Valproate in Dementia (VALID)

This study has been completed.

Study NCT00071721 Information provided by Alzheimer's Disease Cooperative Study (ADCS)

First Received on October 29, 2003. Last Updated on January 18, 2012 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
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Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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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

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

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 behavorial changes in dementia, including depression, anxiety, psychosis, agitation, sleep change, appetite change, and others. This is a structured questionnaire adminstered 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 ]

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2. Secondary:

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

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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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4. Secondary:

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

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5. Secondary:

Agitation Measured by the Cohen-Mansfield Agitation Inventory (CMAI), Community Version [ Time Frame: 24 months ]

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6. Secondary:

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

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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
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Results Point of Contact:

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

Publications:

Tariot PN, Loy R, Ryan JM, Porsteinsson A, Ismail S. Mood stabilizers in Alzheimer's disease: symptomatic and neuroprotective rationales. Adv Drug Deliv Rev. 2002 Dec 7;54(12):1567-77. Review.

Manji HK, Moore GJ, Rajkowska G, Chen G. Neuroplasticity and cellular resilience in mood disorders. Mol Psychiatry. 2000 Nov;5(6):578-93. Review.

Chen G, Huang LD, Jiang YM, Manji HK. The mood-stabilizing agent valproate inhibits the activity of glycogen synthase kinase-3. J Neurochem. 1999 Mar;72(3):1327-30.

Publications automatically indexed to this study:

Tariot PN, Schneider LS, Cummings J, Thomas RG, Raman R, Jakimovich LJ, Loy R, Bartocci B, Fleisher A, Ismail MS, Porsteinsson A, Weiner M, Jack CR Jr, Thal L, Aisen PS; Alzheimer's Disease Cooperative Study Group. Chronic divalproex sodium to attenuate agitation and clinical progression of Alzheimer disease. Arch Gen Psychiatry. 2011 Aug;68(8):853-61.

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 18, 2012
Health Authority:	United States: Food and Drug Administration