Trial Outcomes & Findings for A Neurosteroid Intervention for Menopausal and Perimenopausal Depression (NCT NCT03505905)
NCT ID: NCT03505905
Last Updated: 2026-01-22
Results Overview
The Montgomery-Asberg Depression Rating Scale (MADRS; primary outcome) is an observer-rated 10-item measure of depressive symptomatology designed for use in clinical trials. Each item is rated from 0-6 in order of increasing severity based upon the assessment of symptoms within the past 7 days. The range of total scores is 0-60, with higher score indicative of more severe depressive symptoms.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
73 participants
Primary outcome timeframe
Phase 1 timeframe is Baseline to Week 8; Phase 2 timeframe is Week 8 to Week 16
Results posted on
2026-01-22
Participant Flow
Participant milestones
| Measure |
Group 1: Pregnenolone - Pregnenolone
Phase 1 - Pregnenolone. Phase 2 - Pregnenolone.
Group 1 includes participants who received pregnenolone in Phase 1 and in Phase 2. Group 1 also includes participants who received pregnenolone in Phase 1 but did not complete Phase 1 and thus did not start Phase 2. These participants were grouped here because, per Sequential Parallel Comparison Design (SPCD), participants who are randomized to receive pregnenolone in Phase 1 continue to receive pregnenolone in Phase 2.
|
Group 2: Placebo - Pregnenolone
Phase 1 - Placebo. Phase 2 - Pregnenolone.
Group 2 includes participants who received placebo in Phase 1, were non-responders, and were then re-randomized to receive pregnenolone in Phase 2. Per Sequential Parallel Comparison Design (SPCD), participants will be randomized to receive placebo or pregnenolone in a 2:1 ratio in Phase 1. Then, placebo non-responders in Phase 1 will be re-randomized in Phase 2 to receive placebo or pregnenolone in a 1:1 ratio.
|
Group 3: Placebo - Placebo
Phase 1 - Placebo. Phase 2 - Placebo.
Group 3 includes participants who received placebo in Phase 1, were non-responders, and were then re-randomized to receive placebo in Phase 2. Per Sequential Parallel Comparison Design (SPCD), participants will be randomized to receive placebo or pregnenolone in a 2:1 ratio in Phase 1. Then, placebo non-responders in Phase 1 will be re-randomized in Phase 2 to receive placebo or pregnenolone in a 1:1 ratio.
|
Group 4: Placebo - No Phase 2
Phase 1 - Placebo. Phase 2 - Drop Outs \& Placebo Responders.
Group 4 includes participants who received placebo and dropped out in Phase 1 and did not proceed to Phase 2. Group 4 also includes all placebo responders regardless of whether they proceeded to Phase 2 since all placebo responders continue receiving placebo in Phase 2.
|
|---|---|---|---|---|
|
Phase 1
STARTED
|
26
|
9
|
7
|
31
|
|
Phase 1
COMPLETED
|
16
|
9
|
7
|
17
|
|
Phase 1
NOT COMPLETED
|
10
|
0
|
0
|
14
|
|
Phase 2
STARTED
|
16
|
9
|
7
|
17
|
|
Phase 2
COMPLETED
|
14
|
8
|
6
|
15
|
|
Phase 2
NOT COMPLETED
|
2
|
1
|
1
|
2
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Neurosteroid Intervention for Menopausal and Perimenopausal Depression
Baseline characteristics by cohort
| Measure |
Group 1: Pregnenolone - Pregnenolone
n=26 Participants
Phase 1 - Pregnenolone. Phase 2 - Pregnenolone.
Group 1 includes participants who received pregnenolone in Phase 1 and in Phase 2. Group 1 also includes participants who received pregnenolone in Phase 1 but did not complete Phase 1 and thus did not start Phase 2. These participants were grouped here because, per Sequential Parallel Comparison Design (SPCD), participants who are randomized to receive pregnenolone in Phase 1 continue to receive pregnenolone in Phase 2.
|
Group 2: Placebo - Pregnenolone
n=9 Participants
Phase 1 - Placebo. Phase 2 - Pregnenolone.
Group 2 includes participants who received placebo in Phase 1, were non-responders, and were then re-randomized to receive pregnenolone in Phase 2. Per Sequential Parallel Comparison Design (SPCD), participants will be randomized to receive placebo or pregnenolone in a 2:1 ratio in Phase 1. Then, placebo non-responders in Phase 1 will be re-randomized in Phase 2 to receive placebo or pregnenolone in a 1:1 ratio.
|
Group 3: Placebo - Placebo
n=7 Participants
Phase 1 - Placebo. Phase 2 - Placebo.
