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

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).

Study Overview

• Status: Completed
• Conditions: Cocaine-Related Disorders
• Intervention / Treatment: Drug: Placebos; Drug: Pregnenolone (PREG)

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.

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale Stress Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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; placebo
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); 2 doses of PREG (300 or 500 mg/day)
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); 2 doses of PREG (300 or 500 mg/day)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Experiment during treatment week 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Experiment during treatment week 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.	Experiment during treatment week 2
Pregnenolone Concentration	Blood plasma concentration of pregnenolone in two doses of PREG (300mg; 500mg), and matching placebo, assessed over a 24 hour period.	between weeks 2-3 of treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	up to 8 weeks
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.	up to 8 weeks

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Verica Milivojevic, PhD, Yale University

Study record dates

Study Major Dates

• Study Start (Actual): March 12, 2019
• Primary Completion (Actual): May 8, 2023
• Study Completion (Actual): May 8, 2023

Study Registration Dates

• First Submitted: April 24, 2019
• First Submitted That Met QC Criteria: May 14, 2019
• First Posted (Actual): May 16, 2019

Study Record Updates

• Last Update Posted (Actual): July 3, 2024
• Last Update Submitted That Met QC Criteria: June 28, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Cocaine-Related Disorders
• Other Study ID Numbers: 1603017466; 1K01DA046561-01A1 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No