Trial Outcomes & Findings for Development of Pregnenolone as a Treatment for Depression (NCT NCT03645096)
NCT ID: NCT03645096
Last Updated: 2024-05-01
Results Overview
Determine if an increase in Amygdala-PCC functional connectivity is observed with pregnenolone as compared to placebo. Amygdala-PCC functional connectivity was measured using resting state fMRI blood-oxygen-level dependent (BOLD) response and transformed to standardized z-scores (with μ=0 and σ=1) for analysis. Functional connectivity was measured three times corresponding to three treatments (500 mg pregnenolone, 800 mg pregnenolone, and placebo). Better outcomes are represented by greater functional connectivity, and are indicated by a higher z-score at 500 mg or 800 mg, relative to that at placebo (i.e., there is no absolute threshold).
COMPLETED
PHASE1
34 participants
7 days
2024-05-01
Participant Flow
Subjects were screened for eligibility from September 2019 through November 2021 at UT Southwestern in Dallas, TX. 34 Subjects were consented by a research study coordinator in a private office within Dr. Brown's PNE Lab.
29 of 34 participants were randomized. It was determined that 5 subjects were not eligible for the study and were not randomized.
Participant milestones
| Measure |
Pregnenolone 500 > Pregnenolone 800 > Placebo
3 exposures in order:
1. Pregnenolone 500 mg capsule by mouth, daily for 7 days followed by 14 day washout.
2. Pregnenolone 800 mg capsule by mouth, daily for 7 days followed by 14 day washout.
3. Matching placebo capsule by mouth, daily for 7 days.
Pregnenolone 500 mg: Pregnenolone 500 mg capsule.
Pregnenolone 800 mg: Pregnenolone 800 mg capsule.
Placebo: Placebo capsule manufactured to mimic pregnenolone capsule.
|
Pregnenolone 500 > Placebo > Pregnenolone 800
3 exposures in order:
1. Pregnenolone 500 mg capsule by mouth, daily for 7 days followed by 14 day washout.
2. Matching placebo capsule by mouth, daily for 7 days followed by 14 day washout.
3. Pregnenolone 800 mg capsule by mouth, daily for 7 days.
Pregnenolone 500 mg: Pregnenolone 500 mg capsule.
Pregnenolone 800 mg: Pregnenolone 800 mg capsule.
Placebo: Placebo capsule manufactured to mimic pregnenolone capsule.
|
Pregnenolone 800 > Pregnenolone 500 > Placebo
3 exposures in order:
1. Pregnenolone 800 mg capsule by mouth, daily for 7 days followed by 14 day washout.
2. Pregnenolone 500 mg capsule by mouth, daily for 7 days followed by 14 day washout.
3. Matching placebo capsule by mouth, daily for 7 days.
Pregnenolone 500 mg: Pregnenolone 500 mg capsule.
Pregnenolone 800 mg: Pregnenolone 800 mg capsule.
Placebo: Placebo capsule manufactured to mimic pregnenolone capsule.
|
Pregnenolone 800 > Placebo > Pregnenolone 500
3 exposures in order:
1. Pregnenolone 800 mg capsule by mouth, daily for 7 days followed by 14 day washout.
2. Matching placebo capsule by mouth, daily for 7 days followed by 14 day washout.
3. Pregnenolone 500 mg capsule by mouth, daily for 7 days.
Pregnenolone 500 mg: Pregnenolone 500 mg capsule.
Pregnenolone 800 mg: Pregnenolone 800 mg capsule.
Placebo: Placebo capsule manufactured to mimic pregnenolone capsule.
|
Placebo > Pregnenolone 500 > Pregnenolone 800
3 exposures in order:
1. Matching placebo capsule by mouth, daily for 7 days followed by 14 day washout.
2. Pregnenolone 500 mg capsule by mouth, daily for 7 days followed by 14 day washout.
3. Pregnenolone 800 mg capsule by mouth, daily for 7 days.
Pregnenolone 500 mg: Pregnenolone 500 mg capsule.
