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: 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  
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 ]

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
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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

Serious Adverse Events
    Valproate     Placebo  
Total, serious adverse events      
# participants affected / at risk     51/153 (33.33%)     62/160 (38.75%)  
Blood and lymphatic system disorders      
Anaemia 1    
# participants affected / at risk     1/153 (0.65%)     2/160 (1.25%)  
# events     1     2  
Cardiac disorders      
Angina pectoris 1    
# participants affected / at risk     0/153 (0.00%)     1/160 (0.63%)  
# events     0     1  
Angina unstable 1    
# participants affected / at risk     1/153 (0.65%)     0/160 (0.00%)  
# events     1     0  
Atrial fibrillation 1    
# participants affected / at risk     3/153 (1.96%)     1/160 (0.63%)  
# events     4     2  
Bradycardia 1    
# participants affected / at risk     0/153 (0.00%)     1/160 (0.63%)  
# events     0     1  
Cardiac disorder 1    
# participants affected / at risk     1/153 (0.65%)     0/160 (0.00%)  
# events     1     0  
Cardiac failure 1    
# participants affected / at risk     0/153 (0.00%)     1/160 (0.63%)  
# events     0     1  
Cardiac failure congestive 1    
# participants affected / at risk     0/153 (0.00%)     1/160 (0.63%)  
# events     0     2  
Myocardial infarction 1    
# participants affected / at risk     0/153 (0.00%)     1/160 (0.63%)  
# events     0     1  
Sinus tachycardia 1    
# participants affected / at risk     0/153 (0.00%)     1/160 (0.63%)  
# events     0     1  
Endocrine disorders      
Hypothyroidism 1    
# participants affected / at risk     0/153 (0.00%)     1/160 (0.63%)  
# events     0     1  
Gastrointestinal disorders      
Abdominal distension 1    
# participants affected / at risk     1/153 (0.65%)     0/160 (0.00%)  
# events     1     0  
Abdominal pain 1    
# participants affected / at risk     1/153 (0.65%)     0/160 (0.00%)  
# events     1     0  
Dysphagia 1    
# participants affected / at risk     1/153 (0.65%)     0/160 (0.00%)  
# events     1     0  
Faecaloma 1    
# participants affected / at risk     1/153 (0.65%)     0/160 (0.00%)  
# events     1     0  
Femoral hernia 1    
# participants affected / at risk     0/153 (0.00%)     1/160 (0.63%)  
# events     0     1  
Gastric haemorrhage 1    
# participants affected / at risk     1/153 (0.65%)     0/160 (0.00%)  
# events     1     0  
Gastric ulcer haemorrhage 1    
# participants affected / at risk     0/153 (0.00%)     1/160 (0.63%)  
# events     0     1  
Gastrointestinal haemorrhage 1    
# participants affected / at risk     0/153 (0.00%)     2/160 (1.25%)  
# events     0     2  
Oesophageal obstruction 1    
# participants affected / at risk     1/153 (0.65%)     0/160 (0.00%)  
# events     1     0  
Rectal haemorrhage 1    
# participants affected / at risk     0/153 (0.00%)     1/160 (0.63%)  
# events     0     1  
General disorders      
Chest pain 1    
# participants affected / at risk     3/153 (1.96%)     1/160 (0.63%)  
# events     3     1  
Death 1    
# participants affected / at risk     5/153 (3.27%)     7/160 (4.38%)  
# events     5     7  
Pyrexia 1    
# participants affected / at risk     1/153 (0.65%)     0/160 (0.00%)  
# events     1     0  
Hepatobiliary disorders      
Cholecystitis 1    
# participants affected / at risk     0/153 (0.00%)     1/160 (0.63%)  
# events     0     1  
Hepatic mass 1    
# participants affected / at risk     1/153 (0.65%)     0/160 (0.00%)  
# events     1     0  
Infections and infestations      