Group 3 includes participants who received placebo in Phase 1, were non-responders, and were then re-randomized to receive placebo in Phase 2. Per Sequential Parallel Comparison Design (SPCD), participants will be randomized to receive placebo or pregnenolone in a 2:1 ratio in Phase 1. Then, placebo non-responders in Phase 1 will be re-randomized in Phase 2 to receive placebo or pregnenolone in a 1:1 ratio.
|
Group 4: Placebo - No Phase 2
n=31 Participants
Phase 1 - Placebo. Phase 2 - Drop Outs \& Placebo Responders.
Group 4 includes participants who received placebo and dropped out in Phase 1 and did not proceed to Phase 2. Group 4 also includes all placebo responders regardless of whether they proceeded to Phase 2 since all placebo responders continue receiving placebo in Phase 2.
|
Total
n=73 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=270 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=9 Participants
|
0 Participants
n=220 Participants
|
0 Participants
n=3 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
25 Participants
n=270 Participants
|
8 Participants
n=4 Participants
|
7 Participants
n=9 Participants
|
31 Participants
n=220 Participants
|
71 Participants
n=3 Participants
|
|
Age, Categorical
>=65 years
|
1 Participants
n=270 Participants
|
1 Participants
n=4 Participants
|
0 Participants
n=9 Participants
|
0 Participants
n=220 Participants
|
2 Participants
n=3 Participants
|
|
Age, Continuous
|
51.27 Years
STANDARD_DEVIATION 6.87 • n=270 Participants
|
52.78 Years
STANDARD_DEVIATION 5.47 • n=4 Participants
|
51.29 Years
STANDARD_DEVIATION 6.32 • n=9 Participants
|
50.42 Years
STANDARD_DEVIATION 5.10 • n=220 Participants
|
51.09 Years
STANDARD_DEVIATION 5.87 • n=3 Participants
|
|
Sex: Female, Male
Female
|
26 Participants
n=270 Participants
|
9 Participants
n=4 Participants
|
7 Participants
n=9 Participants
|
31 Participants
n=220 Participants
|
73 Participants
n=3 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=270 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=9 Participants
|
0 Participants
n=220 Participants
|
0 Participants
n=3 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=270 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=9 Participants
|
0 Participants
n=220 Participants
|
0 Participants
n=3 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=270 Participants
|
2 Participants
n=4 Participants
|
1 Participants
n=9 Participants
|
3 Participants
n=220 Participants
|
6 Participants
n=3 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=270 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=9 Participants
|
1 Participants
n=220 Participants
|
1 Participants
n=3 Participants
|
|
Race (NIH/OMB)
Black or African American
|
10 Participants
n=270 Participants
|
1 Participants
n=4 Participants
|
2 Participants
n=9 Participants
|
6 Participants
n=220 Participants
|
19 Participants
n=3 Participants
|
|
Race (NIH/OMB)
White
|
15 Participants
n=270 Participants
|
6 Participants
n=4 Participants
|
4 Participants
n=9 Participants
|
18 Participants
n=220 Participants
|
43 Participants
n=3 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=270 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=9 Participants
|
2 Participants
n=220 Participants
|
3 Participants
n=3 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=270 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=9 Participants
|
1 Participants
n=220 Participants
|
1 Participants
n=3 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=270 Participants
|
1 Participants
n=4 Participants
|
0 Participants
n=9 Participants
|
7 Participants
n=220 Participants
|
11 Participants
n=3 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
23 Participants
n=270 Participants
|
8 Participants
n=4 Participants
|
7 Participants
n=9 Participants
|
24 Participants
n=220 Participants
|
62 Participants
n=3 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=270 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=9 Participants
|
0 Participants
n=220 Participants
|
0 Participants
n=3 Participants
|
PRIMARY outcome
Timeframe: Phase 1 timeframe is Baseline to Week 8; Phase 2 timeframe is Week 8 to Week 16Population: Due to the methods used in Sequential Parallel Comparison Design (SPCD), Phase 2 analysis only includes participants who were placebo non-responders in Phase 1. The total number of participants who received pregnenolone in Phase 1 was 26 and the total number of participants who received placebo in Phase 1 was 47. Those who received pregnenolone in Phase 1 continued to receive Pregnenolone in Phase 2. Placebo responders in Phase 1 continued to receive placebo in Phase 2.
