Valproate in Late Life Schizophrenia

• Sponsor: University Hospitals Cleveland Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00194025
• Collaborator: Abbott (Industry)
• Enrollment: 20
• Location: 1
• Arm: 1
• Duration (Months): 24
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

The purpose of this research study is to analyze the effectiveness and tolerability of a medication, valproate ( Depakote and Depakote ER), in individuals age 50 years and older who have schizophrenia.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia	Drug: Valproate	Phase 4

Detailed Description

It is known that up to 30% of individuals with schizophrenia continue to have symptoms even when treated with current FDA-approved medications intended to treat their schizophrenia. Anticonvulsant medications such as valproate (Depakote and Depakote ER) are known to be effective for related conditions such as bipolar disorder (manic depressive illness), and are also used by some physicians in clinical settings in combination with antipsychotic medications to treat symptoms of schizophrenia. Currently Depakote and Depakote ER are approved by the FDA to treat bipolar disorder and to treat seizure disorder. This study will test to see if Depakote and Depakote ER may improve symptoms of schizophrenia as well when added to antipsychotic medications.

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Add-on Valproate in Late Life Schizophrenia
• Study Start Date: Nov 1, 2004
• Actual Primary Completion Date: Nov 1, 2006
• Actual Study Completion Date: Nov 1, 2006

Arms and Interventions

Arm

Intervention/Treatment

Experimental: valproate All participants received open-label, add-on valproate.

Drug: Valproate; Enrolled individuals received adjunctive, open-label 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 µg/mL. In cases where sedation or other side effects occurred, dosage was reduced. Valproate semisodium was prescribed in a single dose at bedtime.; Other Names: Depakote Depakote ER

Outcome Measures

Primary Outcome Measures

1. Change in Schizophrenia Psychopathology as Assessed by the Positive and Negative Symptom Scale (PANSS) [Baseline to 12 weeks]

   The best and worst possible overall PANSS scores are 30 and 210 units on a scale, respectively.

Secondary Outcome Measures

1. Change in Cognitive Status as Measured by the Mini-mental State Examination (MMSE) [Baseline to 12 weeks]

   The best and worst possible overall scores are 31 and 0 units on a scale, respectively.

2. Change in Overall Functioning as Measured by the Global Assessment Scale (GAS) [Baseline to 12 weeks]

   The best and worst possible GAS scores are 100 and 1 units on a scale, respectively.

3. Change in Depression Symptoms as Measured by the Geriatric Depression Scale (GDS) [Baseline to 12 weeks]

   The best and worst possible GDS scores are 0 and 30 units on a scale, respectively.

4. Change in Overall Mental Health Status as Measure by the Mental Composite Score (MCS) Subscale of the Short Form 36 Health Survey (SF-36) [Baseline to 12 weeks]

   The best and worst possible MCS scores are 100 and 1 units on a scale, respectively.

5. Change in Physical Health Status as Measure by the Physical Composite Score (PCS) Subscale of the Short Form 36 Health Survey (SF-36) [Baseline to 12 weeks]

   The best and worst possible PCS scores are 100 and 0 units on a scale, respectively.

6. Change in Extrapyramidal Symptoms as Assessed by the Abnormal Involuntary Movement Scale (AIMS) [Baseline to 12 weeks]

   The best and worst possible overall scores are 0 and 28 units on a scale, respectively.

7. Change in Extrapyramidal Symptoms as Assessed by the Simpson Angus Neurological Rating Scale (SAS) [Baseline to 12 weeks]

   The best and worst possible overall scores are 40 and 0 units on a scale, respectively.

8. Tolerability as Assessed by Weight Change [Baseline to 12 weeks]

9. Tolerability as Measured by Mean Serum Level at Study Endpoint [Baseline to 12 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Must have a diagnosis of schizophrenia as confirmed by the MINI

• Must be on antipsychotic medication

• Must be age 50 year or older

• Must be capable of providing written informed consent for study participation. In situations where individuals have guardians of person, guardian and subject must both provide written consent; and

• Must live in the Northeast Ohio area.

Exclusion Criteria:

• A primary psychiatric DSM Axis I diagnosis other than schizophrenia

• Actively abusing substances; or

• Medically unstable.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Hospitals of Cleveland	Cleveland	Ohio	United States	44106

Sponsors and Collaborators

• University Hospitals Cleveland Medical Center
• Abbott

Investigators

• Principal Investigator: Martha Sajatovic, MD, Case Western Reserve University School of Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00194025
• Other Study ID Numbers: 10850-01-L0348
• First Posted: Sep 19, 2005
• Last Update Posted: Jan 6, 2015
• Last Verified: Feb 1, 2011

• Keywords provided by , ,: Schizophrenia; Anticonvulsants; Valproic Acid; Valproate
• Additional relevant MeSH terms: Schizophrenia; Valproic Acid

Study Results

Participant Flow

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.

Arm/Group Title	Valproate
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
COMPLETED	15
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	Valproate
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 Participants	20
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	15 75%
>=65 years	5 25%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.1 (9.6)
Sex: Female, Male (Count of Participants)
Female	16 80%
Male	4 20%
Region of Enrollment (participants) [Number]
United States	20 100%

Outcome Measures

1. Primary Outcome

Title	Change in Schizophrenia Psychopathology as Assessed by the Positive and Negative Symptom Scale (PANSS)
Description	The best and worst possible overall PANSS scores are 30 and 210 units on a scale, respectively.
Time Frame	Baseline to 12 weeks

Outcome Measure Data

Analysis Population Description

Last Observation Carried Forward (LOCF) was used as the imputation technique.

