Alcohol Use Disorder
Conditions
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).
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.
Interventions
DRUGPregnenolone300
300mg
DRUGPregnenolone500
500mg
DRUGPlacebo
placebo
Sponsors
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-blinded
Intervention model description
Randomized Double-blind, placebo-controlled, parallel design
Eligibility
Sex/Gender
ALL
Age
18 Years to 68 Years
Healthy volunteers
No
Inclusion criteria
* Male or female individuals, ages 18 to 68. * 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, naltrexone or antabuse. * Any psychotic disorder or current Axis I psychiatric symptoms requiring specific attention. * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Drinking Days | up to 8 weeks | The mean percent drinking days as assessed by self report on daily smartphone monitoring and corroborated by the Substance Use Calendar over the 8 week period. |
| Percent Heavy Drinking Days | up to 8 weeks | The mean percent heavy drinking days as assessed by self report on daily smartphone monitoring and corroborated by the Substance Use Calendar over the 8 week period. |
| Number of Drinks Per Drinking Day | up to 8 weeks | Average number of drinks per drinking day as assessed by self report on daily smartphone monitoring and corroborated by the Substance Use Calendar over the 8 week period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Alcohol Craving | 8 week outcome period | Alcohol craving assessed using the weekly Obsessive Compulsive Drinking Scale (OCDS). This 14-item scale is a quick and reliable self-rating instrument that provides a total and two subscale scores that measure some cognitive aspects of alcohol craving. Obsessive subscale is the summation of items 1-6 with score range 0-24. Compulsive subscale is the summation of items 7-14 with score range 0-32. Total score range 0-40. Higher scores indicate more obsessions and compulsions with alcohol. |
| Weekly Negative Mood and Anxiety | assessed weekly, score at week 8 reported | The Hospital Anxiety and Depression Scale (HADS) will be used; it has 2 subscales (one for depression and one for anxiety) each with 7 items. It is a 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 with total score range from 0 to 21. Total scores are the sum of all items. Total scores are reported. Higher scores indicate higher levels of depression or anxiety. |
| Number of Participants With Treatment Emergent Adverse Events | up to 8 weeks | The Systematic Assessment of Treatment Emergent Events (SAFTEE) Questionnaire will be used to assess adverse events weekly during the trial. Data presented here is the number of participants that had any adverse events while on study. |
| Pregnenolone Levels | up to 8 weeks | Mean of blood levels of study drug assessed at 3 timepoints during the trial up to 8 weeks |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Patients Receiving 300mg PREG Patients randomly assigned to receive 300mg of pregnenolone (PREG) daily.
Pregnenolone300: 300mg | 29 |
| Patients Receiving 500mg PREG Patients randomly assigned to receive 500mg of pregnenolone (PREG) daily.
Pregnenolone500: 500mg | 30 |
| Placebo Patients randomly assigned to receive a placebo daily.
Placebo: placebo | 27 |
| Total | 86 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Dropped out before treatment | 1 | 0 | 4 |
| Overall Study | Lost to Follow-up | 2 | 5 | 8 |
Baseline characteristics
| Characteristic | Patients Receiving 300mg PREG | Total | Placebo | Patients Receiving 500mg PREG |
|---|---|---|---|---|
| Age, Continuous | 47.3 years STANDARD_DEVIATION 11.9 | 46.4 years STANDARD_DEVIATION 12.2 | 47.2 years STANDARD_DEVIATION 13.3 | 44.8 years STANDARD_DEVIATION 11.6 |
| Baseline Clinical Institute Withdrawal Assessment (CIWA) Score | 5.1 score on a scale STANDARD_DEVIATION 4.7 | 4.6 score on a scale STANDARD_DEVIATION 5.1 | 4.8 score on a scale STANDARD_DEVIATION 5.8 | 4 score on a scale STANDARD_DEVIATION 4.8 |
| Drinking Severity (AUDIT) | 17 score on a scale STANDARD_DEVIATION 6.7 | 18.8 score on a scale STANDARD_DEVIATION 7 | 20.3 score on a scale STANDARD_DEVIATION 6.7 | 19.2 score on a scale STANDARD_DEVIATION 7.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 6 Participants | 3 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 27 Participants | 80 Participants | 24 Participants | 29 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Lifetime Anxiety Disorder (including PTSD) | 9 Participants | 28 Participants | 10 Participants | 9 Participants |
| Lifetime Mood Disorder | 9 Participants | 24 Participants | 5 Participants | 10 Participants |
