Trial Outcomes & Findings for Pilot Study of Pregnenolone Augmentation Targeting Cognitive Symptoms in Persistently Symptomatic Patients With Schizophrenia (NCT NCT00560937)
NCT ID: NCT00560937
Last Updated: 2015-08-25
Results Overview
The SANS assesses negative symptoms in schizophrenia. The SANS consists of 21 clinical interview questions assessing negative symptoms of schizophrenia. Each question is rated on a scale of 0 (no symptoms) to 7 (severe symptoms).
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
28 participants
Primary outcome timeframe
SANS scores at baseline and 8 weeks post-randomization (at least 4 weeks; last observation carried forward)
Results posted on
2015-08-25
Participant Flow
Patient recruitment occurred between 8-05 and 4-06 for this single-site study at the Durham VAMC, Durham, NC.
Following the screening visit, patients were withdrawn during the placebo lead-in phase and were not randomized for the following reasons: 1. hyponatremia, 2. hospitalization, 3.pneumonia, 4.no show for follow-up study visit, 5.chest pain, 6. elevated prolactin at baseline, 7.prolonged QTc at baseline
Participant milestones
| Measure |
Pregnenolone
* Pregnenolone 100 mg in divided doses (50 mg BID) for 2 weeks, then
* Pregnenolone 300 mg in divided doses (150 mg BID) for 2 weeks, then
* Pregnenolone 500 mg in divided doses (250 mg BID) for 4 weeks.
|
Placebo
Placebo dosing and tablets were identical to Pregnenolone.
|
|---|---|---|
|
Overall Study
STARTED
|
10
|
11
|
|
Overall Study
COMPLETED
|
9
|
9
|
|
Overall Study
NOT COMPLETED
|
1
|
2
|
Reasons for withdrawal
| Measure |
Pregnenolone
* Pregnenolone 100 mg in divided doses (50 mg BID) for 2 weeks, then
* Pregnenolone 300 mg in divided doses (150 mg BID) for 2 weeks, then
* Pregnenolone 500 mg in divided doses (250 mg BID) for 4 weeks.
|
Placebo
Placebo dosing and tablets were identical to Pregnenolone.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
|
Overall Study
Physician Decision
|
1
|
1
|
Baseline Characteristics
Pilot Study of Pregnenolone Augmentation Targeting Cognitive Symptoms in Persistently Symptomatic Patients With Schizophrenia
Baseline characteristics by cohort
| Measure |
Pregnenolone
n=10 Participants
* Pregnenolone 100 mg in divided doses (50 mg BID) for 2 weeks, then
* Pregnenolone 300 mg in divided doses (150 mg BID) for 2 weeks, then
* Pregnenolone 500 mg in divided doses (250 mg BID) for 4 weeks.
|
Placebo
n=11 Participants
Placebo dosing and tablets were identical to Pregnenolone.
|
Total
n=21 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0.0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
10 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
21.0 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0.0 Participants
n=5 Participants
|
|
Age, Continuous
|
53 years
STANDARD_DEVIATION 6 • n=5 Participants
|
49 years
STANDARD_DEVIATION 12 • n=7 Participants
|
51 years
STANDARD_DEVIATION 9 • n=5 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2.0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
19.0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
10 participants
n=5 Participants
|
11 participants
n=7 Participants
|
21.0 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: SANS scores at baseline and 8 weeks post-randomization (at least 4 weeks; last observation carried forward)Population: Pilot proof of concept study
The SANS assesses negative symptoms in schizophrenia. The SANS consists of 21 clinical interview questions assessing negative symptoms of schizophrenia. Each question is rated on a scale of 0 (no symptoms) to 7 (severe symptoms).
Outcome measures
| Measure |
Pregnenolone
n=8 Participants
* Pregnenolone 100 mg in divided doses (50 mg BID) for 2 weeks, then
* Pregnenolone 300 mg in divided doses (150 mg BID) for 2 weeks, then
* Pregnenolone 500 mg in divided doses (250 mg BID) for 4 weeks.
|
Placebo
n=9 Participants
Placebo dosing and tablets were identical to Pregnenolone.
|
|---|---|---|
|
Mean Score on the Scale for the Assessment of Negative Symptoms (SANS), p=0.048
|
-10.38 units on a scale
Standard Deviation 10.18
|
-2.33 units on a scale
Standard Deviation 4.42
|
PRIMARY outcome
Timeframe: Change in composite BACS scores at baseline and 8 weeks post-randomization (at least 4 weeks; last observation carried forward)The BACS includes brief assessments of executive functions, verbal fluency, attention, verbal memory, working memory and motor speed. Z-scores are calculated from composite scores. Higher z-scores are indicative of better cognitive performance, lower z-scores are indicative of lower cognitive performance. Range of z-scores anticipated to be between -3 and 3.