Bronchitis 1    
# participants affected / at risk     1/153 (0.65%)     0/160 (0.00%)  
# events     1     0  
Cellulitis 1    
# participants affected / at risk     0/153 (0.00%)     1/160 (0.63%)  
# events     0     1  
Enterococcal bacteraemia 1    
# participants affected / at risk     0/153 (0.00%)     1/160 (0.63%)  
# events     0     1  
Infection 1    
# participants affected / at risk     0/153 (0.00%)     2/160 (1.25%)  
# events     0     2  
Influenza 1    
# participants affected / at risk     1/153 (0.65%)     0/160 (0.00%)  
# events     1     0  
Kidney infection 1    
# participants affected / at risk     2/153 (1.31%)     0/160 (0.00%)  
# events     2     0  
Listeriosis 1    
# participants affected / at risk     1/153 (0.65%)     0/160 (0.00%)  
# events     1     0  
Nasopharyngitis 1    
# participants affected / at risk     0/153 (0.00%)     1/160 (0.63%)  
# events     0     1  
Pneumonia 1    
# participants affected / at risk     5/153 (3.27%)     6/160 (3.75%)  
# events     5     6  
Pneumonia bacterial 1    
# participants affected / at risk     0/153 (0.00%)     1/160 (0.63%)  
# events     0     1  
Postoperative infection 1    
# participants affected / at risk     0/153 (0.00%)     1/160 (0.63%)  
# events     0     1  
Urinary tract infection 1    
# participants affected / at risk     4/153 (2.61%)     3/160 (1.88%)  
# events     5     3  
Injury, poisoning and procedural complications      
Accidental overdose 1    
# participants affected / at risk     1/153 (0.65%)     0/160 (0.00%)  
# events     1     0  
Drug toxicity 1    
# participants affected / at risk     1/153 (0.65%)     0/160 (0.00%)  
# events     1     0  
Fall 1    
# participants affected / at risk     6/153 (3.92%)     9/160 (5.63%)  
# events     6     10  
Fractured sacrum 1    
# participants affected / at risk     0/153 (0.00%)     1/160 (0.63%)  
# events     0     1  
Head injury 1    
# participants affected / at risk     1/153 (0.65%)     0/160 (0.00%)  
# events     1     0  
Hip fracture 1    
# participants affected / at risk     0/153 (0.00%)     2/160 (1.25%)  
# events     0     2  
Joint dislocation 1    
# participants affected / at risk     0/153 (0.00%)     1/160 (0.63%)  
# events     0     1  
Subdural haematoma 1    
# participants affected / at risk     1/153 (0.65%)     0/160 (0.00%)  
# events     2     0  
Upper limb fracture 1    
# participants affected / at risk     0/153 (0.00%)     1/160 (0.63%)  
# events     0     1  
Investigations      
Liver function test abnormal 1    
# participants affected / at risk     1/153 (0.65%)     0/160 (0.00%)  
# events     1     0  
Metabolism and nutrition disorders      
Decreased appetite 1    
# participants affected / at risk     0/153 (0.00%)     1/160 (0.63%)  
# events     0     1  
Dehydration 1    
# participants affected / at risk     3/153 (1.96%)     0/160 (0.00%)  
# events     3     0  
Hypoglycaemia 1    
# participants affected / at risk     1/153 (0.65%)     0/160 (0.00%)  
# events     1     0  
Hypokalaemia 1    
# participants affected / at risk     1/153 (0.65%)     0/160 (0.00%)  
# events     1     0  
Musculoskeletal and connective tissue disorders      
Arthralgia 1    
# participants affected / at risk     1/153 (0.65%)     0/160 (0.00%)  
# events     1     0  
Arthritis 1    
# participants affected / at risk     0/153 (0.00%)     1/160 (0.63%)  
# events     0     1  
Chondropathy 1    
# participants affected / at risk     1/153 (0.65%)     0/160 (0.00%)  
# events     1     0  
Muscular weakness 1    
