo (PLA) will be calculated as the time it takes for the blood plasma concentration of PREG to halve its steady-state.
Change from baseline Adverse Events
The Systematic Assessment for Treatment Emergent Effects (SAFTEE) Questionnaire will be used to assess the change from baseline adverse events weekly during the trial.
Secondary Outcome Measures
Cocaine use as secondary clinical outcome using urine toxicology.
Percent of positive urine tests during the 8 week trial will be assessed by a weekly urine toxicology screening.
Cocaine use amount as secondary clinical outcome using Timeline Followback Substance Use Calendar.
Change compared to baseline in daily reporting of amount of cocaine per use day will be assessed by self report on the Timeline Followback Substance Use Calendar.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03953612
Brief Title
The Role of Neuroactive Steroids in Stress, Drug Craving and Drug Use in Cocaine Use Disorders
Official Title
The Role of Neuroactive Steroids in Stress, Drug Craving and Drug Use in Cocaine Use Disorders
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 12, 2019 (Actual)
Primary Completion Date
February 2024 (Anticipated)
Study Completion Date
February 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Yale University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
To use pregnenolone (PREG; 300; 500mg) daily versus placebo (PLA) as a probe to assess the role of neuroactive steroids in individuals with cocaine use disorder (CUD).
Detailed Description
This experimental study aims to examine the effects of PREG on a) repeated cocaine craving, mood and neurobiological reactivity to brief, guided imagery exposure to stress, drug cues and neutral situations in the laboratory and b) daily cocaine intake, craving, cognition and mood in men and women with CUD; and c) sex differences in all of these outcomes. The study's hypothesis is that PREG vs PLA will dose-specifically decrease stress-induced and drug-cue induced cocaine craving, improve mood and cognitive performance, and normalize hypothalamic pituitary adrenal (HPA) axis response to stress and drug-cue imagery, and reduce cocaine intake and craving in daily life in individuals with CUD.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cocaine-Related Disorders
7. Study Design
Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Model Description
Eligible participants will be randomly assigned to 2 doses of PREG (300/500 mg/day) vs placebo (PLA) treatment (N=20/group) over 8 weeks.
Masking
Participant
Allocation
Randomized
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
patients receiving PREG
Arm Type
Experimental
Arm Description
Eligible participants will be randomly assigned to 2 doses of PREG (300/500 mg/day) over 8 weeks with a) an inpatient-outpatient option where they will be admitted to the Clinical Neuroscience Research Unit (CNRU) at the Connecticut Mental Health Center (CMHC) for first two weeks and then outpatient at Yale Stress Center (YSC) for the remaining 6 weeks, or b) an outpatient option where they will participate in the entire study outpatient at YSC.
Arm Title
patients receiving placebo
Arm Type
Placebo Comparator
Arm Description
Eligible participants will be randomly assigned to a placebo (PLA) treatment over 8 weeks with a) an inpatient-outpatient option where they will be admitted to the Clinical Neuroscience Research Unit (CNRU) at the Connecticut Mental Health Center (CMHC) for the first two weeks and then transition to outpatient at Yale Stress Center (YSC) for the remaining 6 weeks, or b) an outpatient only option where they will participate in the entire study outpatient at YSC.
Intervention Type
Drug
Intervention Name(s)
PREG 300/500 mg
Intervention Description
2 doses of PREG (300/500 mg/day)
Intervention Type
Drug
Intervention Name(s)
Placebos
Intervention Description
placebo
Primary Outcome Measure Information:
Title
Craving reactivity in the laboratory
Description
Cocaine craving assessed in laboratory experiment with exposure to stress, drug cues and neutral control condition in week 2 of PREG (300mg; 500mg) vs. Placebo treatment. Cocaine craving will be assessed using a 10-point visual analog scale (VAS) in which 0="not at all" and 10="extremely high".
Time Frame
in week 2 of treatment
Title
Plasma cortisol levels as a measure of stress response in the laboratory
Description
Plasma will be collected at each laboratory session to assess cortisol response to stress, drug cue and neutral imagery exposure.
Time Frame
in week 2 of treatment
Title
Blood pressure responses in the laboratory
Description
A General Electric Dynamap will be used to place a blood pressure cuff on the subject's preferred arm to monitor blood pressure (BP) during the laboratory sessions in week 2 in order to assess change in BP responses to stress, drug cue and neutral provocation.