Outcome measures
| Measure |
Pregnenolone
n=9 Participants
* Pregnenolone 100 mg in divided doses (50 mg BID) for 2 weeks, then
* Pregnenolone 300 mg in divided doses (150 mg BID) for 2 weeks, then
* Pregnenolone 500 mg in divided doses (250 mg BID) for 4 weeks.
|
Placebo
n=9 Participants
Placebo dosing and tablets were identical to Pregnenolone.
|
|---|---|---|
|
Mean Change of Z-scores on the Brief Assessment of Cognition in Schizophrenia (BACS)
|
0.60 units on a scale
Standard Deviation 0.78
|
0.22 units on a scale
Standard Deviation 0.47
|
PRIMARY outcome
Timeframe: Change in composite MATRICS scores at baseline and 8 weeks post-randomization (at least 4 weeks; last observation carried forward)The MATRICS is a battery for the assessment of cognitive symptoms in patients with schizophrenia. Composite T-scores are calculated (T-score ranges are -20 to +80, and are normed on gender and age). Higher scores are indicative of better cognitive performance, lower scores are indicative of poorer cognitive performance.
Outcome measures
| Measure |
Pregnenolone
n=9 Participants
* Pregnenolone 100 mg in divided doses (50 mg BID) for 2 weeks, then
* Pregnenolone 300 mg in divided doses (150 mg BID) for 2 weeks, then
* Pregnenolone 500 mg in divided doses (250 mg BID) for 4 weeks.
|
Placebo
n=9 Participants
Placebo dosing and tablets were identical to Pregnenolone.
|
|---|---|---|
|
Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS)
|
7.00 units on a scale
Standard Deviation 8.87
|
7.00 units on a scale
Standard Deviation 4.95
|
SECONDARY outcome
Timeframe: Change in CDSS scores at baseline and 8 weeks (at least 4 weeks; last observation carried forward)The CDSS is used measure to investigate depressive symptoms in schizophrenia. The measure includes 9 questions ranked from 0 (no symptoms) to 3 (severe symptoms). Range of possible scores: 0-27.
Outcome measures
| Measure |
Pregnenolone
n=9 Participants
* Pregnenolone 100 mg in divided doses (50 mg BID) for 2 weeks, then
* Pregnenolone 300 mg in divided doses (150 mg BID) for 2 weeks, then
* Pregnenolone 500 mg in divided doses (250 mg BID) for 4 weeks.
|
Placebo
n=9 Participants
Placebo dosing and tablets were identical to Pregnenolone.
|
|---|---|---|
|
Mean Score Change in Calgary Depression Scale for Schizophrenia (CDSS)
|
-1.57 units on a scale
Standard Deviation 2.15
|
-2.00 units on a scale
Standard Deviation 3.66
|
SECONDARY outcome
Timeframe: CGI-I scores at 8 weeks post-randomization (at least 4 weeks; last observation carried forward)The CGI-I is a commonly used psychiatric scale to assess overall general improvement. The CGI-I consists of one interviewer-rated question on a scale of 1-7. Lower scores are indicative of fewer symptoms; while higher scores are indicative of more symptoms.
Outcome measures
| Measure |
Pregnenolone
n=9 Participants
* Pregnenolone 100 mg in divided doses (50 mg BID) for 2 weeks, then
* Pregnenolone 300 mg in divided doses (150 mg BID) for 2 weeks, then
* Pregnenolone 500 mg in divided doses (250 mg BID) for 4 weeks.
|
Placebo
n=9 Participants
Placebo dosing and tablets were identical to Pregnenolone.
|
|---|---|---|
|
Clinical Global Impression Scale (CGI-I)
|
2.11 units on a scale
Standard Deviation 0.33
|
2.89 units on a scale
Standard Deviation 0.78
|
SECONDARY outcome
Timeframe: Change in PANSS scores at baseline and 8 weeks post-randomization (at least 4 weeks; last observation carried forward)The PANSS is a widely used measure with several subdomains, including positive symptoms, negative symptoms, and general psychopathology of schizophrenia. Lower scores are indicative of fewer symptoms; higher scores are indicative of more symptoms. Total PANSS scores range from 0-20.