The Montgomery-Asberg Depression Rating Scale (MADRS; primary outcome) is an observer-rated 10-item measure of depressive symptomatology designed for use in clinical trials. Each item is rated from 0-6 in order of increasing severity based upon the assessment of symptoms within the past 7 days. The range of total scores is 0-60, with higher score indicative of more severe depressive symptoms.
Outcome measures
| Measure |
Pregnenolone
n=26 Participants
Participants randomized to receive pregnenolone in Phase 1 continued to receive pregnenolone in Phase 2. The titration schedule was as follows: 50mg BID for 7 days at Baseline, 150mg BID for 7 days at Week 1, 250mg BID for 14 days at Week 2, and 250mg BID for 28 days at Week 4. Participants continued 250mg BID throughout Phase 2. At Week 16, participants titrated down at 150mg BID for 4 days and then 50mg BID for 4 days before discontinuing.
|
Placebo
n=47 Participants
Participants received placebo at the same frequency as those who received pregnenolone. Placebo responders in Phase 1 continued to received placebo in Phase 2. Placebo non-responders in Phase 1 were rerandomized to receive either placebo or pregnenolone in Phase 2.
|
|---|---|---|
|
Montgomery-Asberg Depression Rating Scale (MADRS)
Phase 1 - Baseline
|
26.2 units on a scale
Standard Deviation 5.0
|
27.0 units on a scale
Standard Deviation 4.5
|
|
Montgomery-Asberg Depression Rating Scale (MADRS)
Phase 1 - Week 8
|
15.7 units on a scale
Standard Deviation 7.2
|
15.2 units on a scale
Standard Deviation 8.7
|
|
Montgomery-Asberg Depression Rating Scale (MADRS)
Phase 1 - Change in Score
|
-11.8 units on a scale
Standard Deviation 8.3
|
-11.9 units on a scale
Standard Deviation 8.6
|
|
Montgomery-Asberg Depression Rating Scale (MADRS)
Phase 2 - Week 8
|
22.4 units on a scale
Standard Deviation 7.4
|
22.1 units on a scale
Standard Deviation 5.6
|
|
Montgomery-Asberg Depression Rating Scale (MADRS)
Phase 2 - Week 16
|
14.4 units on a scale
Standard Deviation 8.9
|
19.3 units on a scale
Standard Deviation 5.6
|
|
Montgomery-Asberg Depression Rating Scale (MADRS)
Phase 2 - Change in Score
|
-8.8 units on a scale
Standard Deviation 13.1
|
-3.5 units on a scale
Standard Deviation 6.0
|
SECONDARY outcome
Timeframe: Phase 1 timeframe is Baseline to Week 8; Phase 2 timeframe is Week 8 to Week 16Population: Due to the methods used in Sequential Parallel Comparison Design (SPCD), Phase 2 analysis only includes participants who were placebo non-responders in Phase 1. The total number of participants who received pregnenolone in Phase 1 was 26 and the total number of participants who received placebo in Phase 1 was 47. Those who received pregnenolone in Phase 1 continued to receive Pregnenolone in Phase 2. Placebo responders in Phase 1 continued to receive placebo in Phase 2.
The Hamilton Anxiety Rating Scale (HRSA) is a 14-item observer-rated scale that assesses the degree and pathology associated with anxiety such as anxious mood, tension, fear, and insomnia. Items are scored 0 (absent) through 4 (very severe) with the total score ranging from 0 to 56. Higher scores indicate a greater degree of anxiety symptoms.
Outcome measures
| Measure |
Pregnenolone
n=26 Participants
Participants randomized to receive pregnenolone in Phase 1 continued to receive pregnenolone in Phase 2. The titration schedule was as follows: 50mg BID for 7 days at Baseline, 150mg BID for 7 days at Week 1, 250mg BID for 14 days at Week 2, and 250mg BID for 28 days at Week 4. Participants continued 250mg BID throughout Phase 2. At Week 16, participants titrated down at 150mg BID for 4 days and then 50mg BID for 4 days before discontinuing.
|
Placebo
n=47 Participants
Participants received placebo at the same frequency as those who received pregnenolone. Placebo responders in Phase 1 continued to received placebo in Phase 2. Placebo non-responders in Phase 1 were rerandomized to receive either placebo or pregnenolone in Phase 2.