# participants affected / at risk     1/153 (0.65%)     0/160 (0.00%)  
# events     1     0  
Musculoskeletal chest pain 1    
# participants affected / at risk     0/153 (0.00%)     1/160 (0.63%)  
# events     0     1  
Spondylolisthesis 1    
# participants affected / at risk     1/153 (0.65%)     0/160 (0.00%)  
# events     1     0  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)      
Breast cancer 1    
# participants affected / at risk     0/153 (0.00%)     1/160 (0.63%)  
# events     0     1  
Colon cancer 1    
# participants affected / at risk     0/153 (0.00%)     1/160 (0.63%)  
# events     0     1  
Mantle cell lymphoma 1    
# participants affected / at risk     0/153 (0.00%)     1/160 (0.63%)  
# events     0     1  
Metastatic neoplasm 1    
# participants affected / at risk     0/153 (0.00%)     1/160 (0.63%)  
# events     0     1  
Prostate cancer 1    
# participants affected / at risk     1/153 (0.65%)     0/160 (0.00%)  
# events     1     0  
Rectal cancer 1    
# participants affected / at risk     0/153 (0.00%)     1/160 (0.63%)  
# events     0     1  
Nervous system disorders      
Cerebral artery occlusion 1    
# participants affected / at risk     1/153 (0.65%)     0/160 (0.00%)  
# events     1     0  
Cerebral infarction 1    
# participants affected / at risk     0/153 (0.00%)     1/160 (0.63%)  
# events     0     1  
Cerebrovascular accident 1    
# participants affected / at risk     0/153 (0.00%)     1/160 (0.63%)  
# events     0     1  
Convulsion 1    
# participants affected / at risk     0/153 (0.00%)     4/160 (2.50%)  
# events     0     4  
Coordination abnormal 1    
# participants affected / at risk     0/153 (0.00%)     1/160 (0.63%)  
# events     0     1  
Depressed level of consciousness 1    
# participants affected / at risk     1/153 (0.65%)     1/160 (0.63%)  
# events     1     1  
Dizziness 1    
# participants affected / at risk     2/153 (1.31%)     1/160 (0.63%)  
# events     2     1  
Loss of consciousness 1    
# participants affected / at risk     0/153 (0.00%)     1/160 (0.63%)  
# events     0     1  
Lumbar radiculopathy 1    
# participants affected / at risk     0/153 (0.00%)     1/160 (0.63%)  
# events     0     1  
Subdural haematoma 1    
# participants affected / at risk     1/153 (0.65%)     0/160 (0.00%)  
# events     1     0  
Subdural haemorrhage 1    
# participants affected / at risk     1/153 (0.65%)     0/160 (0.00%)  
# events     1     0  
Syncope 1    
# participants affected / at risk     4/153 (2.61%)     2/160 (1.25%)  
# events     4     2  
Transient ischaemic attack 1    
# participants affected / at risk     1/153 (0.65%)     0/160 (0.00%)  
# events     1     0  
Psychiatric disorders      
Abnormal behaviour 1    
# participants affected / at risk     1/153 (0.65%)     0/160 (0.00%)  
# events     1     0  
Agitation 1    
# participants affected / at risk     0/153 (0.00%)     2/160 (1.25%)  
# events     0     2  
Confusional state 1    
# participants affected / at risk     2/153 (1.31%)     0/160 (0.00%)  
# events     2     0  
Delirium 1    
# participants affected / at risk     0/153 (0.00%)     1/160 (0.63%)  
# events     0     1  
Hallucination 1    
# participants affected / at risk     1/153 (0.65%)     0/160 (0.00%)  
# events     1     0  
Lethargy 1    
# participants affected / at risk     0/153 (0.00%)     1/160 (0.63%)  
# events     0     1  
Mental disorder 1    
# participants affected / at risk     0/153 (0.00%)     1/160 (0.63%)  
# events     0     1  
Renal and urinary disorders      
Haematuria 1    
# participants affected / at risk     1/153 (0.65%)     0/160 (0.00%)  
# events     1     0  
Urinary incontinence 1    
