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Valproate in Dementia (VALID)

This study has been completed.
Sponsor:
Collaborator:
National Institute on Aging (NIA)
Information provided by (Responsible Party):
Alzheimer's Disease Cooperative Study (ADCS)
ClinicalTrials.gov Identifier:
NCT00071721
First received: October 29, 2003
Last updated: January 10, 2013
Last verified: January 2013
History of Changes
Results First Received: July 6, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Alzheimer Disease
Interventions: Drug: Valproate
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Valproate 250mg tablets beginning with one daily for one week, then two daily for one week, then titrated according to body weight and tolerability to achieve 10-12 mg/kg daily for 2 years, followed by a 2-month washout
Placebo Placebo tablets beginning with one daily and increasing according to weight and perceived tolerability concerns for two years, followed by a 2-month washout

Participant Flow:   Overall Study
    Valproate     Placebo  
STARTED     153     160  
COMPLETED     81     69  
NOT COMPLETED     72     91  



  Baseline Characteristics
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Reporting Groups
  Description
Valproate 250mg tablets beginning with one daily for one week, then two daily for one week, then titrated according to body weight and tolerability to achieve 10-12 mg/kg daily for 2 years, followed by a 2-month washout
Placebo Placebo tablets beginning with one daily and increasing according to weight and perceived tolerability concerns for two years, followed by a 2-month washout
Total Total of all reporting groups

Baseline Measures
    Valproate     Placebo     Total  
Number of Participants  
[units: participants]
 		  153     160     313  
Age  
[units: years]
Mean ± Standard Deviation 		  74.9  ± 8.2     76.6  ± 7.4     75.7  ± 7.8  
Gender  
[units: participants]
 		     
Female     83     101     184  
Male     70     59     129  
Region of Enrollment  
[units: participants]
 		     
United States     153     160     313  
ADAScog [1]
[units: Units on a scale]
Mean ± Standard Deviation 		  29.4  ± 8.9     30.1  ± 9.8     29.8  ± 9.4  
ADCS-ADL [2]
[units: Units on a scale]
Mean ± Standard Deviation 		  56.9  ± 11.8     54.9  ± 13     55.9  ± 12.4  
CDR-SOB [3]
[units: Units on a scale]
Mean ± Standard Deviation 		  7.1  ± 2.7     7.5  ± 3.1     7.3  ± 2.9  
CMAI [4]
[units: Units on a scale]
Mean ± Standard Deviation 		  10.9  ± 8.9     11.9  ± 10.4     11.4  ± 9.7  
NPI [5]
[units: Units on a scale]
Mean ± Standard Deviation 		  2.6  ± 2.6     3.1  ± 2.6     2.9  ± 2.6  
[1] Alzheimer's Disease Assessment Scale, cognitive sub-scale in points per year (ADAS-cog) is a psychometric measure sensitive to change in mild to moderate AD. The range of this instrument is 0 to 70 with higher numbers indicating greater impairment.
[2] Alzheimer's Disease Cooperative Study Activities of Daily Living Score (ADCS-ADL) is a structured questionnaire about activities of daily living, administered to the subject's caregiver/study partner. The range of this instrument is 0 to 78 with lower numbers indicating greater impairment.
[3] Clinical Dementia Rating, Sum of Boxes (CDR-SOB) is a global rating of dementia severity based on the clinician's interpretation of the history and examination. The range of this instrument is 0 to 18 with higher numbers indicating greater impairment.
[4] The Cohen-Mansfield Agitation Inventory (CMAI) is a 29-item caregiver rating questionnaire for the assessment of agitation in older persons. It includes descriptions of 29 agitated behaviors, each rated on a 7-point scale of frequency. The range of this instrument is 29 to 203 with higher numbers indicating greater impairment.
[5] The Neuropsychiatric Inventory (NPI) quantifies behavioral changes in dementia, including depression, anxiety, psychosis, agitation, sleep change, appetite change, and others. This is a structured questionnaire administered to the subject's caregiver/study partner. The range of this instrument is 0 to 120 with higher numbers indicating greater impairment.