|
|---|---|---|
|
Hamilton Anxiety Rating Scale (HRSA)
Phase 1 - Week 8
|
14.5 units on a scale
Standard Deviation 5.6
|
12.9 units on a scale
Standard Deviation 5.3
|
|
Hamilton Anxiety Rating Scale (HRSA)
Phase 2 - Week 16
|
13.3 units on a scale
Standard Deviation 6.4
|
18.0 units on a scale
Standard Deviation 4.9
|
|
Hamilton Anxiety Rating Scale (HRSA)
Phase 1 - Baseline
|
19.4 units on a scale
Standard Deviation 5.1
|
19.2 units on a scale
Standard Deviation 5.5
|
|
Hamilton Anxiety Rating Scale (HRSA)
Phase 1 - Change in Score
|
-5.2 units on a scale
Standard Deviation 6.9
|
-5.5 units on a scale
Standard Deviation 5.3
|
|
Hamilton Anxiety Rating Scale (HRSA)
Phase 2 - Week 8
|
15.0 units on a scale
Standard Deviation 3.9
|
16.3 units on a scale
Standard Deviation 6.2
|
|
Hamilton Anxiety Rating Scale (HRSA)
Phase 2 - Change in Score
|
-2.3 units on a scale
Standard Deviation 4.5
|
0.8 units on a scale
Standard Deviation 4.8
|
SECONDARY outcome
Timeframe: Phase 1 timeframe is Baseline to Week 8; Phase 2 timeframe is Week 8 to Week 16Population: Due to the methods used in Sequential Parallel Comparison Design (SPCD), Phase 2 analysis only includes participants who were placebo non-responders in Phase 1. The total number of participants who received pregnenolone in Phase 1 was 26 and the total number of participants who received placebo in Phase 1 was 47. Those who received pregnenolone in Phase 1 continued to receive Pregnenolone in Phase 2. Placebo responders in Phase 1 continued to receive placebo in Phase 2.
The Pittsburgh Sleep Quality Index (PSQI) is a 9-item self-report scale used to assess sleep quality and disturbances during the past week. Total scores range from 0 to 21 with higher scores indicating poorer sleep quality. Total scores are calculated by adding together the scores of the 7 components (e.g., duration of sleep, sleep disturbance, sleep latency) that comprise the PSQI.
Outcome measures
| Measure |
Pregnenolone
n=26 Participants
Participants randomized to receive pregnenolone in Phase 1 continued to receive pregnenolone in Phase 2. The titration schedule was as follows: 50mg BID for 7 days at Baseline, 150mg BID for 7 days at Week 1, 250mg BID for 14 days at Week 2, and 250mg BID for 28 days at Week 4. Participants continued 250mg BID throughout Phase 2. At Week 16, participants titrated down at 150mg BID for 4 days and then 50mg BID for 4 days before discontinuing.
|
Placebo
n=47 Participants
Participants received placebo at the same frequency as those who received pregnenolone. Placebo responders in Phase 1 continued to received placebo in Phase 2. Placebo non-responders in Phase 1 were rerandomized to receive either placebo or pregnenolone in Phase 2.
|
|---|---|---|
|
Pittsburgh Sleep Quality Index (PSQI)
Phase 2 - Change in Score
|
-4.1 units on a scale
Standard Deviation 3.9
|
-0.5 units on a scale
Standard Deviation 2.9
|
|
Pittsburgh Sleep Quality Index (PSQI)
Phase 1 - Baseline
|
7.5 units on a scale
Standard Deviation 5.7
|
8.1 units on a scale
Standard Deviation 4.0
|
|
Pittsburgh Sleep Quality Index (PSQI)
Phase 1 - Week 8
|
5.8 units on a scale
Standard Deviation 4.9
|
6.2 units on a scale
Standard Deviation 4.4
|
|
Pittsburgh Sleep Quality Index (PSQI)
Phase 1 - Change in Score
|
-2.9 units on a scale
Standard Deviation 4.5
|
-2.5 units on a scale
Standard Deviation 3.9
|
|
Pittsburgh Sleep Quality Index (PSQI)
Phase 2 - Week 8
|
7.1 units on a scale
Standard Deviation 4.6
|
7.1 units on a scale
Standard Deviation 6.0
|
|
Pittsburgh Sleep Quality Index (PSQI)
Phase 2 - Week 16
|
3.4 units on a scale
Standard Deviation 1.6
|
5.5 units on a scale
Standard Deviation 4.7
|
SECONDARY outcome
Timeframe: Phase 1 timeframe is Baseline to Week 8; Phase 2 timeframe is Week 8 to Week 16Population: Due to the methods used in Sequential Parallel Comparison Design (SPCD), Phase 2 analysis only includes participants who were placebo non-responders in Phase 1. The total number of participants who received pregnenolone in Phase 1 was 26 and the total number of participants who received placebo in Phase 1 was 47. Those who received pregnenolone in Phase 1 continued to receive Pregnenolone in Phase 2. Placebo responders in Phase 1 continued to receive placebo in Phase 2.