| Number of Participants Currently on Medications | 17 Participants | 46 Participants | 14 Participants | 15 Participants |
| Number of participants on depression medications | 4 Participants | 14 Participants | 5 Participants | 5 Participants |
| Number of regular smokers | 12 Participants | 34 Participants | 9 Participants | 13 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 27 Participants | 11 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 10 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) White | 17 Participants | 49 Participants | 12 Participants | 20 Participants |
| Region of Enrollment United States | 29 participants | 86 participants | 27 participants | 30 participants |
| Sex: Female, Male Female | 10 Participants | 31 Participants | 10 Participants | 11 Participants |
| Sex: Female, Male Male | 19 Participants | 55 Participants | 17 Participants | 19 Participants |
| Total number of medical conditions | 17 medical conditions | 44 medical conditions | 12 medical conditions | 15 medical conditions |
| World Health Organization (WHO) Severity High | 6 Participants | 18 Participants | 6 Participants | 6 Participants |
| World Health Organization (WHO) Severity Low | 10 Participants | 28 Participants | 10 Participants | 8 Participants |
| World Health Organization (WHO) Severity Moderate | 7 Participants | 21 Participants | 5 Participants | 9 Participants |
| World Health Organization (WHO) Severity Very High | 6 Participants | 19 Participants | 6 Participants | 7 Participants |
| Years of Alcohol Use | 21.9 years STANDARD_DEVIATION 14.9 | 19.7 years STANDARD_DEVIATION 12.7 | 20 years STANDARD_DEVIATION 13.5 | 17.3 years STANDARD_DEVIATION 9.2 |
| Years of Education | 14 years STANDARD_DEVIATION 2.3 | 14.4 years STANDARD_DEVIATION 2.6 | 14.6 years STANDARD_DEVIATION 2.6 | 14.6 years STANDARD_DEVIATION 2.6 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 29 | 0 / 30 | 0 / 27 |
| other Total, other adverse events | 10 / 29 | 9 / 30 | 7 / 27 |
| serious Total, serious adverse events | 0 / 29 | 0 / 30 | 1 / 27 |
Outcome results
Primary
Number of Drinks Per Drinking Day
Average number of drinks per drinking day as assessed by self report on daily smartphone monitoring and corroborated by the Substance Use Calendar over the 8 week period.
Time frame: up to 8 weeks
Population: Participants who were randomized and received treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients Receiving 300mg PREG | Number of Drinks Per Drinking Day | 1.7 drinks | Standard Deviation 0.3 |
| Patients Receiving 500mg PREG | Number of Drinks Per Drinking Day | 2.5 drinks | Standard Deviation 0.5 |
| Placebo | Number of Drinks Per Drinking Day | 2.3 drinks | Standard Deviation 0.4 |
p-value: 0.044Fisher Exact
Primary
Percent Drinking Days
The mean percent drinking days as assessed by self report on daily smartphone monitoring and corroborated by the Substance Use Calendar over the 8 week period.
Time frame: up to 8 weeks
Population: Participants who were randomized and received treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients Receiving 300mg PREG | Percent Drinking Days | 38.5 percentage of drinking days | Standard Deviation 5.1 |
| Patients Receiving 500mg PREG | Percent Drinking Days | 46.6 percentage of drinking days | Standard Deviation 5.7 |
| Placebo | Percent Drinking Days | 53 percentage of drinking days | Standard Deviation 6.2 |
p-value: 0.009Fisher Exact
Primary
Percent Heavy Drinking Days
The mean percent heavy drinking days as assessed by self report on daily smartphone monitoring and corroborated by the Substance Use Calendar over the 8 week period.
Time frame: up to 8 weeks
Population: Participants who were randomized and received treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients Receiving 300mg PREG | Percent Heavy Drinking Days | 15.2 percentage of heavy drinking days | Standard Deviation 3.6 |
| Patients Receiving 500mg PREG | Percent Heavy Drinking Days | 23.7 percentage of heavy drinking days | Standard Deviation 5.1 |
| Placebo | Percent Heavy Drinking Days | 22.9 percentage of heavy drinking days | Standard Deviation 5.6 |
p-value: 0.019Fisher Exact
Secondary
Alcohol Craving
Alcohol craving assessed using the weekly Obsessive Compulsive Drinking Scale (OCDS). This 14-item scale is a quick and reliable self-rating instrument that provides a total and two subscale scores that measure some cognitive aspects of alcohol craving. Obsessive subscale is the summation of items 1-6 with score range 0-24. Compulsive subscale is the summation of items 7-14 with score range 0-32. Total score range 0-40. Higher scores indicate more obsessions and compulsions with alcohol.