Arm/Group Title	Valproate
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.
Measure Participants	20
Mean (Standard Deviation) [scores on a scale]	-17.45 (14.87)

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
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	t-test, 1 sided
	Comments

2. Secondary Outcome

Title	Change in Cognitive Status as Measured by the Mini-mental State Examination (MMSE)
Description	The best and worst possible overall scores are 31 and 0 units on a scale, respectively.
Time Frame	Baseline to 12 weeks

Outcome Measure Data

Analysis Population Description

Last Observation Carried Forward (LOCF) was used as the imputation technique.

Arm/Group Title	Valproate
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.
Measure Participants	20
Mean (Standard Deviation) [scores on a scale]	0.4 (3.218)

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
Statistical Test of Hypothesis	p-Value	0.585
	Comments
	Method	t-test, 1 sided
	Comments

3. Secondary Outcome

Title	Change in Overall Functioning as Measured by the Global Assessment Scale (GAS)
Description	The best and worst possible GAS scores are 100 and 1 units on a scale, respectively.
Time Frame	Baseline to 12 weeks

Outcome Measure Data

Analysis Population Description

Last Observation Carried Forward (LOCF) was used as the imputation technique.

Arm/Group Title	Valproate
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.
Measure Participants	20
Mean (Standard Deviation) [scores on a scale]	16.35 (15.09)

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
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	t-test, 1 sided
	Comments

4. Secondary Outcome

Title	Change in Depression Symptoms as Measured by the Geriatric Depression Scale (GDS)
Description	The best and worst possible GDS scores are 0 and 30 units on a scale, respectively.
Time Frame	Baseline to 12 weeks

Outcome Measure Data

Analysis Population Description

Last Observation Carried Forward (LOCF) was used as the imputation technique.

Arm/Group Title	Valproate
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.
Measure Participants	18
Mean (Standard Deviation) [scores on a scale]	-1.556 (2.502)

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
Statistical Test of Hypothesis	p-Value	0.017
	Comments
	Method	t-test, 1 sided
	Comments

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)
Description	The best and worst possible MCS scores are 100 and 1 units on a scale, respectively.
Time Frame	Baseline to 12 weeks

Outcome Measure Data

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
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.
Measure Participants	14
Mean (Standard Deviation) [scores on a scale]	5.298 (7.968)

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
Statistical Test of Hypothesis	p-Value	0.027
	Comments
	Method	t-test, 1 sided
	Comments

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)
Description	The best and worst possible PCS scores are 100 and 0 units on a scale, respectively.
Time Frame	Baseline to 12 weeks

Outcome Measure Data

Analysis Population Description

Last Observation Carried Forward (LOCF) was used as the imputation technique.

Arm/Group Title	Valproate
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.
Measure Participants	14
Mean (Standard Deviation) [scores on a scale]	0.932 (5.971)

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
Statistical Test of Hypothesis	p-Value	0.569
	Comments
	Method	t-test, 1 sided
	Comments

7. Secondary Outcome

Title	Change in Extrapyramidal Symptoms as Assessed by the Abnormal Involuntary Movement Scale (AIMS)
Description	The best and worst possible overall scores are 0 and 28 units on a scale, respectively.
Time Frame	Baseline to 12 weeks

Outcome Measure Data

Analysis Population Description

Last Observation Carried Forward (LOCF) was used as the imputation technique.

Arm/Group Title	Valproate
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.
Measure Participants	19
Mean (Standard Deviation) [scores on a scale]	-2.105 (4.108)

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
Statistical Test of Hypothesis	p-Value	0.038
	Comments
	Method	t-test, 1 sided
	Comments

8. Secondary Outcome

Title	Change in Extrapyramidal Symptoms as Assessed by the Simpson Angus Neurological Rating Scale (SAS)
Description	The best and worst possible overall scores are 40 and 0 units on a scale, respectively.
Time Frame	Baseline to 12 weeks

Outcome Measure Data

Analysis Population Description

Last Observation Carried Forward (LOCF) was used as the imputation technique.

Arm/Group Title	Valproate
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.
Measure Participants	15
Mean (Standard Deviation) [scores on a scale]	-0.6 (1.724)

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
Statistical Test of Hypothesis	p-Value	0.199
	Comments
	Method	t-test, 1 sided
	Comments

9. Secondary Outcome

Title	Tolerability as Assessed by Weight Change
Time Frame	Baseline to 12 weeks

Outcome Measure Data

Analysis Population Description

All available data was used implementing LOCF.

Arm/Group Title	Valproate
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.
Measure Participants	18
Mean (Standard Deviation) [kilograms]	1.1 (3.6)

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
Statistical Test of Hypothesis	p-Value	0.21
	Comments
	Method	t-test, 2 sided
	Comments

10. Secondary Outcome

Title	Tolerability as Measured by Mean Serum Level at Study Endpoint
Time Frame	Baseline to 12 weeks

Outcome Measure Data

Analysis Population Description

Last Observation Carried Forward (LOCF) was used as the imputation technique.

Arm/Group Title	Valproate
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.
Measure Participants	20
Mean (Standard Deviation) [ug/mL]	40.86 (25.29)

Adverse Events

Arm/Group Title	Valproate
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 (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Valproate
	Affected / at Risk (%)	# Events
Total	0/20 (0%)
Other (Not Including Serious) Adverse Events
	Valproate
	Affected / at Risk (%)	# Events
Total	0/20 (0%)

Limitations/Caveats

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.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.