The Menopause Specific Quality of Life (MEN-QOL) is a 29-item measure used to assess the presence and bother associated with 29-different menopausal symptoms. Items are scored 0 (not bothered at all) to 6 (extremely bothered) with total scores ranging from 0 to 174. Higher total scores indicate worse menopausal symptoms.
Outcome measures
| Measure |
Pregnenolone
n=26 Participants
Participants randomized to receive pregnenolone in Phase 1 continued to receive pregnenolone in Phase 2. The titration schedule was as follows: 50mg BID for 7 days at Baseline, 150mg BID for 7 days at Week 1, 250mg BID for 14 days at Week 2, and 250mg BID for 28 days at Week 4. Participants continued 250mg BID throughout Phase 2. At Week 16, participants titrated down at 150mg BID for 4 days and then 50mg BID for 4 days before discontinuing.
|
Placebo
n=47 Participants
Participants received placebo at the same frequency as those who received pregnenolone. Placebo responders in Phase 1 continued to received placebo in Phase 2. Placebo non-responders in Phase 1 were rerandomized to receive either placebo or pregnenolone in Phase 2.
|
|---|---|---|
|
Menopause Specific Quality of Life (MEN-QOL)
Phase 2 - Change in Score
|
-16.9 units on a scale
Standard Deviation 25.0
|
-8.0 units on a scale
Standard Deviation 24.9
|
|
Menopause Specific Quality of Life (MEN-QOL)
Phase 1 - Baseline
|
128.5 units on a scale
Standard Deviation 32.1
|
141.0 units on a scale
Standard Deviation 33.2
|
|
Menopause Specific Quality of Life (MEN-QOL)
Phase 1 - Week 8
|
83.3 units on a scale
Standard Deviation 32.8
|
95.3 units on a scale
Standard Deviation 35.4
|
|
Menopause Specific Quality of Life (MEN-QOL)
Phase 1 - Change in Score
|
-61.4 units on a scale
Standard Deviation 36.5
|
-50.3 units on a scale
Standard Deviation 30.3
|
|
Menopause Specific Quality of Life (MEN-QOL)
Phase 2 - Week 8
|
93.8 units on a scale
Standard Deviation 35.3
|
104.1 units on a scale
Standard Deviation 44.9
|
|
Menopause Specific Quality of Life (MEN-QOL)
Phase 2 - Week 16
|
78.0 units on a scale
Standard Deviation 34.2
|
105.8 units on a scale
Standard Deviation 41.0
|
SECONDARY outcome
Timeframe: Phase 1 timeframe is Baseline to Week 8; Phase 2 timeframe is Week 8 to Week 16Population: Due to the methods used in Sequential Parallel Comparison Design (SPCD), Phase 2 analysis only includes participants who were placebo non-responders in Phase 1. The total number of participants who received pregnenolone in Phase 1 was 26 and the total number of participants who received placebo in Phase 1 was 47. Those who received pregnenolone in Phase 1 continued to receive Pregnenolone in Phase 2. Placebo responders in Phase 1 continued to receive placebo in Phase 2.
The Greene Climacteric Scale (GCS) is a 21-item menopause symptom checklist providing an objective measure of mood disturbance, hot flushes, night sweats, and vaginal dryness. Items are scored from 0 (not at all) to 3 (extremely) with total scores ranging from 0 to 63. Higher total scores indicate worse menopause symptoms. Total scores are calculated by adding together the scores of the 3 subscales (e.g., psychological, vasomotor, physical) that comprise the GCS.
