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CompletedNCT03953612Updated Jul 3, 2024Results posted

The Role of Neuroactive Steroids in Stress, Drug Craving and Drug Use in Cocaine Use Disorders

An Early Phase 1 interventional study of Pregnenolone (PREG) and Placebos in Cocaine-Related Disorders, sponsored by Yale University. Completed at 1 site in United States. Open to participants aged 18 Years to 60 Years. Per ClinicalTrials.gov, last updated 2024-07-03.

Sponsored by Yale University · Early Phase 1, Interventional, and Treatment

Phase
Early Phase 1
Study type
Interventional
Enrollment
58
Allocation
Randomized
Ages
18 Years to 60 Years
Sex
All
01

Study 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).

Read the 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.

02

Conditions studied

  • Cocaine-Related Disorders
03

In context

Cocaine-Related Disorders

415 studies on the registry are indexed under Cocaine-Related Disorders; 12 are open to participants now.

This study's enrollment of 58 is close to the median of 60 across 312 interventional studies indexed under Cocaine-Related Disorders.

Browse Cocaine-Related Disorders studies →

Lead sponsor

Yale University is the lead sponsor of 1,724 studies on the registry; 298 are open to participants now.

Of its 210 completed or terminated interventional studies of FDA-regulated products, 126 (60%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 60 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
05

Study design

Phase
Early Phase 1
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Single (Participant)
Enrollment
58 participants (actual)

Study arms

  • Experimental
    PREG 300

    Eligible participants will be randomly assigned to PREG 300 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.

    Drug: Pregnenolone (PREG)

  • Placebo comparator
    patients receiving placebo

    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.

    Drug: Placebos

  • Experimental
    PREG 500

    Eligible participants will be randomly assigned to PREG 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.

    Drug: Pregnenolone (PREG)

Interventions

  • DrugPregnenolone (PREG)

    2 doses of PREG (300 or 500 mg/day)

  • DrugPlacebos

    placebo

06

What researchers measure

Primary outcomes

  1. Craving Change in Stress and Cue Relative to Neutral

    Cocaine craving assessed in a laboratory experiment with exposure to stress, cocaine cue and neutral control condition in those receiving PREG (300mg; 500mg) vs Placebo. Cocaine craving was assessed using the Cocaine Craving Questionnaire (CCQ), a brief 10-item self-report craving scale that ranges in mean score from 1 to 7, where a higher score indicates higher craving. Data presented here is craving change in stress relative to neutral and craving change in cue relative to neutral, where the possible range in mean change score is -6 to +6.

    Time frame: Experiment during treatment week 2

Secondary outcomes

  1. Anxiety Change in Stress and Cue Relative to Neutral

    Anxiety assessed in laboratory experiment with exposure to stress, cocaine cue and neutral control condition in participants receiving PREG (300mg; 500mg) vs. Placebo treatment. Anxiety was assessed using a 10-point visual analog scale (VAS) in which 0="not at all" and 10="extremely high", with the mean score ranging from 0 to 10, and where higher score means higher anxiety. Data presented here is anxiety change in stress relative to neutral and anxiety change in cue relative to neutral, where the possible range in mean change score is -10 to +10.

    Time frame: Experiment during treatment week 2

  2. Cortisol Level Change in Stress and Cue Relative to Neutral

    Plasma was collected at each laboratory session to measure cortisol level and assess change in cortisol response to stress and cocaine cue relative neutral imagery condition exposure. Data presented here are change in cortisol level (mg/dl) in stress relative to neutral condition and cue relative to neutral condition.

    Time frame: Experiment during treatment week 2

  3. Pregnenolone Concentration

    Blood plasma concentration of pregnenolone in two doses of PREG (300mg; 500mg), and matching placebo, assessed over a 24 hour period.

    Time frame: between weeks 2-3 of treatment

Other outcomes

  1. Cocaine Dollar Amount During Trial Period

    Mean dollar amount of cocaine per use day was assessed by daily self report on the Timeline Followback Substance Use Calendar and corroborated by daily self-reporting on smartphone (measurement unit in dollars).

    Time frame: up to 8 weeks

  2. Mean Percent Cocaine Days

    The mean percent cocaine days as assessed by self report on daily smartphone monitoring and corroborated by the Timeline Followback Substance Use Calendar over the 8 week period.