Time Frame
in week 2 of treatment
Title
Heart rate beats per minutes responses in the laboratory
Description
A General Electric Dynamap will be used to place a blood pressure cuff on the subject's preferred arm to monitor heart rate (HR) beats per minutes during the laboratory sessions in week 2 in order to assess change in HR responses to stress, drug cue and neutral provocation.
Time Frame
in week 2 of treatment
Title
Provoked negative emotion and anxiety
Description
Differential Emotion Scale (DES) will be used to measure subjective emotion. During the laboratory sessions, subjects will be asked to rate their current emotional state for the following subscales: anger, fear, sadness, anxiety, joy, neutral-relaxed feelings. Each subscale includes five adjectives (a total of 30 items) and will be used to describe each affect state and subjects are required to rate on a 5-point scale the extent to which each word describes the way s/he feels at the present time.
Time Frame
in week 2 of treatment
Title
Provoked cognitive flexibility
Description
Stroop Color Word Test during stress, drug cue and neutral provocation
Time Frame
in week 2 of treatment
Title
Area under the curve (Pharmacokinetic Profile )
Description
To examine the blood plasma levels of two doses of PREG (300mg; 500mg; bid), and matching placebo (PLA) will be assessed over a 24 hour period and area under the curve will be plotted as drug concentration over time.
Time Frame
in week 2 of treatment
Title
Maximum Plasma Concentration (Cmax); Pharmacokinetic Profile
Description
The maximum (peak) plasma concentration achieved after two doses of PREG (300mg;500mg; bid) will be calculated.
Time Frame
in week 2 of treatment
Title
Plasma Half-Life (t1/2) of Pregnenolone
Description
The half-life of two doses of PREG (300mg; 500mg; bid), and matching placebo (PLA) will be calculated as the time it takes for the blood plasma concentration of PREG to halve its steady-state.
Time Frame
in week 2 of treatment
Title
Change from baseline Adverse Events
Description
The Systematic Assessment for Treatment Emergent Effects (SAFTEE) Questionnaire will be used to assess the change from baseline adverse events weekly during the trial.
Time Frame
at week 8
Secondary Outcome Measure Information:
Title
Cocaine use as secondary clinical outcome using urine toxicology.
Description
Percent of positive urine tests during the 8 week trial will be assessed by a weekly urine toxicology screening.
Time Frame
weekly during 8 weeks
Title
Cocaine use amount as secondary clinical outcome using Timeline Followback Substance Use Calendar.
Description
Change compared to baseline in daily reporting of amount of cocaine per use day will be assessed by self report on the Timeline Followback Substance Use Calendar.
Time Frame
weekly during 8 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female individuals, ages 18 to 60.
Subjects must meet current DSM-V criteria for cocaine use disorder; documented positive urine toxicology screen for cocaine at intake or collateral information from family members, significant others, room-mates etc., on recent use.
Subject has voluntarily given informed consent and signed the informed consent document.
Able to read English and complete study evaluations.
Exclusion Criteria:
Women who are pregnant, or nursing or are of childbearing potential and not practicing an effective means of birth control.
Meet current criteria for use disorder on another psychoactive substance, such as, heroin, amphetamines, hallucinogens/PCP, excluding alcohol and nicotine.
Any current use of opiates or past history of opiate use disorder.
Current use of any psychoactive drugs, including anxiolytics, antidepressants, naltrexone or antabuse.
Any psychotic disorder or current Axis I psychiatric symptoms requiring specific attention, including need for psychiatric medications for current major depression and anxiety disorders.
Significant underlying medical conditions such as cerebral, renal, thyroid or cardiac pathology which in the opinion of study physician would preclude patient from fully cooperating or be of potential harm during the course of the study.
Abstinent from cocaine for more than two weeks prior to admission.
Hypotensive individuals with sitting blood pressure below 90/50 mmHG.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Verica Milivojevic, PhD
Phone
203-737-5201
Email
verica.milivojevic@yale.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Julie Pinto, MS
Phone
203-737-5489
Email
julie.pinto@yale.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Verica Milivojevic, PhD
Organizational Affiliation
Yale University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Yale Stress Center
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06519
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rachel L Hart, MS
Phone
203-737-4791
Email
rachel.hart@yale.edu
First Name & Middle Initial & Last Name & Degree
Verica Milivojevic, PhD
12. IPD Sharing Statement
Learn more about this trial
The Role of Neuroactive Steroids in Stress, Drug Craving and Drug Use in Cocaine Use Disorders
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