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Valproate in Late Life Schizophrenia

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ClinicalTrials.gov Identifier: NCT00194025
Recruitment Status : Completed
First Posted : September 19, 2005
Results First Posted : March 1, 2011
Last Update Posted : January 6, 2015
Sponsor:
Collaborator:
Abbott
Information provided by:
University Hospitals Cleveland Medical Center

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Schizophrenia
Intervention Drug: Valproate
Enrollment 20
Recruitment Details The study was conducted at an academic psychiatry clinic in the mid-western United States. Data was collected from participants from February 2004 to November 2006. Participants were recruited in response to self-referrals from advertisements and by referrals from mental health practitioners.
Pre-assignment Details  
Arm/Group Title Valproate
Hide Arm/Group Description Enrolled individuals received adjunctive, openlabel valproate semisodium, initially started as valproate semisodium delayed-release 250 mg at bedtime for two weeks, then changed to valproate semisodium extended-release 500 mg at bedtime. Medication was administered on an outpatient/ambulatory basis, and adjusted as tolerated to target serum levels of 50- 100 mg/mL. In cases where sedation or other side effects occurred, dosage was reduced. Valproate semisodium was prescribed in a single dose at bedtime.
Period Title: Overall Study
Started 20 [1]
Completed 15 [2]
Not Completed 5
Reason Not Completed
Adverse Event             1
non-adherence with study medication             4
[1]
The intent-to-treat population received at least one dose of valproate semisodium.
[2]
5 participants withdrew prematurely
Arm/Group Title Valproate
Hide Arm/Group Description Enrolled individuals received adjunctive, openlabel valproate semisodium, initially started as valproate semisodium delayed-release 250 mg at bedtime for two weeks, then changed to valproate semisodium extended-release 500 mg at bedtime. Medication was administered on an outpatient/ambulatory basis, and adjusted as tolerated to target serum levels of 50- 100 mg/mL. In cases where sedation or other side effects occurred, dosage was reduced. Valproate semisodium was prescribed in a single dose at bedtime.
Overall Number of Baseline Participants 20
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants
<=18 years
0
   0.0%
Between 18 and 65 years
15
  75.0%
>=65 years
5
  25.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 20 participants
61.1  (9.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants
Female
16
  80.0%
Male
4
  20.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 20 participants
20
1.Primary Outcome
Title Change in Schizophrenia Psychopathology as Assessed by the Positive and Negative Symptom Scale (PANSS)
Hide Description The best and worst possible overall PANSS scores are 30 and 210 units on a scale, respectively.
Time Frame Baseline to 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Last Observation Carried Forward (LOCF) was used as the imputation technique.
Arm/Group Title Valproate
Hide Arm/Group Description:
Enrolled individuals received adjunctive, openlabel valproate semisodium, initially started as valproate semisodium delayed-release 250 mg at bedtime for two weeks, then changed to valproate semisodium extended-release 500 mg at bedtime. Medication was administered on an outpatient/ambulatory basis, and adjusted as tolerated to target serum levels of 50- 100 mg/mL. In cases where sedation or other side effects occurred, dosage was reduced. Valproate semisodium was prescribed in a single dose at bedtime.
Overall Number of Participants Analyzed 20
Mean (Standard Deviation)
Unit of Measure: scores on a scale
-17.45  (14.87)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Valproate
Comments The 1 sided t-test was applied to the scores at baseline vs. the scores at 12 weeks.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
2.Secondary Outcome
Title Change in Cognitive Status as Measured by the Mini-mental State Examination (MMSE)
Hide Description The best and worst possible overall scores are 31 and 0 units on a scale, respectively.
Time Frame Baseline to 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Last Observation Carried Forward (LOCF) was used as the imputation technique.
Arm/Group Title Valproate
Hide Arm/Group Description:
Enrolled individuals received adjunctive, openlabel valproate semisodium, initially started as valproate semisodium delayed-release 250 mg at bedtime for two weeks, then changed to valproate semisodium extended-release 500 mg at bedtime. Medication was administered on an outpatient/ambulatory basis, and adjusted as tolerated to target serum levels of 50- 100 mg/mL. In cases where sedation or other side effects occurred, dosage was reduced. Valproate semisodium was prescribed in a single dose at bedtime.
Overall Number of Participants Analyzed 20
Mean (Standard Deviation)
Unit of Measure: scores on a scale
0.4  (3.218)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Valproate
Comments The 1 sided t-test was applied to the scores at baseline vs. the scores at 12 weeks.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.585
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
3.Secondary Outcome
Title Change in Overall Functioning as Measured by the Global Assessment Scale (GAS)
Hide Description The best and worst possible GAS scores are 100 and 1 units on a scale, respectively.
Time Frame Baseline to 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Last Observation Carried Forward (LOCF) was used as the imputation technique.