    Time frame: up to 8 weeks

07

Results

Posted Jul 3, 2024

Participant flow

Participant flow — Overall Study
MilestonePREG 300 mg/DayPREG 500 mg/DayPatients Receiving Placebo
Started211819
Intent to treat sample included in analyses201718
Dropout weeks 1-3110
Dropout weeks 4-12100
Completed181618
Not completed321
Withdrew: Randomized but did not start111
Withdrew: Withdrawal by subject210

Outcome measures

PrimaryCraving Change in Stress and Cue Relative to Neutral

Cocaine craving assessed in a laboratory experiment with exposure to stress, cocaine cue and neutral control condition in those receiving PREG (300mg; 500mg) vs Placebo. Cocaine craving was assessed using the Cocaine Craving Questionnaire (CCQ), a brief 10-item self-report craving scale that ranges in mean score from 1 to 7, where a higher score indicates higher craving. Data presented here is craving change in stress relative to neutral and craving change in cue relative to neutral, where the possible range in mean change score is -6 to +6.

Time frame:
Experiment during treatment week 2
Reported as:
Mean · score on a scale
Craving Change in Stress and Cue Relative to Neutral
score on a scalePREG 300 mg/DayPREG 500 mg/DayPatients Receiving Placebo
Stress Craving Change3.035 ± 1.34-0.486 ± 1.1533.959 ± 1.115
Cue Craving Change0.031 ± 1.313-1.775 ± 1.1264.835 ± 1.118
Statistical analysis
  • PREG 300 mg/Day vs PREG 500 mg/Day vs Patients Receiving Placebo · Mixed Models Analysis · p = <.001Linear mixed effects
SecondaryAnxiety Change in Stress and Cue Relative to Neutral

Anxiety assessed in laboratory experiment with exposure to stress, cocaine cue and neutral control condition in participants receiving PREG (300mg; 500mg) vs. Placebo treatment. Anxiety was assessed using a 10-point visual analog scale (VAS) in which 0="not at all" and 10="extremely high", with the mean score ranging from 0 to 10, and where higher score means higher anxiety. Data presented here is anxiety change in stress relative to neutral and anxiety change in cue relative to neutral, where the possible range in mean change score is -10 to +10.

Time frame:
Experiment during treatment week 2
Reported as:
Mean · score on a scale
Anxiety Change in Stress and Cue Relative to Neutral
score on a scalePREG 300 mg/DayPREG 500 mg/DayPatients Receiving Placebo
Stress Anxiety Change0.757 ± 0.3090.118 ± 0.2691.334 ± 0.263
Cue Anxiety Change-0.305 ± 0.3020.199 ± 0.2610.959 ± 0.265
Statistical analysis
  • PREG 300 mg/Day vs PREG 500 mg/Day vs Patients Receiving Placebo · Mixed Models Analysis · p = <.001Linear mixed effects
SecondaryCortisol Level Change in Stress and Cue Relative to Neutral

Plasma was collected at each laboratory session to measure cortisol level and assess change in cortisol response to stress and cocaine cue relative neutral imagery condition exposure. Data presented here are change in cortisol level (mg/dl) in stress relative to neutral condition and cue relative to neutral condition.

Time frame:
Experiment during treatment week 2
Reported as:
Mean · mg/dl
Cortisol Level Change in Stress and Cue Relative to Neutral
mg/dlPREG 300 mg/DayPREG 500 mg/DayPatients Receiving Placebo
Stress Cortisol Level Change-0.3 ± 0.55-0.52 ± 0.640.71 ± 0.9
Cue Cortisol Level Change0 ± 0.45-0.07 ± 0.730.58 ± 0.67
Statistical analysis
  • PREG 300 mg/Day vs PREG 500 mg/Day vs Patients Receiving Placebo · Mixed Models Analysis · p = 0.7Linear mixed effects
SecondaryPregnenolone Concentration

Blood plasma concentration of pregnenolone in two doses of PREG (300mg; 500mg), and matching placebo, assessed over a 24 hour period.

Time frame:
between weeks 2-3 of treatment
Reported as:
Mean · ng/mL
Pregnenolone Concentration
ng/mLPREG 300 mg/DayPREG 500 mg/DayPatients Receiving Placebo
Pregnenolone Concentration1.09 ± 0.1941.54 ± 0.1470.5 ± 0.146
Statistical analysis
  • PREG 300 mg/Day vs PREG 500 mg/Day vs Patients Receiving Placebo · ANOVA · p = 0.0001
Other pre-specifiedCocaine Dollar Amount During Trial Period

Mean dollar amount of cocaine per use day was assessed by daily self report on the Timeline Followback Substance Use Calendar and corroborated by daily self-reporting on smartphone (measurement unit in dollars).