Pregnenolone 800 mg: Pregnenolone 800 mg capsule.
Placebo: Placebo capsule manufactured to mimic pregnenolone capsule.
|
Placebo > Pregnenolone 800 > Pregnenolone 500
3 exposures in order:
1. Matching placebo capsule by mouth, daily for 7 days followed by 14 day washout.
2. Pregnenolone 800 mg capsule by mouth, daily for 7 days followed by 14 day washout.
3. Pregnenolone 500 mg capsule by mouth, daily for 7 days.
Pregnenolone 500 mg: Pregnenolone 500 mg capsule.
Pregnenolone 800 mg: Pregnenolone 800 mg capsule.
Placebo: Placebo capsule manufactured to mimic pregnenolone capsule.
|
|---|---|---|---|---|---|---|
|
First Treatment (21 Days)
STARTED
|
4
|
4
|
7
|
7
|
5
|
2
|
|
First Treatment (21 Days)
COMPLETED
|
4
|
3
|
5
|
7
|
3
|
2
|
|
First Treatment (21 Days)
NOT COMPLETED
|
0
|
1
|
2
|
0
|
2
|
0
|
|
Second Treatment (21 Days)
STARTED
|
4
|
3
|
5
|
7
|
3
|
2
|
|
Second Treatment (21 Days)
COMPLETED
|
3
|
2
|
5
|
5
|
3
|
2
|
|
Second Treatment (21 Days)
NOT COMPLETED
|
1
|
1
|
0
|
2
|
0
|
0
|
|
Third Treatment (21 Days)
STARTED
|
3
|
2
|
5
|
5
|
3
|
2
|
|
Third Treatment (21 Days)
COMPLETED
|
3
|
1
|
4
|
3
|
3
|
2
|
|
Third Treatment (21 Days)
NOT COMPLETED
|
0
|
1
|
1
|
2
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Development of Pregnenolone as a Treatment for Depression
Baseline characteristics by cohort
| Measure |
Pregnenolone 500 > Pregnenolone 800 > Placebo
n=4 Participants
3 exposures in order:
1. Pregnenolone 500 mg capsule by mouth, daily for 7 days followed by 14 day washout.
2. Pregnenolone 800 mg capsule by mouth, daily for 7 days followed by 14 day washout.
3. Matching placebo capsule by mouth, daily for 7 days.
Pregnenolone 500 mg: Pregnenolone 500 mg capsule.
Pregnenolone 800 mg: Pregnenolone 800 mg capsule.
Placebo: Placebo capsule manufactured to mimic pregnenolone capsule.
|
Pregnenolone 500 > Placebo > Pregnenolone 800
n=4 Participants
3 exposures in order:
1. Pregnenolone 500 mg capsule by mouth, daily for 7 days followed by 14 day washout.
2. Matching placebo capsule by mouth, daily for 7 days followed by 14 day washout.
3. Pregnenolone 800 mg capsule by mouth, daily for 7 days.
Pregnenolone 500 mg: Pregnenolone 500 mg capsule.
Pregnenolone 800 mg: Pregnenolone 800 mg capsule.
Placebo: Placebo capsule manufactured to mimic pregnenolone capsule.
|
Pregnenolone 800 > Pregnenolone 500 > Placebo
n=7 Participants
3 exposures in order:
1. Pregnenolone 800 mg capsule by mouth, daily for 7 days followed by 14 day washout.
2. Pregnenolone 500 mg capsule by mouth, daily for 7 days followed by 14 day washout.
3. Matching placebo capsule by mouth, daily for 7 days.
Pregnenolone 500 mg: Pregnenolone 500 mg capsule.
Pregnenolone 800 mg: Pregnenolone 800 mg capsule.
