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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: September 15, 2014
Last verified: September 2014
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 
Overall Participants Analyzed 
[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) 
[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.
ADCS-ADL [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 56.9  (11.8)   54.9  (13)   55.9  (12.4) 
[1] 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.
CDR-SOB [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 7.1  (2.7)   7.5  (3.1)   7.3  (2.9) 
[1] 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.
CMAI [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 10.9  (8.9)   11.9  (10.4)   11.4  (9.7) 
[1] 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.
NPI [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 2.6  (2.6)   3.1  (2.6)   2.9  (2.6) 
[1] 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 
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 (94.77%)   151/160 (94.38%) 
Eye disorders     
Vision blurred     
# participants affected / at risk   10/153 (6.54%)   8/160 (5.00%) 
# events   11   8 
Gastrointestinal disorders     
Abdominal discomfort     
# participants affected / at risk   16/153 (10.46%)   13/160 (8.13%) 
# events   19   13 
Constipation     
# participants affected / at risk   26/153 (16.99%)   13/160 (8.13%) 
# events   28   16 
Diarrhoea     
# participants affected / at risk   38/153 (24.84%)   19/160 (11.88%) 
# events   45   24 
Dry mouth     
# participants affected / at risk   16/153 (10.46%)   15/160 (9.38%) 
# events   16   15 
Faecal incontinence     
# participants affected / at risk   8/153 (5.23%)   5/160 (3.13%) 
# events   8   5 
Nausea     
# participants affected / at risk   14/153 (9.15%)   10/160 (6.25%) 
# events   16   11 
Vomiting     
# participants affected / at risk   9/153 (5.88%)   7/160 (4.38%) 
# events   10   7 
General disorders     
Asthenia     
# participants affected / at risk   48/153 (31.37%)   35/160 (21.88%) 
# events   52   37 
Chest pain     
# participants affected / at risk   7/153 (4.58%)   8/160 (5.00%) 
# events   9   8 
Oedema peripheral     
# participants affected / at risk   10/153 (6.54%)   7/160 (4.38%) 
# events   12   7 
Infections and infestations     
Bronchitis     
# participants affected / at risk   7/153 (4.58%)   5/160 (3.13%) 
# events   8   6 
Nasopharyngitis     
# participants affected / at risk   11/153 (7.19%)   9/160 (5.63%) 
# events   12   13 
Urinary tract infection     
# participants affected / at risk   15/153 (9.80%)   17/160 (10.63%) 
# events   19   28 
Injury, poisoning and procedural complications     
Fall     
# participants affected / at risk   54/153 (35.29%)   42/160 (26.25%) 
# events   85   86 
Investigations     
Weight decreased     
# participants affected / at risk   11/153 (7.19%)   11/160 (6.88%) 
# events   12   11 
Metabolism and nutrition disorders     
Decreased appetite     
# participants affected / at risk   8/153 (5.23%)   7/160 (4.38%) 
# events   9   8 
Musculoskeletal and connective tissue disorders     
Arthralgia     
# participants affected / at risk   20/153 (13.07%)   12/160 (7.50%) 
# events   21   14 
Back pain     
# participants affected / at risk   21/153 (13.73%)   20/160 (12.50%) 
# events   21   20 
Joint swelling     
# participants affected / at risk   14/153 (9.15%)   10/160 (6.25%) 
# events   15   12 
Muscular weakness     
# participants affected / at risk   28/153 (18.30%)   14/160 (8.75%) 
# events   32   14 
Myalgia     
# participants affected / at risk   11/153 (7.19%)   11/160 (6.88%) 
# events   12   12 
Nervous system disorders     
Disturbance in attention     
# participants affected / at risk   40/153 (26.14%)   39/160 (24.38%) 
# events   40   39 
Dizziness     
# participants affected / at risk   23/153 (15.03%)   30/160 (18.75%) 
# events   25   36 
Gait disturbance     
# participants affected / at risk   51/153 (33.33%)   30/160 (18.75%) 
# events   64   35 
Headache     
# participants affected / at risk   16/153 (10.46%)   13/160 (8.13%) 
# events   19   16 
Tremor     
# participants affected / at risk   44/153 (28.76%)   22/160 (13.75%) 
# events   51   23 
Psychiatric disorders     
Agitation     
# participants affected / at risk   43/153 (28.10%)   54/160 (33.75%) 
# events   50   74 
Anxiety     
# participants affected / at risk   24/153 (15.69%)   38/160 (23.75%) 
# events   29   47 
Apathy     
# participants affected / at risk   9/153 (5.88%)   9/160 (5.63%) 
# events   9   9 
Confusional state     
# participants affected / at risk   76/153 (49.67%)   79/160 (49.38%) 
# events   114   111 
Crying     
# participants affected / at risk   23/153 (15.03%)   22/160 (13.75%) 
# events   27   24 
Delusion     
# participants affected / at risk   10/153 (6.54%)   14/160 (8.75%) 
# events   11   20 
Depressed mood     
# participants affected / at risk   35/153 (22.88%)   23/160 (14.37%) 
# events   37   26 
Depression     
# participants affected / at risk   18/153 (11.76%)   10/160 (6.25%) 
# events   19   11 
Hallucination     
# participants affected / at risk   9/153 (5.88%)   5/160 (3.13%) 
# events   11   5 
Insomnia     
# participants affected / at risk   20/153 (13.07%)   16/160 (10.00%) 
# events   23   18 
Restlessness     
# participants affected / at risk   28/153 (18.30%)   31/160 (19.38%) 
# events   34   39 
Somnolence     
# participants affected / at risk   66/153 (43.14%)   46/160 (28.75%) 
# events   80   51 
Renal and urinary disorders     
Pollakiuria     
# participants affected / at risk   23/153 (15.03%)   17/160 (10.63%) 
# events   25   19 
Urinary incontinence     
# participants affected / at risk   15/153 (9.80%)   15/160 (9.38%) 
# events   18   16 
Respiratory, thoracic and mediastinal disorders     
Cough     
# participants affected / at risk   21/153 (13.73%)   18/160 (11.25%) 
# events   24   22 
Dyspnoea     
# participants affected / at risk   19/153 (12.42%)   9/160 (5.63%) 
# events   20   9 
Skin and subcutaneous tissue disorders     
Hyperhidrosis     
# participants affected / at risk   4/153 (2.61%)   9/160 (5.63%) 
# events   4   9 
Rash     
# 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