# participants affected / at risk     1/153 (0.65%)     0/160 (0.00%)  
# events     1     0  
Urinary retention 1    
# participants affected / at risk     1/153 (0.65%)     1/160 (0.63%)  
# events     1     1  
Reproductive system and breast disorders      
Breast swelling 1    
# participants affected / at risk     1/153 (0.65%)     0/160 (0.00%)  
# events     1     0  
Respiratory, thoracic and mediastinal disorders      
Dyspnoea 1    
# participants affected / at risk     1/153 (0.65%)     3/160 (1.88%)  
# events     1     3  
Pneumonia aspiration 1    
# participants affected / at risk     0/153 (0.00%)     1/160 (0.63%)  
# events     0     1  
Pulmonary embolism 1    
# participants affected / at risk     0/153 (0.00%)     1/160 (0.63%)  
# events     0     1  
Respiratory distress 1    
# participants affected / at risk     0/153 (0.00%)     1/160 (0.63%)  
# events     0     1  
Skin and subcutaneous tissue disorders      
Hyperhidrosis 1    
# participants affected / at risk     0/153 (0.00%)     1/160 (0.63%)  
# events     0     1  
Skin ulcer 1    
# participants affected / at risk     1/153 (0.65%)     0/160 (0.00%)  
# events     1     0  
Surgical and medical procedures      
Bladder repair 1    
# participants affected / at risk     0/153 (0.00%)     1/160 (0.63%)  
# events     0     1  
Breast reconstruction 1    
# participants affected / at risk     0/153 (0.00%)     1/160 (0.63%)  
# events     0     1  
Cardiac pacemaker replacement 1    
# participants affected / at risk     1/153 (0.65%)     0/160 (0.00%)  
# events     1     0  
Cholecystectomy 1    
# participants affected / at risk     1/153 (0.65%)     1/160 (0.63%)  
# events     1     1  
Gallbladder operation 1    
# participants affected / at risk     1/153 (0.65%)     0/160 (0.00%)  
# events     1     0  
Hip arthroplasty 1    
# participants affected / at risk     1/153 (0.65%)     0/160 (0.00%)  
# events     1     0  
Hospitalisation 1    
# participants affected / at risk     0/153 (0.00%)     1/160 (0.63%)  
# events     0     1  
Joint arthroplasty 1    
# participants affected / at risk     0/153 (0.00%)     1/160 (0.63%)  
# events     0     1  
Knee operation 1    
# participants affected / at risk     0/153 (0.00%)     1/160 (0.63%)  
# events     0     1  
Leg amputation 1    
# participants affected / at risk     0/153 (0.00%)     1/160 (0.63%)  
# events     0     1  
Lesion excision 1    
# participants affected / at risk     1/153 (0.65%)     0/160 (0.00%)  
# events     1     0  
Surgery 1    
# participants affected / at risk     1/153 (0.65%)     0/160 (0.00%)  
# events     1     0  
Uterine prolapse repair 1    
# participants affected / at risk     0/153 (0.00%)     1/160 (0.63%)  
# events     0     1  
Ventriculo-peritoneal shunt 1    
# participants affected / at risk     0/153 (0.00%)     1/160 (0.63%)  
# events     0     1  
Whole blood transfusion 1    
# participants affected / at risk     0/153 (0.00%)     1/160 (0.63%)  
# events     0     1  
Vascular disorders      
Deep vein thrombosis 1    
# participants affected / at risk     1/153 (0.65%)     0/160 (0.00%)  
# events     2     0  
Hypertension 1    
# participants affected / at risk     1/153 (0.65%)     1/160 (0.63%)  
# events     1     1  
Hypotension 1    
# participants affected / at risk     0/153 (0.00%)     1/160 (0.63%)  
# events     0     1  
Pulmonary embolism 1    
# participants affected / at risk     0/153 (0.00%)     1/160 (0.63%)  
# events     0     1  
Thrombosis 1    
# participants affected / at risk     0/153 (0.00%)     1/160 (0.63%)  
# events     0     1  
1 Term from vocabulary, MedDRA (8.0)




  Other Adverse Events


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