Placebo: Placebo capsule manufactured to mimic pregnenolone capsule.
|
Pregnenolone 800 > Placebo > Pregnenolone 500
n=7 Participants
3 exposures in order:
1. Pregnenolone 800 mg capsule by mouth, daily for 7 days followed by 14 day washout.
2. Matching placebo capsule by mouth, daily for 7 days followed by 14 day washout.
3. Pregnenolone 500 mg capsule by mouth, daily for 7 days.
Pregnenolone 500 mg: Pregnenolone 500 mg capsule.
Pregnenolone 800 mg: Pregnenolone 800 mg capsule.
Placebo: Placebo capsule manufactured to mimic pregnenolone capsule.
|
Placebo > Pregnenolone 500 > Pregnenolone 800
n=5 Participants
3 exposures in order:
1. Matching placebo capsule by mouth, daily for 7 days followed by 14 day washout.
2. Pregnenolone 500 mg capsule by mouth, daily for 7 days followed by 14 day washout.
3. Pregnenolone 800 mg capsule by mouth, daily for 7 days.
Pregnenolone 500 mg: Pregnenolone 500 mg capsule.
Pregnenolone 800 mg: Pregnenolone 800 mg capsule.
Placebo: Placebo capsule manufactured to mimic pregnenolone capsule.
|
Placebo > Pregnenolone 800 > Pregnenolone 500
n=2 Participants
3 exposures in order:
1. Matching placebo capsule by mouth, daily for 7 days followed by 14 day washout.
2. Pregnenolone 800 mg capsule by mouth, daily for 7 days followed by 14 day washout.
3. Pregnenolone 500 mg capsule by mouth, daily for 7 days.
Pregnenolone 500 mg: Pregnenolone 500 mg capsule.
Pregnenolone 800 mg: Pregnenolone 800 mg capsule.
Placebo: Placebo capsule manufactured to mimic pregnenolone capsule.
|
Total
n=29 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
5 Participants
n=21 Participants
|
2 Participants
n=8 Participants
|
29 Participants
n=8 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Age, Continuous
|
50.50 years
STANDARD_DEVIATION 7.19 • n=5 Participants
|
43.25 years
STANDARD_DEVIATION 16.86 • n=7 Participants
|
44.29 years
STANDARD_DEVIATION 10.94 • n=5 Participants
|
43.71 years
STANDARD_DEVIATION 11.22 • n=4 Participants
|
46.00 years
STANDARD_DEVIATION 8.40 • n=21 Participants
|
51.00 years
STANDARD_DEVIATION 1.41 • n=8 Participants
|
45.62 years
STANDARD_DEVIATION 10.31 • n=8 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
5 Participants
n=21 Participants
|
2 Participants
n=8 Participants
|
29 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
1 Participants
n=8 Participants
|
6 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
1 Participants
n=8 Participants
|
22 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
1 Participants
n=8 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
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
2 Participants
n=8 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
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
1 Participants
n=8 Participants
|
7 Participants
n=8 Participants
|
|
Race (NIH/OMB)
White
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
1 Participants
n=8 Participants
|
20 Participants
n=8 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
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Race (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
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Region of Enrollment
United States
|
4 participants
n=5 Participants
|
4 participants
n=7 Participants
|
7 participants
n=5 Participants
|
7 participants
n=4 Participants
|
5 participants
n=21 Participants
|
2 participants
n=8 Participants
|
29 participants
n=8 Participants
|
|
HAM-D
|
14.75 units on a scale
STANDARD_DEVIATION 2.50 • n=5 Participants
|
12.75 units on a scale
STANDARD_DEVIATION 4.92 • n=7 Participants
|
13.00 units on a scale
STANDARD_DEVIATION 4.28 • n=5 Participants
|
14.14 units on a scale
STANDARD_DEVIATION 5.34 • n=4 Participants
|
16.00 units on a scale
STANDARD_DEVIATION 3.81 • n=21 Participants
|
11.50 units on a scale
STANDARD_DEVIATION 7.78 • n=8 Participants
|
13.90 units on a scale
STANDARD_DEVIATION 4.39 • n=8 Participants
|
PRIMARY outcome
Timeframe: 7 daysPopulation: Some fMRI data may have been unusable due to motion in the scanner.