Outcome measures
| Measure |
Pregnenolone
n=26 Participants
Participants randomized to receive pregnenolone in Phase 1 continued to receive pregnenolone in Phase 2. The titration schedule was as follows: 50mg BID for 7 days at Baseline, 150mg BID for 7 days at Week 1, 250mg BID for 14 days at Week 2, and 250mg BID for 28 days at Week 4. Participants continued 250mg BID throughout Phase 2. At Week 16, participants titrated down at 150mg BID for 4 days and then 50mg BID for 4 days before discontinuing.
|
Placebo
n=47 Participants
Participants received placebo at the same frequency as those who received pregnenolone. Placebo responders in Phase 1 continued to received placebo in Phase 2. Placebo non-responders in Phase 1 were rerandomized to receive either placebo or pregnenolone in Phase 2.
|
|---|---|---|
|
Greene Climacteric Scale (GCS)
Phase 1 - Week 8
|
27.5 units on a scale
Standard Deviation 10.2
|
31.4 units on a scale
Standard Deviation 9.6
|
|
Greene Climacteric Scale (GCS)
Phase 1 - End of Phase
|
14.5 units on a scale
Standard Deviation 8.0
|
13.7 units on a scale
Standard Deviation 8.3
|
|
Greene Climacteric Scale (GCS)
Phase 1 - Change in Score
|
-16.8 units on a scale
Standard Deviation 8.3
|
-16.7 units on a scale
Standard Deviation 7.8
|
|
Greene Climacteric Scale (GCS)
Phase 2 - Week 8
|
15.9 units on a scale
Standard Deviation 7.5
|
20.8 units on a scale
Standard Deviation 10.2
|
|
Greene Climacteric Scale (GCS)
Phase 2 - Week 16
|
12.9 units on a scale
Standard Deviation 9.0
|
20.8 units on a scale
Standard Deviation 7.7
|
|
Greene Climacteric Scale (GCS)
Phase 2 - Change in Score
|
-2.9 units on a scale
Standard Deviation 6.9
|
-2.0 units on a scale
Standard Deviation 5.6
|
SECONDARY outcome
Timeframe: Phase 1 timeframe is Baseline to Week 8; Phase 2 timeframe is Week 8 to Week 16Population: Due to the methods used in Sequential Parallel Comparison Design (SPCD), Phase 2 analysis only includes participants who were placebo non-responders in Phase 1. The total number of participants who received pregnenolone in Phase 1 was 26 and the total number of participants who received placebo in Phase 1 was 47. Those who received pregnenolone in Phase 1 continued to receive Pregnenolone in Phase 2. Placebo responders in Phase 1 continued to receive placebo in Phase 2.
The Rey Auditory Verbal Learning Test (RAVLT) is an auditory assessment of verbal learning and memory, in which the participant is asked to recall a list of words first immediately following presentation (immediate recall) and later following a set period of time (delayed recall). Participant age, years of education, and sex are used to calculate t-scores. T-scores represent how an individual score compares to the mean / average score of that participant's demographic group. Higher t-scores indicate a greater recall of the list of words compared to the average score.
Outcome measures
| Measure |
Pregnenolone
n=26 Participants
Participants randomized to receive pregnenolone in Phase 1 continued to receive pregnenolone in Phase 2. The titration schedule was as follows: 50mg BID for 7 days at Baseline, 150mg BID for 7 days at Week 1, 250mg BID for 14 days at Week 2, and 250mg BID for 28 days at Week 4. Participants continued 250mg BID throughout Phase 2. At Week 16, participants titrated down at 150mg BID for 4 days and then 50mg BID for 4 days before discontinuing.
|
Placebo
n=47 Participants
Participants received placebo at the same frequency as those who received pregnenolone. Placebo responders in Phase 1 continued to received placebo in Phase 2. Placebo non-responders in Phase 1 were rerandomized to receive either placebo or pregnenolone in Phase 2.
|
|---|---|---|
|
Rey Auditory Verbal Learning Test (RAVLT)
Phase 2 - Week 8
|
49.8 units on a scale
Standard Deviation 20.2
|
59.0 units on a scale
Standard Deviation 12.3
|
|
Rey Auditory Verbal Learning Test (RAVLT)
Phase 2 - Week 16
|
57.5 units on a scale
Standard Deviation 5.9
|
61.0 units on a scale
Standard Deviation 9.5
|
|
Rey Auditory Verbal Learning Test (RAVLT)
Phase 2 - Change in Score
|
9.0 units on a scale
Standard Deviation 20.5
|
1.7 units on a scale
Standard Deviation 6.3
|
|
Rey Auditory Verbal Learning Test (RAVLT)
Phase 1 - Baseline
|
50.0 units on a scale
Standard Deviation 10.3
|
51.3 units on a scale
Standard Deviation 9.0
|
|
Rey Auditory Verbal Learning Test (RAVLT)
Phase 1 - Week 8
|
53.3 units on a scale
Standard Deviation 12.1
|
54.5 units on a scale
Standard Deviation 14.4
|
|
Rey Auditory Verbal Learning Test (RAVLT)
Phase 1 - Change in Score
|
2.9 units on a scale
Standard Deviation 10.2
|
1.8 units on a scale
Standard Deviation 13.7
|
SECONDARY outcome
Timeframe: Phase 1 timeframe is Baseline to Week 8; Phase 2 timeframe is Week 8 to Week 16Population: Due to the methods used in Sequential Parallel Comparison Design (SPCD), Phase 2 analysis only includes participants who were placebo non-responders in Phase 1. The total number of participants who received pregnenolone in Phase 1 was 26 and the total number of participants who received placebo in Phase 1 was 47. Those who received pregnenolone in Phase 1 continued to receive Pregnenolone in Phase 2. Placebo responders in Phase 1 continued to receive placebo in Phase 2.
