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

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ClinicalTrials.gov Identifier: NCT03953612
Recruitment Status : Recruiting
First Posted : May 16, 2019
Last Update Posted : May 16, 2019
Sponsor:
Information provided by (Responsible Party):
Yale University

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).

Condition or disease Intervention/treatment Phase
Cocaine-Related Disorders Drug: PREG 300/500 mg Drug: Placebos Early Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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: Single (Participant)
Primary Purpose: Treatment
Official Title: The Role of Neuroactive Steroids in Stress, Drug Craving and Drug Use in Cocaine Use Disorders
Actual Study Start Date : March 12, 2019
Estimated Primary Completion Date : February 2024
Estimated Study Completion Date : February 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: patients receiving PREG
Eligible participants will then be admitted to the Clinical Neuroscience Research Unit (CNRU) at the Connecticut Mental Health Center (CMHC) and randomly assigned to 2 doses of PREG (300/500 mg/day)over 8 weeks.
Drug: PREG 300/500 mg
2 doses of PREG (300/500 mg/day)

Placebo Comparator: patients receiving placebo
Eligible participants will then be admitted to the Clinical Neuroscience Research Unit (CNRU) at the CMHC and randomly assigned to a placebo (PLA) treatment (N=20/group) over 8 weeks.
Drug: Placebos
placebo




Primary Outcome Measures :
  1. Craving reactivity in the laboratory [ Time Frame: in week 2 of treatment ]
    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".

  2. Plasma cortisol levels as a measure of stress response in the laboratory [ Time Frame: in week 2 of treatment ]
    Plasma will be collected at each laboratory session to assess cortisol response to stress, drug cue and neutral imagery exposure.

  3. Blood pressure responses in the laboratory [ Time Frame: in week 2 of treatment ]
    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.

  4. Heart rate beats per minutes responses in the laboratory [ Time Frame: in week 2 of treatment ]
    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.

  5. Provoked negative emotion and anxiety [ Time Frame: in week 2 of treatment ]
    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.

  6. Provoked cognitive flexibility [ Time Frame: in week 2 of treatment ]
    Stroop Color Word Test during stress, drug cue and neutral provocation

  7. Area under the curve (Pharmacokinetic Profile ) [ Time Frame: in week 2 of treatment ]
    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.

  8. Maximum Plasma Concentration (Cmax); Pharmacokinetic Profile [ Time Frame: in week 2 of treatment ]
    The maximum (peak) plasma concentration achieved after two doses of PREG (300mg;500mg; bid) will be calculated.

  9. Plasma Half-Life (t1/2) of Pregnenolone [ Time Frame: in week 2 of treatment ]
    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.

  10. Change from baseline Adverse Events [ Time Frame: at week 8 ]
    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 :
  1. Cocaine use as secondary clinical outcome using urine toxicology. [ Time Frame: weekly during 8 weeks ]
    Percent of positive urine tests during the 8 week trial will be assessed by a weekly urine toxicology screening.

  2. Cocaine use amount as secondary clinical outcome using Timeline Followback Substance Use Calendar. [ Time Frame: weekly during 8 weeks ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03953612


Contacts
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Contact: Verica Milivojevic, PhD 203-737-5201 verica.milivojevic@yale.edu
Contact: Julie Pinto, MS 203-737-5489 julie.pinto@yale.edu

Locations
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United States, Connecticut
Yale Stress Center Recruiting
New Haven, Connecticut, United States, 06519
Contact: Rachel L Hart, MS    203-737-4791    rachel.hart@yale.edu   
Principal Investigator: Verica Milivojevic, PhD         
Sponsors and Collaborators
Yale University
Investigators
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Principal Investigator: Verica Milivojevic, PhD Yale University

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Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT03953612     History of Changes
Other Study ID Numbers: 1603017466
First Posted: May 16, 2019    Key Record Dates
Last Update Posted: May 16, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Disease
Cocaine-Related Disorders
Pathologic Processes
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Cocaine
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents
Vasoconstrictor Agents
Dopamine Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Dopamine Agents
Neurotransmitter Agents