Time frame: 8 week outcome period
Population: Participants who were randomized and received treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Patients Receiving 300mg PREG | Alcohol Craving | OCDS: Compulsive | 9.8 score on a scale | Standard Deviation 0.3 |
| Patients Receiving 300mg PREG | Alcohol Craving | OCDS: Total | 13.8 score on a scale | Standard Deviation 0.5 |
| Patients Receiving 300mg PREG | Alcohol Craving | OCDS: Obsessive | 4 score on a scale | Standard Deviation 0.2 |
| Patients Receiving 500mg PREG | Alcohol Craving | OCDS: Obsessive | 5.8 score on a scale | Standard Deviation 0.3 |
| Patients Receiving 500mg PREG | Alcohol Craving | OCDS: Compulsive | 10.4 score on a scale | Standard Deviation 0.4 |
| Patients Receiving 500mg PREG | Alcohol Craving | OCDS: Total | 16.2 score on a scale | Standard Deviation 0.6 |
| Placebo | Alcohol Craving | OCDS: Total | 20.4 score on a scale | Standard Deviation 0.7 |
| Placebo | Alcohol Craving | OCDS: Compulsive | 13.5 score on a scale | Standard Deviation 0.4 |
| Placebo | Alcohol Craving | OCDS: Obsessive | 6.9 score on a scale | Standard Deviation 0.4 |
Comparison: OCDS: Totalp-value: <0.001Fisher Exact
Comparison: OCDS: Obsessivep-value: <0.001Fisher Exact
Comparison: OCDS: Compulsivep-value: 0.003Fisher Exact
Secondary
Number of Participants With Treatment Emergent Adverse Events
The Systematic Assessment of Treatment Emergent Events (SAFTEE) Questionnaire will be used to assess adverse events weekly during the trial. Data presented here is the number of participants that had any adverse events while on study.
Time frame: up to 8 weeks
Population: Participants who were randomized and received treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Patients Receiving 300mg PREG | Number of Participants With Treatment Emergent Adverse Events | 10 Participants |
| Patients Receiving 500mg PREG | Number of Participants With Treatment Emergent Adverse Events | 9 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events | 8 Participants |
Secondary
Pregnenolone Levels
Mean of blood levels of study drug assessed at 3 timepoints during the trial up to 8 weeks
Time frame: up to 8 weeks
Population: Participants who were randomized and received treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients Receiving 300mg PREG | Pregnenolone Levels | 5.46 ng/dL | Standard Deviation 0.79 |
| Patients Receiving 500mg PREG | Pregnenolone Levels | 6.21 ng/dL | Standard Deviation 0.66 |
| Placebo | Pregnenolone Levels | 2.42 ng/dL | Standard Deviation 0.4 |
p-value: <0.0001Fisher Exact
Secondary
Weekly Negative Mood and Anxiety
The Hospital Anxiety and Depression Scale (HADS) will be used; it has 2 subscales (one for depression and one for anxiety) each with 7 items. It is a 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 with total score range from 0 to 21. Total scores are the sum of all items. Total scores are reported. Higher scores indicate higher levels of depression or anxiety.
Time frame: assessed weekly, score at week 8 reported
Population: Participants who were randomized and received treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Patients Receiving 300mg PREG | Weekly Negative Mood and Anxiety | HADS-Depression | 4.53 score on a scale | Standard Deviation 0.26 |
| Patients Receiving 300mg PREG | Weekly Negative Mood and Anxiety | HADS-Anxiety | 5.36 score on a scale | Standard Deviation 0.24 |
| Patients Receiving 500mg PREG | Weekly Negative Mood and Anxiety | HADS-Depression | 4.85 score on a scale | Standard Deviation 0.24 |
| Patients Receiving 500mg PREG | Weekly Negative Mood and Anxiety | HADS-Anxiety | 6.49 score on a scale | Standard Deviation 0.27 |
| Placebo | Weekly Negative Mood and Anxiety | HADS-Anxiety | 7.31 score on a scale | Standard Deviation 0.32 |
| Placebo | Weekly Negative Mood and Anxiety | HADS-Depression | 6.55 score on a scale | Standard Deviation 0.35 |
Comparison: HADS-Depressionp-value: <0.001Fisher Exact
Comparison: HADS-Anxietyp-value: 0.089Fisher Exact