Valproate in Dementia (VALID)

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Alzheimer's Disease Cooperative Study (ADCS)
ClinicalTrials.gov Identifier:
NCT00071721
First received: October 29, 2003
Last updated: June 20, 2013
Last verified: June 2013
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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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
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 ]

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

3.  Secondary:   Functional Performance Assessed by the Alzheimer’s Disease Cooperative Study Activities of Daily Living (ADCS-ADL) Inventory   [ Time Frame: 24 months ]

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

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

Measure Type Secondary
Measure Title Agitation Measured by the Cohen-Mansfield Agitation Inventory (CMAI), Community Version
Measure Description 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.
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  
Agitation Measured by the Cohen-Mansfield Agitation Inventory (CMAI), Community Version  
[units: Units on a scale]
Mean ± Standard Deviation
  10.6  ± 11.6     12.1  ± 10.9  

No statistical analysis provided for Agitation Measured by the Cohen-Mansfield Agitation Inventory (CMAI), Community Version



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


  Serious Adverse Events


  Other Adverse Events
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Time Frame No text entered.
Additional Description No text entered.

Frequency Threshold
Threshold above which other adverse events are reported   5%  

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

Other Adverse Events
    Valproate     Placebo  
Total, other (not including serious) adverse events      
# participants affected / at risk     145/153     151/160  
Eye disorders      
Vision blurred 1    
# participants affected / at risk     10/153 (6.54%)     8/160 (5.00%)  
# events     11     8  
Gastrointestinal disorders      
Abdominal discomfort 1    
# participants affected / at risk     16/153 (10.46%)     13/160 (8.13%)  
# events     19     13  
Constipation 1    
# participants affected / at risk     26/153 (16.99%)     13/160 (8.13%)  
# events     28     16  
Diarrhoea 1    
# participants affected / at risk     38/153 (24.84%)     19/160 (11.88%)  
# events     45     24  
Dry mouth 1    
# participants affected / at risk     16/153 (10.46%)     15/160 (9.38%)  
# events     16     15  
Faecal incontinence 1    
# participants affected / at risk     8/153 (5.23%)     5/160 (3.13%)  
# events     8     5  
Nausea 1    
# participants affected / at risk     14/153 (9.15%)     10/160 (6.25%)  
# events     16     11  
Vomiting 1    
# participants affected / at risk     9/153 (5.88%)     7/160 (4.38%)  
# events     10     7  
General disorders      
Asthenia 1    
# participants affected / at risk     48/153 (31.37%)     35/160 (21.88%)  
# events     52     37  
Chest pain 1    
# participants affected / at risk     7/153 (4.58%)     8/160 (5.00%)  
# events     9     8  
Oedema peripheral 1    
# participants affected / at risk     10/153 (6.54%)     7/160 (4.38%)  
# events     12     7  
Infections and infestations      
Bronchitis 1    
# participants affected / at risk     7/153 (4.58%)     5/160 (3.13%)  
# events     8     6  
Nasopharyngitis 1    
# participants affected / at risk     11/153 (7.19%)     9/160 (5.63%)  
# events     12     13  
Urinary tract infection 1    
# participants affected / at risk     15/153 (9.80%)     17/160 (10.63%)  
# events     19     28  
Injury, poisoning and procedural complications      
Fall 1    
# participants affected / at risk     54/153 (35.29%)     42/160 (26.25%)  
# events     85     86  
Investigations      
Weight decreased 1    
# participants affected / at risk     11/153 (7.19%)     11/160 (6.88%)  
# events     12     11  
Metabolism and nutrition disorders      
Decreased appetite 1    
# participants affected / at risk     8/153 (5.23%)     7/160 (4.38%)  
# events     9     8  
Musculoskeletal and connective tissue disorders      
Arthralgia 1    
# participants affected / at risk     20/153 (13.07%)     12/160 (7.50%)  
# events     21     14  
Back pain 1    
# participants affected / at risk     21/153 (13.73%)     20/160 (12.50%)  
# events     21     20  
Joint swelling 1    
# participants affected / at risk     14/153 (9.15%)     10/160 (6.25%)  
# events     15     12  
Muscular weakness 1    
# participants affected / at risk     28/153 (18.30%)     14/160 (8.75%)  
# events     32     14  
Myalgia 1    
# participants affected / at risk     11/153 (7.19%)     11/160 (6.88%)  
# events     12     12  
Nervous system disorders      
Disturbance in attention 1    
# participants affected / at risk     40/153 (26.14%)     39/160 (24.38%)  
# events     40     39  
Dizziness 1    
# participants affected / at risk     23/153 (15.03%)     30/160 (18.75%)  
# events     25     36  
Gait disturbance 1    
# participants affected / at risk     51/153 (33.33%)     30/160 (18.75%)  
# events     64     35  
Headache 1    
# participants affected / at risk     16/153 (10.46%)     13/160 (8.13%)  
# events     19     16  
Tremor 1    
# participants affected / at risk     44/153 (28.76%)     22/160 (13.75%)  
# events     51     23  
Psychiatric disorders      
Agitation 1    
# participants affected / at risk     43/153 (28.10%)     54/160 (33.75%)  
# events     50     74  
Anxiety 1    
# participants affected / at risk     24/153 (15.69%)     38/160 (23.75%)  
# events     29     47  
Apathy 1    
# participants affected / at risk     9/153 (5.88%)     9/160 (5.63%)  
# events     9     9  
Confusional state 1    
# participants affected / at risk     76/153 (49.67%)     79/160 (49.38%)  
# events     114     111  
Crying 1    
# participants affected / at risk     23/153 (15.03%)     22/160 (13.75%)  
# events     27     24  
Delusion 1    
# participants affected / at risk     10/153 (6.54%)     14/160 (8.75%)  
# events     11     20  
Depressed mood 1    
# participants affected / at risk     35/153 (22.88%)     23/160 (14.38%)  
# events     37     26  
Depression 1    
# participants affected / at risk     18/153 (11.76%)     10/160 (6.25%)  
# events     19     11  
Hallucination 1    
# participants affected / at risk     9/153 (5.88%)     5/160 (3.13%)  
# events     11     5  
Insomnia 1    
# participants affected / at risk     20/153 (13.07%)     16/160 (10.00%)  
# events     23     18  
Restlessness 1    
# participants affected / at risk     28/153 (18.30%)     31/160 (19.38%)  
# events     34     39  
Somnolence 1    
# participants affected / at risk     66/153 (43.14%)     46/160 (28.75%)  
# events     80     51  
Renal and urinary disorders      
Pollakiuria 1    
# participants affected / at risk     23/153 (15.03%)     17/160 (10.63%)  
# events     25     19  
Urinary incontinence 1    
# participants affected / at risk     15/153 (9.80%)     15/160 (9.38%)  
# events     18     16  
Respiratory, thoracic and mediastinal disorders      
Cough 1    
# participants affected / at risk     21/153 (13.73%)     18/160 (11.25%)  
# events     24     22  
Dyspnoea 1    
# participants affected / at risk     19/153 (12.42%)     9/160 (5.63%)  
# events     20     9  
Skin and subcutaneous tissue disorders      
Hyperhidrosis 1    
# participants affected / at risk     4/153 (2.61%)     9/160 (5.63%)  
# events     4     9  
Rash 1    
# participants affected / at risk     7/153 (4.58%)     15/160 (9.38%)  
# events     7     17  
1 Term from vocabulary, MedDRA (8.0)



  Limitations and Caveats
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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
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  More Information