Outcome measures
| Measure |
Pregnenolone
n=9 Participants
* Pregnenolone 100 mg in divided doses (50 mg BID) for 2 weeks, then
* Pregnenolone 300 mg in divided doses (150 mg BID) for 2 weeks, then
* Pregnenolone 500 mg in divided doses (250 mg BID) for 4 weeks.
|
Placebo
n=9 Participants
Placebo dosing and tablets were identical to Pregnenolone.
|
|---|---|---|
|
Mean Score on the Positive and Negative Symptom Scale (PANSS)
|
-9.88 units on a scale
Standard Deviation 9.23
|
-5.44 units on a scale
Standard Deviation 5.27
|
Adverse Events
Pregnenolone
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Pregnenolone
n=9 participants at risk
* Pregnenolone 100 mg in divided doses (50 mg BID) for 2 weeks, then
* Pregnenolone 300 mg in divided doses (150 mg BID) for 2 weeks, then
* Pregnenolone 500 mg in divided doses (250 mg BID) for 4 weeks.
|
Placebo
n=9 participants at risk
Placebo dosing and tablets were identical to Pregnenolone.
|
|---|---|---|
|
Psychiatric disorders
Disorientation (date, address, mayor, MD name)
|
22.2%
2/9 • Number of events 3 • Adverse events were recorded during each study visit (study visits occurred every two weeks, a total of 5 study visits) for the duration of the 10 week study (following a 2 week placebo lead-in).
Hillside Adverse Event Questionnaire used to obtain Adverse Events.
|
22.2%
2/9 • Number of events 2 • Adverse events were recorded during each study visit (study visits occurred every two weeks, a total of 5 study visits) for the duration of the 10 week study (following a 2 week placebo lead-in).
Hillside Adverse Event Questionnaire used to obtain Adverse Events.
|
|
General disorders
Decreased interest in sex
|
11.1%
1/9 • Number of events 3 • Adverse events were recorded during each study visit (study visits occurred every two weeks, a total of 5 study visits) for the duration of the 10 week study (following a 2 week placebo lead-in).
Hillside Adverse Event Questionnaire used to obtain Adverse Events.
|
22.2%
2/9 • Number of events 3 • Adverse events were recorded during each study visit (study visits occurred every two weeks, a total of 5 study visits) for the duration of the 10 week study (following a 2 week placebo lead-in).
Hillside Adverse Event Questionnaire used to obtain Adverse Events.
|
|
Cardiac disorders
Hypertension
|
11.1%
1/9 • Number of events 2 • Adverse events were recorded during each study visit (study visits occurred every two weeks, a total of 5 study visits) for the duration of the 10 week study (following a 2 week placebo lead-in).
Hillside Adverse Event Questionnaire used to obtain Adverse Events.
|
11.1%
1/9 • Number of events 3 • Adverse events were recorded during each study visit (study visits occurred every two weeks, a total of 5 study visits) for the duration of the 10 week study (following a 2 week placebo lead-in).
Hillside Adverse Event Questionnaire used to obtain Adverse Events.
|
|
General disorders
Impaired sexual performance
|
0.00%
0/9 • Adverse events were recorded during each study visit (study visits occurred every two weeks, a total of 5 study visits) for the duration of the 10 week study (following a 2 week placebo lead-in).
Hillside Adverse Event Questionnaire used to obtain Adverse Events.
|
11.1%
1/9 • Number of events 3 • Adverse events were recorded during each study visit (study visits occurred every two weeks, a total of 5 study visits) for the duration of the 10 week study (following a 2 week placebo lead-in).
Hillside Adverse Event Questionnaire used to obtain Adverse Events.
|
|
General disorders
Excitation/agitation
|
0.00%
0/9 • Adverse events were recorded during each study visit (study visits occurred every two weeks, a total of 5 study visits) for the duration of the 10 week study (following a 2 week placebo lead-in).