The Trail Making Test (TMT) is a diagnostic tool measuring executive functioning and information processing in which the participant is asked to link a set of randomly distributed numbered and lettered points. Participant age, years of education, and sex are used to calculate t-scores. T-scores represent how an individual score compares to the mean / average score of that participant's demographic group. Higher t-scores indicate a faster time in connecting the set of numbers and letters compared to the average score.
Outcome measures
| Measure |
Pregnenolone
n=26 Participants
Participants randomized to receive pregnenolone in Phase 1 continued to receive pregnenolone in Phase 2. The titration schedule was as follows: 50mg BID for 7 days at Baseline, 150mg BID for 7 days at Week 1, 250mg BID for 14 days at Week 2, and 250mg BID for 28 days at Week 4. Participants continued 250mg BID throughout Phase 2. At Week 16, participants titrated down at 150mg BID for 4 days and then 50mg BID for 4 days before discontinuing.
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Placebo
n=47 Participants
Participants received placebo at the same frequency as those who received pregnenolone. Placebo responders in Phase 1 continued to received placebo in Phase 2. Placebo non-responders in Phase 1 were rerandomized to receive either placebo or pregnenolone in Phase 2.
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|---|---|---|
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Trail Making Test (TMT)
Phase 1 - Baseline
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46.6 units on a scale
Standard Deviation 11.4
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51.5 units on a scale
Standard Deviation 10.3
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Trail Making Test (TMT)
Phase 1 - Week 8
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56.6 units on a scale
Standard Deviation 15.6
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54.1 units on a scale
Standard Deviation 10.7
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Trail Making Test (TMT)
Phase 1 - Change in Score
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8.3 units on a scale
Standard Deviation 8.5
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1.1 units on a scale
Standard Deviation 9.8
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Trail Making Test (TMT)
Phase 2 - Week 8
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50.1 units on a scale
Standard Deviation 9.5
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51.0 units on a scale
Standard Deviation 8.2
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Trail Making Test (TMT)
Phase 2 - Week 16
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56.8 units on a scale
Standard Deviation 12.7
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55.3 units on a scale
Standard Deviation 9.2
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Trail Making Test (TMT)
Phase 2 - Change in Score
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3.8 units on a scale
Standard Deviation 12.6
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5.2 units on a scale
Standard Deviation 1.8
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Adverse Events
Phase 1: Placebo
Serious events: 1 serious events
Other events: 20 other events
Deaths: 0 deaths
Phase 1: Pregnenolone
Serious events: 0 serious events
Other events: 17 other events
Deaths: 0 deaths
Phase 2: Placebo
Serious events: 1 serious events
Other events: 5 other events
Deaths: 0 deaths
Phase 2: Pregnenolone
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Phase 1: Placebo
n=47 participants at risk
This group contains all participants who were randomized to receive Placebo in Phase 1.
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Phase 1: Pregnenolone
n=26 participants at risk
This group contains all participants who were randomized to receive Pregnenolone in Phase 1.
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Phase 2: Placebo
n=24 participants at risk
This group contains all participants who were randomized to receive Placebo in Phase 2.
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Phase 2: Pregnenolone
n=25 participants at risk
This group contains all participants who were randomized to receive Pregnenolone in Phase 2.
