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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03872128
Recruitment Status : Recruiting
First Posted : March 13, 2019
Last Update Posted : March 13, 2019
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 alcohol use disorder (AUD).

Condition or disease Intervention/treatment Phase
Alcohol Use Disorder Drug: Pregnenolone Other: placebo Early Phase 1

Detailed Description:
The study aims to examine the effects of PREG on a) alcohol craving, mood and neuroendocrine reactivity to brief, guided imagery exposure to stress, drug cues and neutral situations in the laboratory and b) daily alcohol intake, craving, cognition and mood in men and women with AUD; and c) sex differences in all of these outcomes.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: random blind parallel
Masking: Single (Participant)
Masking Description: blinded
Primary Purpose: Treatment
Official Title: The Role of Neuroactive Steroids in Stress, Alcohol Craving and Alcohol Use in Alcohol Use Disorders
Actual Study Start Date : September 27, 2018
Estimated Primary Completion Date : June 30, 2023
Estimated Study Completion Date : June 30, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Alcohol

Arm Intervention/treatment
Active Comparator: patients receiving 300mg PREG
30 patients randomly assigned to receive 300mg of pregnenolone (PREG) daily.
Drug: Pregnenolone

Active Comparator: patients receiving 500mg PREG
30 patients randomly assigned to receive 500mg of pregnenolone (PREG) daily.
Drug: Pregnenolone

Placebo Comparator: placebo
30 patients randomly assigned to receive a placebo daily.
Other: placebo

Primary Outcome Measures :
  1. Reduce alcohol use [ Time Frame: 8 weeks ]
    Change compared to baseline in percent heavy drinking days and any drinking days as well as number of drinks per drinking day will be the main outcomes. These will be assessed by self report on the Substance Use Calendar, daily smartphone monitoring and corroborated by weekly urine toxicology and breathalyzer screening.

Secondary Outcome Measures :
  1. Alcohol craving reactivity in the laboratory [ Time Frame: in week 2 ]
    Alcohol 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. Alcohol craving will be assessed using a 10-point visual analog scale (VAS) in which 0="not at all" and 10="extremely high".

  2. Neuroendocrine/cortisol reactivity [ Time Frame: in week 2 ]
    Plasma will be collected at each laboratory session to assess cortisol response to stress, drug cue and neutral imagery exposure.

  3. Cardiovascular functioning in the laboratory. [ Time Frame: 2 weeks ]
    An Electrocardiograph (ECG) monitor will be placed during the laboratory sessions in week 2 to assess change in heart rate and blood pressures.

  4. Weekly Perceived Stress [ Time Frame: 8 weeks ]
    Perceived Stress Scale from 0-4 with 4 being highest score.

  5. Provoked negative emotion and anxiety [ Time Frame: in week 2 ]
    Differential Emotion Scale (DES). 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. Weekly alcohol craving [ Time Frame: weekly over the 8 week period ]
    Alcohol craving will be measured using the Alcohol Urge Questionnaire (AUQ), which is a brief 8-item self-report craving scale. Subjects are asked to rate on a Likert Scale ranging from 1-7 how strongly they disagree or agree with a statement regarding the urge for alcohol.

  7. Weekly Negative mood and anxiety [ Time Frame: 8 weeks ]
    The Hospital Anxiety and Depression Scale (HADS) will be used; it is a 7 item, brief measure of generalized symptoms of anxiety and fear. Respondents indicate how they currently feel and responses are rated on a 4-point Likert scale and range from 0 to 3.

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

  9. Adverse Events [ Time Frame: 8 weeks ]
    The Systematic Assessment of Treatment Emergent Events (SAFTEE) Questionnaire will be used to assess adverse events weekly during the trial.

  10. Alcohol withdrawal severity [ Time Frame: 8 weeks ]
    Alcohol withdrawal signs and symptoms will be measured weekly using the Clinical Institute Withdrawal Assessment (CIWA), which is a 13-item scale assessment. Items on this scale include objective measures (e.g., pulse), participants' responses to questions, such as orientation to time and space ("What day is this? Where are you? Who am I?"), and observations by the interviewer (evidence of tremor or paroxysmal sweats). Item responses range from 0 indicating no evidence of the symptom to 4 indicating highest severity of symptoms and possible total scores could range from 0 to 67.

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

Inclusion Criteria:

  • Male or female individuals, ages 18 to 60.
  • Subjects must meet current Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-V) criteria for alcohol use disorder; documented positive urine toxicology screen for alcohol 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/Phencyclidine (PCP), excluding alcohol and nicotine.
  • Any current use of opiates or past history of opiate use disorder (assessed via urine toxicology and self report).
  • Current use of any psychoactive drugs (urine toxicology), 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.
  • 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 identifier (NCT number): NCT03872128

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Contact: Rajita Sinha, PhD 203-737-5805
Contact: Julie Pinto, MS 203-737-5489

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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   
Principal Investigator: Rajita Sinha, PhD         
Sponsors and Collaborators
Yale University

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Responsible Party: Yale University Identifier: NCT03872128     History of Changes
Other Study ID Numbers: 1608018179
First Posted: March 13, 2019    Key Record Dates
Last Update Posted: March 13, 2019
Last Verified: March 2019

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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.: Yes
Additional relevant MeSH terms:
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Alcohol Drinking
Drinking Behavior
Alcohol-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Anti-Infective Agents, Local
Anti-Infective Agents
Central Nervous System Depressants
Physiological Effects of Drugs