Time frame:
up to 8 weeks
Reported as:
Mean · dollars
Cocaine Dollar Amount During Trial Period
dollarsPREG 300 mg/DayPREG 500 mg/DayPatients Receiving Placebo
Cocaine Dollar Amount During Trial Period12.3 ± 17.5726.44 ± 20.5928.28 ± 43.99
Statistical analysis
  • PREG 300 mg/Day vs PREG 500 mg/Day vs Patients Receiving Placebo · . Negative binomial regression models · p = 0.042
Other pre-specifiedMean Percent Cocaine Days

The mean percent cocaine days as assessed by self report on daily smartphone monitoring and corroborated by the Timeline Followback Substance Use Calendar over the 8 week period.

Time frame:
up to 8 weeks
Reported as:
Mean · percent days
Mean Percent Cocaine Days
percent daysPREG 300 mg/DayPREG 500 mg/DayPatients Receiving Placebo
Mean Percent Cocaine Days19.9 ± 20.4635.12 ± 20.0528.61 ± 26.19
Statistical analysis
  • PREG 300 mg/Day vs PREG 500 mg/Day vs Patients Receiving Placebo · . Negative binomial regression models · p = 0.125

Adverse events

Collected over up to 8 weeks. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
PREG 300 mg/Day0/20 (0%)1/20 (5%)12/20 (60%)
PREG 500 mg/Day0/17 (0%)0/17 (0%)13/17 (76.5%)
Patients Receiving Placebo0/18 (0%)0/18 (0%)11/18 (61.1%)
Most frequent serious events
Most frequent serious events
EventPREG 300 mg/DayPREG 500 mg/DayPatients Receiving Placebo
DizzinessNervous system disorders1/200/170/18
Most frequent other events
Most frequent other events
EventPREG 300 mg/DayPREG 500 mg/DayPatients Receiving Placebo
Injury/PainGeneral disorders5/203/172/18
Infection/Immune SystemGeneral disorders2/203/171/18
HeadacheNervous system disorders2/202/173/18
Psychiatric disorders - Other, specifyPsychiatric disorders0/202/171/18
Gastrointestinal disorders - Other, specifyGastrointestinal disorders1/201/171/18
Inflammation/AllergyGeneral disorders1/201/171/18
FatigueGeneral disorders0/201/171/18
Suicidal ThoughtsPsychiatric disorders0/200/171/18
LightheadednessNervous system disorders1/200/170/18

Baseline characteristics

Age, Continuous
Age, Continuous(years)PREG 300 mg/DayPREG 500 mg/DayPatients Receiving PlaceboTotal
Mean48.05 ± 11.3146.47 ± 11.0647.17 ± 9.4447.27 ± 10.48
Sex: Female, Male
Sex: Female, Male(Participants)PREG 300 mg/DayPREG 500 mg/DayPatients Receiving PlaceboTotal
Female55616
Male15121239
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)PREG 300 mg/DayPREG 500 mg/DayPatients Receiving PlaceboTotal
Hispanic or Latino0325
Not Hispanic or Latino20141650
Unknown or Not Reported0000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)PREG 300 mg/DayPREG 500 mg/DayPatients Receiving PlaceboTotal
American Indian or Alaska Native0000
Asian0000
Native Hawaiian or Other Pacific Islander0000
Black or African American1410933
White46919
More than one race0000
Unknown or Not Reported2103
Region of Enrollment
Region of Enrollment(participants)PREG 300 mg/DayPREG 500 mg/DayPatients Receiving PlaceboTotal
United States20171855
Years of Education
Years of Education(years)PREG 300 mg/DayPREG 500 mg/DayPatients Receiving PlaceboTotal
Mean12.5 ± 1.412.35 ± 1.8712.56 ± 1.5812.47 ± 1.59
Number of Smokers
Number of Smokers(Participants)PREG 300 mg/DayPREG 500 mg/DayPatients Receiving PlaceboTotal
Count of participants14141644
08

Study locations

1 site
  • Yale Stress Center
    New Haven, Connecticut 06519, United States
09

References and documents

Study documents

  • Protocol and statistical analysis plan · Mar 3, 2023
  • Informed consent form · Nov 10, 2021

Documents are hosted by the registry — open the source record to download them.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jul 3, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03953612
Lead sponsor
Yale University
Collaborators
National Institute on Drug Abuse (NIDA)
Responsible party
Sponsor
First posted
May 16, 2019
Start date
Mar 12, 2019
Primary completion
May 8, 2023
Completion
May 8, 2023
Results posted
Jul 3, 2024
Last update
Jul 3, 2024

Study contacts

Verica Milivojevic, PhD
principal investigator · Yale University

Oversight

FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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