Hillside Adverse Event Questionnaire used to obtain Adverse Events.
|
11.1%
1/9 • Number of events 4 • Adverse events were recorded during each study visit (study visits occurred every two weeks, a total of 5 study visits) for the duration of the 10 week study (following a 2 week placebo lead-in).
Hillside Adverse Event Questionnaire used to obtain Adverse Events.
|
|
General disorders
Dry Mouth
|
11.1%
1/9 • Number of events 2 • Adverse events were recorded during each study visit (study visits occurred every two weeks, a total of 5 study visits) for the duration of the 10 week study (following a 2 week placebo lead-in).
Hillside Adverse Event Questionnaire used to obtain Adverse Events.
|
11.1%
1/9 • Number of events 1 • Adverse events were recorded during each study visit (study visits occurred every two weeks, a total of 5 study visits) for the duration of the 10 week study (following a 2 week placebo lead-in).
Hillside Adverse Event Questionnaire used to obtain Adverse Events.
|
|
General disorders
Malaise
|
0.00%
0/9 • Adverse events were recorded during each study visit (study visits occurred every two weeks, a total of 5 study visits) for the duration of the 10 week study (following a 2 week placebo lead-in).
Hillside Adverse Event Questionnaire used to obtain Adverse Events.
|
11.1%
1/9 • Number of events 1 • Adverse events were recorded during each study visit (study visits occurred every two weeks, a total of 5 study visits) for the duration of the 10 week study (following a 2 week placebo lead-in).
Hillside Adverse Event Questionnaire used to obtain Adverse Events.
|
|
Eye disorders
Blurred Vision
|
0.00%
0/9 • Adverse events were recorded during each study visit (study visits occurred every two weeks, a total of 5 study visits) for the duration of the 10 week study (following a 2 week placebo lead-in).
Hillside Adverse Event Questionnaire used to obtain Adverse Events.
|
11.1%
1/9 • Number of events 1 • Adverse events were recorded during each study visit (study visits occurred every two weeks, a total of 5 study visits) for the duration of the 10 week study (following a 2 week placebo lead-in).
Hillside Adverse Event Questionnaire used to obtain Adverse Events.
|
|
General disorders
Restlessness
|
22.2%
2/9 • Number of events 5 • Adverse events were recorded during each study visit (study visits occurred every two weeks, a total of 5 study visits) for the duration of the 10 week study (following a 2 week placebo lead-in).
Hillside Adverse Event Questionnaire used to obtain Adverse Events.
|
0.00%
0/9 • Adverse events were recorded during each study visit (study visits occurred every two weeks, a total of 5 study visits) for the duration of the 10 week study (following a 2 week placebo lead-in).
Hillside Adverse Event Questionnaire used to obtain Adverse Events.
|
|
Musculoskeletal and connective tissue disorders
Muscle pain/stiffness
|
11.1%
1/9 • Number of events 1 • Adverse events were recorded during each study visit (study visits occurred every two weeks, a total of 5 study visits) for the duration of the 10 week study (following a 2 week placebo lead-in).
Hillside Adverse Event Questionnaire used to obtain Adverse Events.
|
0.00%
0/9 • Adverse events were recorded during each study visit (study visits occurred every two weeks, a total of 5 study visits) for the duration of the 10 week study (following a 2 week placebo lead-in).
Hillside Adverse Event Questionnaire used to obtain Adverse Events.
|
|
Cardiac disorders
Cold extremities
|
11.1%
1/9 • Number of events 1 • Adverse events were recorded during each study visit (study visits occurred every two weeks, a total of 5 study visits) for the duration of the 10 week study (following a 2 week placebo lead-in).
Hillside Adverse Event Questionnaire used to obtain Adverse Events.
|
0.00%
0/9 • Adverse events were recorded during each study visit (study visits occurred every two weeks, a total of 5 study visits) for the duration of the 10 week study (following a 2 week placebo lead-in).
Hillside Adverse Event Questionnaire used to obtain Adverse Events.
|
Additional Information
Christine E. Marx, MD, MA
Durham Veterans Affairs Medical Center
Phone: 919 286-0411
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place