Determine if an increase in Amygdala-PCC functional connectivity is observed with pregnenolone as compared to placebo. Amygdala-PCC functional connectivity was measured using resting state fMRI blood-oxygen-level dependent (BOLD) response and transformed to standardized z-scores (with μ=0 and σ=1) for analysis. Functional connectivity was measured three times corresponding to three treatments (500 mg pregnenolone, 800 mg pregnenolone, and placebo). Better outcomes are represented by greater functional connectivity, and are indicated by a higher z-score at 500 mg or 800 mg, relative to that at placebo (i.e., there is no absolute threshold).
Outcome measures
| Measure |
Pregnenolone (500 mg)
n=18 Participants
Pregnenolone 500 mg capsule by mouth, daily for 7 days.
|
Pregnenolone (800 mg)
n=20 Participants
Pregnenolone 800 mg capsule by mouth, daily for 7 days.
|
Placebo
n=18 Participants
Matching placebo capsule by mouth, daily for 7 days.
|
|---|---|---|---|
|
Amygdala-PCC Functional Connectivity
|
-0.0815 z-score
Standard Deviation 0.1680
|
-0.0530 z-score
Standard Deviation 0.1715
|
-0.0456 z-score
Standard Deviation 0.1736
|
PRIMARY outcome
Timeframe: 7 daysPopulation: Some fMRI data may have been unusable due to motion in the scanner.
Determine if an increase in dlPFC-Insula functional connectivity is observed with pregnenolone as compared to placebo. dlPFC-Insula functional connectivity was measured using resting state fMRI blood-oxygen-level dependent (BOLD) response and transformed to standardized z-scores (with μ=0 and σ=1) for analysis. Functional connectivity was measured three times corresponding to three treatments (500 mg pregnenolone, 800 mg pregnenolone, and placebo). Better outcomes are represented by greater functional connectivity, and are indicated by a higher z-score at 500 mg or 800 mg, relative to that at placebo (i.e., there is no absolute threshold).
Outcome measures
| Measure |
Pregnenolone (500 mg)
n=18 Participants
Pregnenolone 500 mg capsule by mouth, daily for 7 days.
|
Pregnenolone (800 mg)
n=20 Participants
Pregnenolone 800 mg capsule by mouth, daily for 7 days.
|
Placebo
n=18 Participants
Matching placebo capsule by mouth, daily for 7 days.
|
|---|---|---|---|
|
dlPFC-Insula Functional Connectivity
|
0.0495 z-score
Standard Deviation 0.2524
|
0.1413 z-score
Standard Deviation 0.3036
|
0.0855 z-score
Standard Deviation 0.2941
|
PRIMARY outcome
Timeframe: 7 daysPopulation: All participants with available data for each treatment condition.
Determine if an increase in occipital GABA concentration is observed with pregnenolone, as compared to placebo. Occipital GABA concentration using spectroscopy with tCr reference. Higher concentration values are representative of a greater anti-depressant effect.
Outcome measures
| Measure |
Pregnenolone (500 mg)
n=17 Participants
Pregnenolone 500 mg capsule by mouth, daily for 7 days.
|
Pregnenolone (800 mg)
n=19 Participants
Pregnenolone 800 mg capsule by mouth, daily for 7 days.
|
Placebo
n=18 Participants
Matching placebo capsule by mouth, daily for 7 days.
|
|---|---|---|---|
|
GABA Concentration.
|
0.0947 millimolars (mM)
Standard Deviation 0.0294
|
0.0861 millimolars (mM)
Standard Deviation 0.0264
|
0.0974 millimolars (mM)
Standard Deviation 0.0262
|
SECONDARY outcome
Timeframe: 7 daysPopulation: All participants with available data for each treatment condition.
