Clinical trial NCT00142324: CALM-AD
Official title: A Randomised Placebo Controlled Trial of a Cholinesterase Inhibitor in the Management of Agitation in Dementia That is Unresponsive to a Psychological Intervention
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Alzheimer's Disease
Keywords: Dementia
Lead sponsor: Institute of Psychiatry, London
Sponsor class: OTHER
Collaborators: name: Medical Research Council
name: Alzheimer's Society
First posted: 2005-09-02
Enrollment: 190
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: Primary Aim

To determine whether;

* Donepezil is significantly better than placebo in the management of agitation in Alzheimer's Disease that has not responded to, or is inappropriate for a standardised brief psychosocial treatment

Secondary Aims

To determine whether;

* Donepezil has a significant positive or negative impact upon quality of life compared with placebo
* whether there is a significant difference between Donepezil and placebo with respect to cognitive performance
* the cost effectiveness of the pharmacological treatment for agitation


Eligibility criteria: Inclusion Criteria: a diagnosis of dementia consistent with Diagnostic and Statistical Manual of Mental Health Disorders, revised 3rd edition (DSM-III-R) (APA, 1987) National Institute of Neurological and Communicative Disorders and Stroke - Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) diagnostic criteria for probably or possible AD (MKhann et al, 1984) (Appendix 6) clinically significant agitation (defined as causing distress to patient and at least moderate management problems for carers on at least two days per week for a two week period, together with a Cohen Mansfield Agitation Inventory (CMAI) (Cohen-Mansfield, 1986) (Appendix 11 A) score \>39 age \>39 years resident in care facility or community living with a carer not receiving treatment with neuroleptics or cholinesterase inhibitors currently or in the past four weeks and responsible clinician not considering treatment with cholinesterase inhibitor for the next 16 weeks taking into account the clinical evidence base and NICE guideline (NICE, 2001) patient with capacity willing to consent to study or will to participate in study if lacking capacity carer with capacity willing to consent to study and in agreement for patient lacking capacity to participate if patient willing to participate

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Exclusion Criteria:known sensitivity to Donepezil severe, unstable or uncontrolled medical conditions apparent from history, physical examination or investigations current evidence of delirium patient meets criteria for Probably Dementia with Lewy Bodies (McKeith et al, 1996) low probability of treatment compliance

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Primary outcomes:
measure: Cohen Mansfield Agitation Inventory
Secondary outcomes:
measure: Neuropsychiatric Inventory
measure: Standardized Mini-Mental State Examination
measure: Severe Impairment Battery
measure: Clinical Global Impression of Severity/Change
Other outcomes:
Locations:
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Psychiatric Hospital
city: Leicester
country: United Kingdom
facility: Department of Psychiatry for the Elderly, Leicester General Hospital
city: London
country: United Kingdom
facility: Institute of Psychiatry, King's College, London
city: Manchester
country: United Kingdom
facility: Old Age Psychiatry, Wythenshawe Hospital, Manchester
city: Newcastle upon Tyne
country: United Kingdom
facility: Institute for Ageing and Health, Newcastle General Hospital, Newcastle
city: Oxford
country: United Kingdom
facility: Department of Psychiatry, Warneford Hospital, Oxford
city: Southampton
country: United Kingdom
facility: MARC, Moorgreen Hospital, Southamptom
city: Swindon
country: United Kingdom
facility: Department of Old Age Psychiatry, Victoria Hospital, Swindon
Study officials:
affiliation: Institute of Psychiatry, London
name: Robert Howard
role: PRINCIPAL_INVESTIGATOR
affiliation: Queen Elizabeth Psychiatric Hospital, Birmingham
name: Peter Bentham
role: PRINCIPAL_INVESTIGATOR
affiliation: Institute of Psychiatry, London
name: Richard Brown
role: PRINCIPAL_INVESTIGATOR
affiliation: Kingshill Research Centre, Victoria Hospital, Swindon
name: Roger Bullock
role: PRINCIPAL_INVESTIGATOR
affiliation: Wythenshawe Hospital, Manchester
name: Alistair Burns
role: PRINCIPAL_INVESTIGATOR
affiliation: Moorgreen Hospital, Southampton
name: Clive Holmes
role: PRINCIPAL_INVESTIGATOR
affiliation: Warneford Hospital, Oxford
name: Robin Jacoby
role: PRINCIPAL_INVESTIGATOR
affiliation: Leicester General Hospital, Leicester
name: James Lindesay
role: PRINCIPAL_INVESTIGATOR
affiliation: Newcastle General Hospital, Newcastle
name: John O'Brien
role: PRINCIPAL_INVESTIGATOR
References:
citation: Howard RJ, Juszczak E, Ballard CG, Bentham P, Brown RG, Bullock R, Burns AS, Holmes C, Jacoby R, Johnson T, Knapp M, Lindesay J, O'Brien JT, Wilcock G, Katona C, Jones RW, DeCesare J, Rodger M; CALM-AD Trial Group. Donepezil for the treatment of agitation in Alzheimer's disease. N Engl J Med. 2007 Oct 4;357(14):1382-92. doi: 10.1056/NEJMoa066583.