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|---|---|---|---|---|
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Infections and infestations
Implant Infection
|
2.1%
1/47 • Number of events 1 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
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0.00%
0/26 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
0.00%
0/24 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
0.00%
0/25 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
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Nervous system disorders
Stroke
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0.00%
0/47 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
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0.00%
0/26 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
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4.2%
1/24 • Number of events 1 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
0.00%
0/25 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
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Other adverse events
| Measure |
Phase 1: Placebo
n=47 participants at risk
This group contains all participants who were randomized to receive Placebo in Phase 1.
|
Phase 1: Pregnenolone
n=26 participants at risk
This group contains all participants who were randomized to receive Pregnenolone in Phase 1.
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Phase 2: Placebo
n=24 participants at risk
This group contains all participants who were randomized to receive Placebo in Phase 2.
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Phase 2: Pregnenolone
n=25 participants at risk
This group contains all participants who were randomized to receive Pregnenolone in Phase 2.
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|---|---|---|---|---|
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Gastrointestinal disorders
Constipation
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6.4%
3/47 • Number of events 3 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
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7.7%
2/26 • Number of events 2 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
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8.3%
2/24 • Number of events 4 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
0.00%
0/25 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
|
Nervous system disorders
Difficulty Falling Asleep
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6.4%
3/47 • Number of events 3 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
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7.7%
2/26 • Number of events 2 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
4.2%
1/24 • Number of events 1 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
0.00%
0/25 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
|
Gastrointestinal disorders
Dry Mouth
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14.9%
7/47 • Number of events 7 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
15.4%
4/26 • Number of events 4 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
4.2%
1/24 • Number of events 1 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
4.0%
1/25 • Number of events 1 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
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Nervous system disorders
Headache
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19.1%
9/47 • Number of events 10 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
19.2%
5/26 • Number of events 5 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
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16.7%
4/24 • Number of events 4 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
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16.0%
4/25 • Number of events 5 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
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Reproductive system and breast disorders
Premenstrual Syndrome
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6.4%
3/47 • Number of events 3 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
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3.8%
1/26 • Number of events 1 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
4.2%
1/24 • Number of events 1 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
4.0%
1/25 • Number of events 1 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
|
Ear and labyrinth disorders
Ringing in Ear
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6.4%
3/47 • Number of events 3 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
7.7%
2/26 • Number of events 2 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
0.00%
0/24 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
0.00%
0/25 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
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Gastrointestinal disorders
Diarrhea
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2.1%
1/47 • Number of events 1 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
7.7%
2/26 • Number of events 2 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
8.3%
2/24 • Number of events 2 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
0.00%
0/25 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
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Cardiac disorders
Heart Palpitations
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0.00%
0/47 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
7.7%
2/26 • Number of events 2 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
0.00%
0/24 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
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0.00%
0/25 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
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General disorders
Increased Fatigue
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0.00%
0/47 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
7.7%
2/26 • Number of events 2 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
0.00%
0/24 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
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0.00%
0/25 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
|
Gastrointestinal disorders
Increased Flatulence
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4.3%
2/47 • Number of events 2 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
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11.5%
3/26 • Number of events 3 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
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4.2%
1/24 • Number of events 1 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
4.0%
1/25 • Number of events 1 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
|
Gastrointestinal disorders
Nausea
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4.3%
2/47 • Number of events 2 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
15.4%
4/26 • Number of events 4 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
4.2%
1/24 • Number of events 1 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
4.0%
1/25 • Number of events 1 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
|
Nervous system disorders
Nightmares
|
0.00%
0/47 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
11.5%
3/26 • Number of events 3 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
0.00%
0/24 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
0.00%
0/25 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
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Gastrointestinal disorders
Stomach Pain
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0.00%
0/47 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
0.00%
0/26 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
8.3%
2/24 • Number of events 2 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
0.00%
0/25 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
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Gastrointestinal disorders
Bloating
|
2.1%
1/47 • Number of events 1 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
0.00%
0/26 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
0.00%
0/24 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
8.0%
2/25 • Number of events 3 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
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General disorders
Hot Flashes
|
0.00%
0/47 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
0.00%
0/26 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
4.2%
1/24 • Number of events 1 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
8.0%
2/25 • Number of events 2 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
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Renal and urinary disorders
Increased Urinary Frequency
|
4.3%
2/47 • Number of events 2 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
0.00%
0/26 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
0.00%
0/24 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
|
8.0%
2/25 • Number of events 2 • The period of observation for the collection of adverse events extends from the time the subject gave informed consent until the final visit at Week 16.
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Additional Information
Dr. E. Sherwood Brown
University of Texas Southwestern Medical Center
Phone: 214-645-6950
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place