Trial Outcomes & Findings for The Role of Neuroactive Steroids in Stress, Alcohol Craving and Alcohol Use in Alcohol Use Disorders (NCT NCT03872128)

NCT ID: NCT03872128

Last Updated: 2024-02-05

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 91 participants
• Primary outcome timeframe: up to 8 weeks
• Results posted on: 2024-02-05

Participant Flow

Participant milestones

Measure	Patients Receiving 300mg PREG Patients randomly assigned to receive 300mg of pregnenolone (PREG) daily. Pregnenolone300: 300mg	Patients Receiving 500mg PREG Patients randomly assigned to receive 500mg of pregnenolone (PREG) daily. Pregnenolone500: 500mg	Placebo Patients randomly assigned to receive a placebo daily. Placebo: placebo
Overall Study STARTED	30	30	31
Overall Study Began Treatment	29	30	27
Overall Study COMPLETED	27	25	19
Overall Study NOT COMPLETED	3	5	12

Reasons for withdrawal

Measure	Patients Receiving 300mg PREG Patients randomly assigned to receive 300mg of pregnenolone (PREG) daily. Pregnenolone300: 300mg	Patients Receiving 500mg PREG Patients randomly assigned to receive 500mg of pregnenolone (PREG) daily. Pregnenolone500: 500mg	Placebo Patients randomly assigned to receive a placebo daily. Placebo: placebo
Overall Study Dropped out before treatment	1	0	4
Overall Study Lost to Follow-up	2	5	8

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Patients Receiving 300mg PREG n=29 Participants Patients randomly assigned to receive 300mg of pregnenolone (PREG) daily. Pregnenolone300: 300mg	Patients Receiving 500mg PREG n=30 Participants Patients randomly assigned to receive 500mg of pregnenolone (PREG) daily. Pregnenolone500: 500mg	Placebo n=27 Participants Patients randomly assigned to receive a placebo daily. Placebo: placebo	Total n=86 Participants Total of all reporting groups
Age, Continuous	47.3 years STANDARD_DEVIATION 11.9 • n=5 Participants	44.8 years STANDARD_DEVIATION 11.6 • n=7 Participants	47.2 years STANDARD_DEVIATION 13.3 • n=5 Participants	46.4 years STANDARD_DEVIATION 12.2 • n=4 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	11 Participants n=7 Participants	10 Participants n=5 Participants	31 Participants n=4 Participants
Sex: Female, Male Male	19 Participants n=5 Participants	19 Participants n=7 Participants	17 Participants n=5 Participants	55 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	6 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	27 Participants n=5 Participants	29 Participants n=7 Participants	24 Participants n=5 Participants	80 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	8 Participants n=5 Participants	8 Participants n=7 Participants	11 Participants n=5 Participants	27 Participants n=4 Participants
Race (NIH/OMB) White	17 Participants n=5 Participants	20 Participants n=7 Participants	12 Participants n=5 Participants	49 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants	10 Participants n=4 Participants
Region of Enrollment United States	29 participants n=5 Participants	30 participants n=7 Participants	27 participants n=5 Participants	86 participants n=4 Participants
Years of Education	14 years STANDARD_DEVIATION 2.3 • n=5 Participants	14.6 years STANDARD_DEVIATION 2.6 • n=7 Participants	14.6 years STANDARD_DEVIATION 2.6 • n=5 Participants	14.4 years STANDARD_DEVIATION 2.6 • n=4 Participants
Number of regular smokers	12 Participants n=5 Participants	13 Participants n=7 Participants	9 Participants n=5 Participants	34 Participants n=4 Participants
Years of Alcohol Use	21.9 years STANDARD_DEVIATION 14.9 • n=5 Participants	17.3 years STANDARD_DEVIATION 9.2 • n=7 Participants	20 years STANDARD_DEVIATION 13.5 • n=5 Participants	19.7 years STANDARD_DEVIATION 12.7 • n=4 Participants
Drinking Severity (AUDIT)	17 score on a scale STANDARD_DEVIATION 6.7 • n=5 Participants	19.2 score on a scale STANDARD_DEVIATION 7.5 • n=7 Participants	20.3 score on a scale STANDARD_DEVIATION 6.7 • n=5 Participants	18.8 score on a scale STANDARD_DEVIATION 7 • n=4 Participants
World Health Organization (WHO) Severity Low	10 Participants n=5 Participants	8 Participants n=7 Participants	10 Participants n=5 Participants	28 Participants n=4 Participants
World Health Organization (WHO) Severity Moderate	7 Participants n=5 Participants	9 Participants n=7 Participants	5 Participants n=5 Participants	21 Participants n=4 Participants
World Health Organization (WHO) Severity High	6 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	18 Participants n=4 Participants
World Health Organization (WHO) Severity Very High	6 Participants n=5 Participants	7 Participants n=7 Participants	6 Participants n=5 Participants	19 Participants n=4 Participants
Baseline Clinical Institute Withdrawal Assessment (CIWA) Score	5.1 score on a scale STANDARD_DEVIATION 4.7 • n=5 Participants	4 score on a scale STANDARD_DEVIATION 4.8 • n=7 Participants	4.8 score on a scale STANDARD_DEVIATION 5.8 • n=5 Participants	4.6 score on a scale STANDARD_DEVIATION 5.1 • n=4 Participants
Lifetime Mood Disorder	9 Participants n=5 Participants	10 Participants n=7 Participants	5 Participants n=5 Participants	24 Participants n=4 Participants
Lifetime Anxiety Disorder (including PTSD)	9 Participants n=5 Participants	9 Participants n=7 Participants	10 Participants n=5 Participants	28 Participants n=4 Participants
Number of Participants Currently on Medications	17 Participants n=5 Participants	15 Participants n=7 Participants	14 Participants n=5 Participants	46 Participants n=4 Participants
Number of participants on depression medications	4 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants	14 Participants n=4 Participants
Total number of medical conditions	17 medical conditions n=5 Participants	15 medical conditions n=7 Participants	12 medical conditions n=5 Participants	44 medical conditions n=4 Participants