Assess bioavailability of pregnenolone by demonstrating increases in serum pregnenolone and allopregnanolone with pregnenolone administration. Change (increases) in blood serum pregnenolone levels are indicative of bioavailability.
Outcome measures
| Measure |
Pregnenolone (500 mg)
n=16 Participants
Pregnenolone 500 mg capsule by mouth, daily for 7 days.
|
Pregnenolone (800 mg)
n=19 Participants
Pregnenolone 800 mg capsule by mouth, daily for 7 days.
|
Placebo
n=17 Participants
Matching placebo capsule by mouth, daily for 7 days.
|
|---|---|---|---|
|
Pregnenolone Level
|
10902.60 pg/mL
Standard Deviation 11849.18
|
11484.75 pg/mL
Standard Deviation 13038.50
|
769.63 pg/mL
Standard Deviation 554.50
|
SECONDARY outcome
Timeframe: 7 daysPopulation: All participants with available data for each treatment condition.
Assess bioavailability of pregnenolone by demonstrating increases in serum pregnenolone and allopregnanolone with pregnenolone administration. Change (increases) in blood serum allopregnanolone levels are indicative of bioavailability.
Outcome measures
| Measure |
Pregnenolone (500 mg)
n=16 Participants
Pregnenolone 500 mg capsule by mouth, daily for 7 days.
|
Pregnenolone (800 mg)
n=19 Participants
Pregnenolone 800 mg capsule by mouth, daily for 7 days.
|
Placebo
n=17 Participants
Matching placebo capsule by mouth, daily for 7 days.
|
|---|---|---|---|
|
Allopregnanolone Level
|
2478.39 pg/mL
Standard Deviation 1801.67
|
2489.08 pg/mL
Standard Deviation 2180.59
|
124.22 pg/mL
Standard Deviation 224.62
|
SECONDARY outcome
Timeframe: 7 daysPopulation: All participants with available data for each treatment condition.
Assess safety and tolerability of pregnenolone at the doses tested. SAFTEE is a side effect self-report assessment scale that consists of 56 potential side effects. Participants rate how bothersome each side effect is on a scale of "none" (0), "mild" (1), "moderate" (2), "severe" (3). Total scores range from 0 to 168. A higher total score (sum of all items) indicates a higher level of side effect burden.
Outcome measures
| Measure |
Pregnenolone (500 mg)
n=20 Participants
Pregnenolone 500 mg capsule by mouth, daily for 7 days.
|
Pregnenolone (800 mg)
n=22 Participants
Pregnenolone 800 mg capsule by mouth, daily for 7 days.
|
Placebo
n=20 Participants
Matching placebo capsule by mouth, daily for 7 days.
|
|---|---|---|---|
|
Systematic Assessment for Treatment Emergent Events (SAFTEE)
|
16.15 units on a scale
Standard Deviation 12.42
|
19.14 units on a scale
Standard Deviation 12.41
|
17.60 units on a scale
Standard Deviation 9.65
|
SECONDARY outcome
Timeframe: 7 daysIdentify a dose of pregnenolone that demonstrates bioavailability (see "Pregnenolone Level" and "Allopregnanolone Level" outcome measures), tolerability (see "SAFTEE" outcome measure); and is associated with a significant change in a biosignature.
Outcome measures
| Measure |
Pregnenolone (500 mg)
n=21 Participants
Pregnenolone 500 mg capsule by mouth, daily for 7 days.
|
Pregnenolone (800 mg)
Pregnenolone 800 mg capsule by mouth, daily for 7 days.
|
Placebo
Matching placebo capsule by mouth, daily for 7 days.
|
|---|---|---|---|
|
Pregnenolone Dose
|
500 mg
|
—
|
—
|
Adverse Events
Pregnenolone 800
Pregnenolone 500
Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place