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Pilot Study of Pregnenolone Augmentation Targeting Cognitive Symptoms in Persistently Symptomatic Patients With Schizophrenia

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ClinicalTrials.gov Identifier: NCT00560937
Recruitment Status : Completed
First Posted : November 20, 2007
Results First Posted : December 28, 2010
Last Update Posted : August 25, 2015
Sponsor:
Information provided by:
Durham VA Medical Center

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Schizophrenia
Interventions Drug: Pregnenolone
Drug: Placebo
Enrollment 28
Recruitment Details Patient recruitment occurred between 8-05 and 4-06 for this single-site study at the Durham VAMC, Durham, NC.
Pre-assignment Details Following the screening visit, patients were withdrawn during the placebo lead-in phase and were not randomized for the following reasons: 1.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
Arm/Group Title Pregnenolone Placebo
Hide Arm/Group Description
  • 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 dosing and tablets were identical to Pregnenolone.
Period Title: Overall Study
Started 10 11
Completed 9 [1] 9
Not Completed 1 2
Reason Not Completed
Withdrawal by Subject             0             1
Physician Decision             1             1
[1]
One participant was withdrawn after 6 weeks and data were carried forward
Arm/Group Title Pregnenolone Placebo Total
Hide Arm/Group Description
  • 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 dosing and tablets were identical to Pregnenolone. Total of all reporting groups
Overall Number of Baseline Participants 10 11 21
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 11 participants 21 participants
<=18 years
0
   0.0%
0
   0.0%
0.0
Between 18 and 65 years
10
 100.0%
11
 100.0%
21.0
>=65 years
0
   0.0%
0
   0.0%
0.0
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 10 participants 11 participants 21 participants
53  (6) 49  (12) 51  (9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 11 participants 21 participants
Female
1
  10.0%
1
   9.1%
2.0
Male
9
  90.0%
10
  90.9%
19.0
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 10 participants 11 participants 21 participants
10 11 21
1.Primary Outcome
Title Mean Score on the Scale for the Assessment of Negative Symptoms (SANS), p=0.048
Hide Description 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).
Time Frame SANS scores at baseline and 8 weeks post-randomization (at least 4 weeks; last observation carried forward)
Hide Outcome Measure Data
Hide Analysis Population Description
Pilot proof of concept study
Arm/Group Title Pregnenolone Placebo
Hide Arm/Group Description:
  • 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 dosing and tablets were identical to Pregnenolone.
Overall Number of Participants Analyzed 8 9
Mean (Standard Deviation)
Unit of Measure: units on a scale
-10.38  (10.18) -2.33  (4.42)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pregnenolone, Placebo
Comments T-test of change scores, pregnenolone vs. placebo post-treatment compared to baseline.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .048
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
2.Primary Outcome
Title Mean Change of Z-scores on the Brief Assessment of Cognition in Schizophrenia (BACS)
Hide Description 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.
Time Frame Change in composite BACS scores at baseline and 8 weeks post-randomization (at least 4 weeks; last observation carried forward)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pregnenolone Placebo
Hide Arm/Group Description:
  • 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 dosing and tablets were identical to Pregnenolone.
Overall Number of Participants Analyzed 9 9
Mean (Standard Deviation)
Unit of Measure: units on a scale
0.60  (0.78) 0.22  (0.47)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.22
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
3.Primary Outcome
Title Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS)
Hide Description 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.
Time Frame Change in composite MATRICS scores at baseline and 8 weeks post-randomization (at least 4 weeks; last observation carried forward)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pregnenolone Placebo
Hide Arm/Group Description:
  • 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 dosing and tablets were identical to Pregnenolone.
Overall Number of Participants Analyzed 9 9
Mean (Standard Deviation)
Unit of Measure: units on a scale
7.00  (8.87) 7.00  (4.95)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pregnenolone, Placebo
Comments T-test of change scores, pregnenolone compared to placebo post-treatment vs. pre-randomization.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
4.Secondary Outcome
Title Mean Score Change in Calgary Depression Scale for Schizophrenia (CDSS)
Hide Description 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.
Time Frame Change in CDSS scores at baseline and 8 weeks (at least 4 weeks; last observation carried forward)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pregnenolone Placebo
Hide Arm/Group Description:
  • 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 dosing and tablets were identical to Pregnenolone.
Overall Number of Participants Analyzed 9 9
Mean (Standard Deviation)
Unit of Measure: units on a scale
-1.57  (2.15) -2.00  (3.66)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.79
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
5.Secondary Outcome
Title Clinical Global Impression Scale (CGI-I)
Hide Description 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.
Time Frame CGI-I scores at 8 weeks post-randomization (at least 4 weeks; last observation carried forward)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pregnenolone Placebo
Hide Arm/Group Description:
  • 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 dosing and tablets were identical to Pregnenolone.
Overall Number of Participants Analyzed 9 9
Mean (Standard Deviation)
Unit of Measure: units on a scale
2.11  (0.33) 2.89  (0.78)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.014
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
6.Secondary Outcome
Title Mean Score on the Positive and Negative Symptom Scale (PANSS)
Hide Description 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.
Time Frame Change in PANSS scores at baseline and 8 weeks post-randomization (at least 4 weeks; last observation carried forward)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pregnenolone Placebo
Hide Arm/Group Description:
  • 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 dosing and tablets were identical to Pregnenolone.
Overall Number of Participants Analyzed 9 9
Mean (Standard Deviation)
Unit of Measure: units on a scale
-9.88  (9.23) -5.44  (5.27)
Time Frame 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).
Adverse Event Reporting Description Hillside Adverse Event Questionnaire used to obtain Adverse Events.
 
Arm/Group Title Pregnenolone Placebo
Hide Arm/Group Description
  • 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 dosing and tablets were identical to Pregnenolone.
All-Cause Mortality
Pregnenolone Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Pregnenolone Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/9 (0.00%)      0/9 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Pregnenolone Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/9 (44.44%)      5/9 (55.56%)    
Cardiac disorders     
Hypertension   1/9 (11.11%)  2 1/9 (11.11%)  3
Cold extremities   1/9 (11.11%)  1 0/9 (0.00%)  0
Eye disorders     
Blurred Vision   0/9 (0.00%)  0 1/9 (11.11%)  1
General disorders     
Decreased interest in sex   1/9 (11.11%)  3 2/9 (22.22%)  3
Impaired sexual performance   0/9 (0.00%)  0 1/9 (11.11%)  3
Excitation/agitation   0/9 (0.00%)  0 1/9 (11.11%)  4
Dry Mouth   1/9 (11.11%)  2 1/9 (11.11%)  1
Malaise   0/9 (0.00%)  0 1/9 (11.11%)  1
Restlessness   2/9 (22.22%)  5 0/9 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Muscle pain/stiffness   1/9 (11.11%)  1 0/9 (0.00%)  0
Psychiatric disorders     
Disorientation (date, address, mayor, MD name)   2/9 (22.22%)  3 2/9 (22.22%)  2
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Christine E. Marx, MD, MA
Organization: Durham Veterans Affairs Medical Center
Phone: 919 286-0411 ext 7426
EMail: marx0001@mc.duke.edu
Layout table for additonal information
Responsible Party: Christine E. Marx, MD, Durham Veterans Affairs Medical Center
ClinicalTrials.gov Identifier: NCT00560937     History of Changes
Other Study ID Numbers: VA IRB# 00924
First Submitted: November 19, 2007
First Posted: November 20, 2007
Results First Submitted: March 31, 2009
Results First Posted: December 28, 2010
Last Update Posted: August 25, 2015