PRIMARY outcome

Timeframe: up to 8 weeks

Population: Participants who were randomized and received treatment.

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.

Outcome measures

Measure	Patients Receiving 300mg PREG n=29 Participants Patients randomly assigned to receive 300mg of pregnenolone (PREG) daily. Pregnenolone300: 300mg	Patients Receiving 500mg PREG n=30 Participants Patients randomly assigned to receive 500mg of pregnenolone (PREG) daily. Pregnenolone500: 500mg	Placebo n=27 Participants Patients randomly assigned to receive a placebo daily. Placebo: placebo
Percent Drinking Days	38.5 percentage of drinking days Standard Deviation 5.1	46.6 percentage of drinking days Standard Deviation 5.7	53 percentage of drinking days Standard Deviation 6.2

PRIMARY outcome

Timeframe: up to 8 weeks

Population: Participants who were randomized and received treatment.

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.

Outcome measures

Measure	Patients Receiving 300mg PREG n=29 Participants Patients randomly assigned to receive 300mg of pregnenolone (PREG) daily. Pregnenolone300: 300mg	Patients Receiving 500mg PREG n=30 Participants Patients randomly assigned to receive 500mg of pregnenolone (PREG) daily. Pregnenolone500: 500mg	Placebo n=27 Participants Patients randomly assigned to receive a placebo daily. Placebo: placebo
Percent Heavy Drinking Days	15.2 percentage of heavy drinking days Standard Deviation 3.6	23.7 percentage of heavy drinking days Standard Deviation 5.1	22.9 percentage of heavy drinking days Standard Deviation 5.6

PRIMARY outcome

Timeframe: up to 8 weeks

Population: Participants who were randomized and received treatment.

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.

Outcome measures

Measure	Patients Receiving 300mg PREG n=29 Participants Patients randomly assigned to receive 300mg of pregnenolone (PREG) daily. Pregnenolone300: 300mg	Patients Receiving 500mg PREG n=30 Participants Patients randomly assigned to receive 500mg of pregnenolone (PREG) daily. Pregnenolone500: 500mg	Placebo n=27 Participants Patients randomly assigned to receive a placebo daily. Placebo: placebo
Number of Drinks Per Drinking Day	1.7 drinks Standard Deviation 0.3	2.5 drinks Standard Deviation 0.5	2.3 drinks Standard Deviation 0.4

SECONDARY outcome

Timeframe: 8 week outcome period

Population: Participants who were randomized and received treatment.

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.

Outcome measures

Measure	Patients Receiving 300mg PREG n=29 Participants Patients randomly assigned to receive 300mg of pregnenolone (PREG) daily. Pregnenolone300: 300mg	Patients Receiving 500mg PREG n=30 Participants Patients randomly assigned to receive 500mg of pregnenolone (PREG) daily. Pregnenolone500: 500mg	Placebo n=27 Participants Patients randomly assigned to receive a placebo daily. Placebo: placebo
Alcohol Craving OCDS: Total	13.8 score on a scale Standard Deviation 0.5	16.2 score on a scale Standard Deviation 0.6	20.4 score on a scale Standard Deviation 0.7
Alcohol Craving OCDS: Obsessive	4 score on a scale Standard Deviation 0.2	5.8 score on a scale Standard Deviation 0.3	6.9 score on a scale Standard Deviation 0.4
Alcohol Craving OCDS: Compulsive	9.8 score on a scale Standard Deviation 0.3	10.4 score on a scale Standard Deviation 0.4	13.5 score on a scale Standard Deviation 0.4

SECONDARY outcome

Timeframe: up to 8 weeks

Population: Participants who were randomized and received treatment.

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.

Outcome measures

Measure	Patients Receiving 300mg PREG n=29 Participants Patients randomly assigned to receive 300mg of pregnenolone (PREG) daily. Pregnenolone300: 300mg	Patients Receiving 500mg PREG n=30 Participants Patients randomly assigned to receive 500mg of pregnenolone (PREG) daily. Pregnenolone500: 500mg	Placebo n=27 Participants Patients randomly assigned to receive a placebo daily. Placebo: placebo
Number of Participants With Treatment Emergent Adverse Events	10 Participants	9 Participants	8 Participants

SECONDARY outcome

Timeframe: up to 8 weeks

Population: Participants who were randomized and received treatment.