Arm/Group Title Valproate
Hide Arm/Group Description:
Enrolled individuals received adjunctive, openlabel valproate semisodium, initially started as valproate semisodium delayed-release 250 mg at bedtime for two weeks, then changed to valproate semisodium extended-release 500 mg at bedtime. Medication was administered on an outpatient/ambulatory basis, and adjusted as tolerated to target serum levels of 50- 100 mg/mL. In cases where sedation or other side effects occurred, dosage was reduced. Valproate semisodium was prescribed in a single dose at bedtime.
Overall Number of Participants Analyzed 20
Mean (Standard Deviation)
Unit of Measure: scores on a scale
16.35  (15.09)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Valproate
Comments The 1 sided t-test was applied to the scores at baseline vs. the scores at 12 weeks.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
4.Secondary Outcome
Title Change in Depression Symptoms as Measured by the Geriatric Depression Scale (GDS)
Hide Description The best and worst possible GDS scores are 0 and 30 units on a scale, respectively.
Time Frame Baseline to 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Last Observation Carried Forward (LOCF) was used as the imputation technique.
Arm/Group Title Valproate
Hide Arm/Group Description:
Enrolled individuals received adjunctive, openlabel valproate semisodium, initially started as valproate semisodium delayed-release 250 mg at bedtime for two weeks, then changed to valproate semisodium extended-release 500 mg at bedtime. Medication was administered on an outpatient/ambulatory basis, and adjusted as tolerated to target serum levels of 50- 100 mg/mL. In cases where sedation or other side effects occurred, dosage was reduced. Valproate semisodium was prescribed in a single dose at bedtime.
Overall Number of Participants Analyzed 18
Mean (Standard Deviation)
Unit of Measure: scores on a scale
-1.556  (2.502)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Valproate
Comments The 1 sided t-test was applied to the scores at baseline vs. the scores at 12 weeks.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.017
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
5.Secondary Outcome
Title Change in Overall Mental Health Status as Measure by the Mental Composite Score (MCS) Subscale of the Short Form 36 Health Survey (SF-36)
Hide Description The best and worst possible MCS scores are 100 and 1 units on a scale, respectively.
Time Frame Baseline to 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The number of participants for analysis was based on available data. Last Observation Carried Forward (LOCF) was used as the imputation technique.
Arm/Group Title Valproate
Hide Arm/Group Description:
Enrolled individuals received adjunctive, openlabel valproate semisodium, initially started as valproate semisodium delayed-release 250 mg at bedtime for two weeks, then changed to valproate semisodium extended-release 500 mg at bedtime. Medication was administered on an outpatient/ambulatory basis, and adjusted as tolerated to target serum levels of 50- 100 mg/mL. In cases where sedation or other side effects occurred, dosage was reduced. Valproate semisodium was prescribed in a single dose at bedtime.
Overall Number of Participants Analyzed 14
Mean (Standard Deviation)
Unit of Measure: scores on a scale
5.298  (7.968)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Valproate
Comments The 1 sided t-test was applied to the scores at baseline vs. the scores at 12 weeks.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.027
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
6.Secondary Outcome
Title Change in Physical Health Status as Measure by the Physical Composite Score (PCS) Subscale of the Short Form 36 Health Survey (SF-36)
Hide Description The best and worst possible PCS scores are 100 and 0 units on a scale, respectively.
Time Frame Baseline to 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Last Observation Carried Forward (LOCF) was used as the imputation technique.
Arm/Group Title Valproate
Hide Arm/Group Description:
Enrolled individuals received adjunctive, openlabel valproate semisodium, initially started as valproate semisodium delayed-release 250 mg at bedtime for two weeks, then changed to valproate semisodium extended-release 500 mg at bedtime. Medication was administered on an outpatient/ambulatory basis, and adjusted as tolerated to target serum levels of 50- 100 mg/mL. In cases where sedation or other side effects occurred, dosage was reduced. Valproate semisodium was prescribed in a single dose at bedtime.
Overall Number of Participants Analyzed 14
Mean (Standard Deviation)
Unit of Measure: scores on a scale
0.932  (5.971)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Valproate
Comments The 1 sided t-test was applied to the scores at baseline vs. the scores at 12 weeks.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.569
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
7.Secondary Outcome
Title Change in Extrapyramidal Symptoms as Assessed by the Abnormal Involuntary Movement Scale (AIMS)
Hide Description The best and worst possible overall scores are 0 and 28 units on a scale, respectively.
Time Frame Baseline to 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Last Observation Carried Forward (LOCF) was used as the imputation technique.
Arm/Group Title Valproate
Hide Arm/Group Description:
Enrolled individuals received adjunctive, openlabel valproate semisodium, initially started as valproate semisodium delayed-release 250 mg at bedtime for two weeks, then changed to valproate semisodium extended-release 500 mg at bedtime. Medication was administered on an outpatient/ambulatory basis, and adjusted as tolerated to target serum levels of 50- 100 mg/mL. In cases where sedation or other side effects occurred, dosage was reduced. Valproate semisodium was prescribed in a single dose at bedtime.