  Outcome Measures
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1.  Primary:   Presence of Agitation and/or Psychosis Measured by the Neuropsychiatric Inventory (NPI) Combined With an Assessment of the Clinical Significance of Behavioral Change Rated by the Study Clinician   [ Time Frame: 24 months ]
  Show Outcome Measure 1

2.  Secondary:   Cognitive Performance Assessed by the Alzheimer's Disease Assessment Scale-cognitive Subtest (ADAS-cog)   [ Time Frame: 24 months ]
  Show Outcome Measure 2

3.  Secondary:   Functional Performance Assessed by the Alzheimer’s Disease Cooperative Study Activities of Daily Living (ADCS-ADL) Inventory   [ Time Frame: 24 months ]
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Measure Type Secondary
Measure Title Functional Performance Assessed by the Alzheimer’s Disease Cooperative Study Activities of Daily Living (ADCS-ADL) Inventory
Measure Description Alzheimer's Disease Cooperative Study Activities of Daily Living Score (ADCS-ADL) is a structured questionnaire about activities of daily living, administered to the subject's caregiver/study partner. The range of this instrument is 0 to 78 with lower numbers indicating greater impairment.
Time Frame 24 months  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Valproate 250mg tablets beginning with one daily for one week, then two daily for one week, then titrated according to body weight and tolerability to achieve 10-12 mg/kg daily for 2 years, followed by a 2-month washout
Placebo Placebo tablets beginning with one daily and increasing according to weight and perceived tolerability concerns for two years, followed by a 2-month washout

Measured Values
    Valproate     Placebo  
Number of Participants Analyzed  
[units: participants]
 		  153     160  
Functional Performance Assessed by the Alzheimer’s Disease Cooperative Study Activities of Daily Living (ADCS-ADL) Inventory  
[units: Units on a scale]
Mean ± Standard Deviation 		  35.1  ± 20.3     41.0  ± 14.81  

No statistical analysis provided for Functional Performance Assessed by the Alzheimer’s Disease Cooperative Study Activities of Daily Living (ADCS-ADL) Inventory



4.  Secondary:   Global Severity of Dementia Using the CDR Sum of Boxes   [ Time Frame: 24 months ]
  Show Outcome Measure 4

5.  Secondary:   Agitation Measured by the Cohen-Mansfield Agitation Inventory (CMAI), Community Version   [ Time Frame: 24 months ]
  Show Outcome Measure 5

6.  Secondary:   Participant’s Clinical Condition or Endpoint Assessed With the ADCS-Clinical Global Impression of Change (ADCS-CGIC)   [ Time Frame: 24 months ]
  Hide Outcome Measure 6

Measure Type Secondary
Measure Title Participant’s Clinical Condition or Endpoint Assessed With the ADCS-Clinical Global Impression of Change (ADCS-CGIC)
Measure Description ADCS-Clinical Global Impression of Change (ADCS-CGIC) provides a means to reliably assess global change from baseline. It provides a semi-structured format to allow clinicians to gather necessary clinical information from both the participant and informant, in order to make an overall impression of clinical change. The range of this instrument is 1 to 7 with lower numbers indicating improvement and higher numbers indicating a worsened state.
Time Frame 24 months  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Valproate 250mg tablets beginning with one daily for one week, then two daily for one week, then titrated according to body weight and tolerability to achieve 10-12 mg/kg daily for 2 years, followed by a 2-month washout
Placebo Placebo tablets beginning with one daily and increasing according to weight and perceived tolerability concerns for two years, followed by a 2-month washout

Measured Values
    Valproate     Placebo  
Number of Participants Analyzed  
[units: participants]
 		  153     160  
Participant’s Clinical Condition or Endpoint Assessed With the ADCS-Clinical Global Impression of Change (ADCS-CGIC)  
[units: Units on a scale]
Mean ± Standard Deviation 		  5.7  ± 0.9     5.5  ± 1.1  

No statistical analysis provided for Participant’s Clinical Condition or Endpoint Assessed With the ADCS-Clinical Global Impression of Change (ADCS-CGIC)




  Serious Adverse Events
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  Other Adverse Events
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  More Information
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Certain Agreements:  
Principal Investigators are NOT 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.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: Paul Aisen
Organization: Alzheimer's Disease Cooperative Study
phone: 858-622-2028
e-mail: paisen@ucsd.edu


Publications:

Publications automatically indexed to this study:


Responsible Party: Alzheimer's Disease Cooperative Study (ADCS)
ClinicalTrials.gov Identifier: NCT00071721     History of Changes
Other Study ID Numbers: IA0043, 1RC2AG036535, IND 67,222, ADCS Protocol ADC-022-VN
Study First Received: October 29, 2003
Results First Received: July 6, 2010
Last Updated: January 10, 2013
Health Authority: United States: Food and Drug Administration