Mean of blood levels of study drug assessed at 3 timepoints during the trial up to 8 weeks

Outcome measures

Measure	Patients Receiving 300mg PREG n=29 Participants Patients randomly assigned to receive 300mg of pregnenolone (PREG) daily. Pregnenolone300: 300mg	Patients Receiving 500mg PREG n=30 Participants Patients randomly assigned to receive 500mg of pregnenolone (PREG) daily. Pregnenolone500: 500mg	Placebo n=27 Participants Patients randomly assigned to receive a placebo daily. Placebo: placebo
Pregnenolone Levels	5.46 ng/dL Standard Deviation 0.79	6.21 ng/dL Standard Deviation 0.66	2.42 ng/dL Standard Deviation 0.4

SECONDARY outcome

Timeframe: assessed weekly, score at week 8 reported

Population: Participants who were randomized and received treatment.

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.

Outcome measures

Measure	Patients Receiving 300mg PREG n=29 Participants Patients randomly assigned to receive 300mg of pregnenolone (PREG) daily. Pregnenolone300: 300mg	Patients Receiving 500mg PREG n=30 Participants Patients randomly assigned to receive 500mg of pregnenolone (PREG) daily. Pregnenolone500: 500mg	Placebo n=27 Participants Patients randomly assigned to receive a placebo daily. Placebo: placebo
Weekly Negative Mood and Anxiety HADS-Depression	4.53 score on a scale Standard Deviation 0.26	4.85 score on a scale Standard Deviation 0.24	6.55 score on a scale Standard Deviation 0.35
Weekly Negative Mood and Anxiety HADS-Anxiety	5.36 score on a scale Standard Deviation 0.24	6.49 score on a scale Standard Deviation 0.27	7.31 score on a scale Standard Deviation 0.32

Adverse Events

Patients Receiving 300mg PREG

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Patients Receiving 500mg PREG

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Measure	Patients Receiving 300mg PREG n=29 participants at risk Patients randomly assigned to receive 300mg of pregnenolone (PREG) daily. Pregnenolone300: 300mg	Patients Receiving 500mg PREG n=30 participants at risk Patients randomly assigned to receive 500mg of pregnenolone (PREG) daily. Pregnenolone500: 500mg	Placebo n=27 participants at risk Patients randomly assigned to receive a placebo daily. Placebo: placebo
General disorders General disorders and administration site conditions - Other, specify	0.00% 0/29 • up to 8 weeks	0.00% 0/30 • up to 8 weeks	3.7% 1/27 • up to 8 weeks

Other adverse events

Measure	Patients Receiving 300mg PREG n=29 participants at risk Patients randomly assigned to receive 300mg of pregnenolone (PREG) daily. Pregnenolone300: 300mg	Patients Receiving 500mg PREG n=30 participants at risk Patients randomly assigned to receive 500mg of pregnenolone (PREG) daily. Pregnenolone500: 500mg	Placebo n=27 participants at risk Patients randomly assigned to receive a placebo daily. Placebo: placebo
Nervous system disorders Headache	10.3% 3/29 • up to 8 weeks	6.7% 2/30 • up to 8 weeks	7.4% 2/27 • up to 8 weeks
Musculoskeletal and connective tissue disorders Back pain	6.9% 2/29 • up to 8 weeks	3.3% 1/30 • up to 8 weeks	3.7% 1/27 • up to 8 weeks
Injury, poisoning and procedural complications Injury, poisoning and procedural complications - Other, specif	10.3% 3/29 • up to 8 weeks	13.3% 4/30 • up to 8 weeks	0.00% 0/27 • up to 8 weeks
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	6.9% 2/29 • up to 8 weeks	3.3% 1/30 • up to 8 weeks	7.4% 2/27 • up to 8 weeks
Infections and infestations Infections and infestations - Other, specify	10.3% 3/29 • up to 8 weeks	3.3% 1/30 • up to 8 weeks	3.7% 1/27 • up to 8 weeks
Immune system disorders Immune system disorders - Other, specify	3.4% 1/29 • up to 8 weeks	3.3% 1/30 • up to 8 weeks	0.00% 0/27 • up to 8 weeks
Reproductive system and breast disorders Reproductive system and breast disorders - Other, specify	3.4% 1/29 • up to 8 weeks	6.7% 2/30 • up to 8 weeks	0.00% 0/27 • up to 8 weeks
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify	0.00% 0/29 • up to 8 weeks	3.3% 1/30 • up to 8 weeks	0.00% 0/27 • up to 8 weeks
Nervous system disorders Nervous system disorders - Other, specify	3.4% 1/29 • up to 8 weeks	0.00% 0/30 • up to 8 weeks	0.00% 0/27 • up to 8 weeks
General disorders General disorders and administration site conditions - Other, specify	0.00% 0/29 • up to 8 weeks	3.3% 1/30 • up to 8 weeks	3.7% 1/27 • up to 8 weeks

Additional Information

Nia Fogelman

Yale University

Phone: (917)861-9865

Email: nia.fogelman@yale.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place