Overall Number of Participants Analyzed 19
Mean (Standard Deviation)
Unit of Measure: scores on a scale
-2.105  (4.108)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Valproate
Comments The 1 sided t-test was applied to the scores at baseline vs. the scores at 12 weeks.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.038
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
8.Secondary Outcome
Title Change in Extrapyramidal Symptoms as Assessed by the Simpson Angus Neurological Rating Scale (SAS)
Hide Description The best and worst possible overall scores are 40 and 0 units on a scale, respectively.
Time Frame Baseline to 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Last Observation Carried Forward (LOCF) was used as the imputation technique.
Arm/Group Title Valproate
Hide Arm/Group Description:
Enrolled individuals received adjunctive, openlabel valproate semisodium, initially started as valproate semisodium delayed-release 250 mg at bedtime for two weeks, then changed to valproate semisodium extended-release 500 mg at bedtime. Medication was administered on an outpatient/ambulatory basis, and adjusted as tolerated to target serum levels of 50- 100 mg/mL. In cases where sedation or other side effects occurred, dosage was reduced. Valproate semisodium was prescribed in a single dose at bedtime.
Overall Number of Participants Analyzed 15
Mean (Standard Deviation)
Unit of Measure: scores on a scale
-0.6  (1.724)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Valproate
Comments The 1 sided t-test was applied to the scores at baseline vs. the scores at 12 weeks.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.199
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
9.Secondary Outcome
Title Tolerability as Assessed by Weight Change
Hide Description [Not Specified]
Time Frame Baseline to 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All available data was used implementing LOCF.
Arm/Group Title Valproate
Hide Arm/Group Description:
Enrolled individuals received adjunctive, openlabel valproate semisodium, initially started as valproate semisodium delayed-release 250 mg at bedtime for two weeks, then changed to valproate semisodium extended-release 500 mg at bedtime. Medication was administered on an outpatient/ambulatory basis, and adjusted as tolerated to target serum levels of 50- 100 mg/mL. In cases where sedation or other side effects occurred, dosage was reduced. Valproate semisodium was prescribed in a single dose at bedtime.
Overall Number of Participants Analyzed 18
Mean (Standard Deviation)
Unit of Measure: kilograms
1.1  (3.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Valproate
Comments The t-test was applied to the values at baseline vs. the values at 12 weeks.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.21
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
10.Secondary Outcome
Title Tolerability as Measured by Mean Serum Level at Study Endpoint
Hide Description [Not Specified]
Time Frame Baseline to 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Last Observation Carried Forward (LOCF) was used as the imputation technique.
Arm/Group Title Valproate
Hide Arm/Group Description:
Enrolled individuals received adjunctive, openlabel valproate semisodium, initially started as valproate semisodium delayed-release 250 mg at bedtime for two weeks, then changed to valproate semisodium extended-release 500 mg at bedtime. Medication was administered on an outpatient/ambulatory basis, and adjusted as tolerated to target serum levels of 50- 100 mg/mL. In cases where sedation or other side effects occurred, dosage was reduced. Valproate semisodium was prescribed in a single dose at bedtime.
Overall Number of Participants Analyzed 20
Mean (Standard Deviation)
Unit of Measure: ug/mL
40.86  (25.29)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Valproate
Hide Arm/Group Description Enrolled individuals received adjunctive, openlabel valproate semisodium, initially started as valproate semisodium delayed-release 250 mg at bedtime for two weeks, then changed to valproate semisodium extended-release 500 mg at bedtime. Medication was administered on an outpatient/ambulatory basis, and adjusted as tolerated to target serum levels of 50- 100 mg/mL. In cases where sedation or other side effects occurred, dosage was reduced. Valproate semisodium was prescribed in a single dose at bedtime.
All-Cause Mortality
Valproate
Affected / at Risk (%)
Total   --/-- 
Hide Serious Adverse Events
Valproate
Affected / at Risk (%)
Total   0/20 (0.00%) 
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Valproate
Affected / at Risk (%)
Total   0/20 (0.00%) 
The findings of this study must be interpreted cautiously given the limitations of small sample size, open-label, add-on design and lack of a control or comparator group. The mean age of 61 years is not representative of the "old-old" populations.
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: Martha Sajatovic MD
Organization: Case Western Reserve University and Unversity Hospitals Case Medical Center
Phone: 216-844-2808
EMail: martha.sajatovic@uhhospitals.org
Layout table for additonal information
Responsible Party: Martha Sajatovic MD, Case Western Reserve University
ClinicalTrials.gov Identifier: NCT00194025    
Other Study ID Numbers: 10850-01-L0348
First Submitted: September 13, 2005
First Posted: September 19, 2005
Results First Submitted: January 26, 2009
Results First Posted: March 1, 2011
Last Update Posted: January 6, 2015