Contact information
Type
Scientific
Primary contact
Prof Charles McCollum
ORCID ID
Contact details
Academic Surgery Unit
2nd Floor
Education and Research Centre
University Hospital of South Manchester
Southmoor Road
Manchester
M23 9LT
United Kingdom
+44 (0)161 291 5853
cnmcc@manchester.ac.uk
Additional identifiers
EudraCT number
2005-004283-23
ClinicalTrials.gov number
Protocol/serial number
Protocol version 1, EudraCT number: 2005-004283-23
Study information
Scientific title
An evaluation of potential therapies to inhibit cerebral emboli in dementia
Acronym
Study hypothesis
The causes of common dementias such as Alzheimers Disease (AD) and Vascular Dementia (VAD), which affect 800,000 people in the UK, remain uncertain. We recently found that both AD and VAD are associated with small particles (emboli) in the circulation to the brain and that patients with these emboli suffer a more rapid progression of dementia. Prior to major clinical trials on whether therapy to inhibit emboli may prevent or treat dementia, we need to study possible therapies that may inhibit these emboli. We plan to compare two therapeutic approaches:
1. Platelet inhibition
2. An anti-inflammatory lipid therapy thought to stabilise arterial disease
Patients will be given no new treatments. The number of emboli in the cerebral circulation measured by non-invasive ultrasound, assessment of brain function and markers of inflammation associated with dementia will be measured before and after 1 month of the trial treatment. Any treatment or combination of treatments that inhibit cerebral emboli will then be investigated further in major clinical trials on the treatment of established dementia or the prevention of dementia in at risk elderly people.
Ethics approval
South Manchester Research Ethics Committee, ref: 05/Q1403/214, Amendment number 1 (06/03/2006)
Study design
Randomised controlled clinical trial
Primary study design
Interventional
Secondary study design
Randomised cross over trial
Trial setting
Not specified
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Condition
Dementia, Alzheimer's disease and Vascular Dementia
Intervention
Randomised controlled clinical trial of atorvastatin/clopidogrel/no treatment over 1 month with crossover in 45 patients with Alzheimer's dementia (AD) and 45 with vascular dementia (VaD)
Patients who are already taking aspirin will continue aspirin therapy. No patient will have therapeutic medication withdrawn.
Those with Spontaneous Cerebral Emboli (SCE) will be randomised, stratified for type of dementia, into one of three counterbalanced treatment orders:
1. Clopidogrel; Atorvastatin; No treatment
2. Atorvastatin; No treatment; Clopidogrel
3. No treatment; Clopidogrel; Atorvastatin
Each treatment will last for 1 month, and there is a washout period of 1 week between each treatment. Transcranial Doppler (TCD) measurement of SCE over two separate 1-hour periods on different days in the same week will be repeated after 4 weeks on each therapy.
Intervention type
Drug
Phase
Not Applicable
Drug names
Atorvastatin, clopidogrel
Primary outcome measures
The number of SCE counted during two separate 1-hour periods of monitoring by TCD (at baseline and following each therapy)
Secondary outcome measures
1. Any change in the inflammatory markers to Interleukin-6 or C-Reactive Protein as a result of 1 month therapy with the trial medications
2. Any change in the measures of cognitive function as a result of 1 month of therapy using the trial medications
Overall trial start date
01/07/2007
Overall trial end date
30/06/2009
Reason abandoned
Eligibility
Participant inclusion criteria
1. Dementia: patients must fulfil DSM IV criteria for dementia (Diagnostic and Statistic Manual of Mental Disorders - fourth edition)
2. AD: patients must fulfil the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria
3. VAD: patients must fulfil the National Institute for Neurological and Communicative Disorders and Stroke -Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINCDS−AIREN) criteria
Participant type
Patient
Age group
Senior
Gender
Both
Target number of participants
90 (45 patients with AD and 45 with VaD)
Participant exclusion criteria
1. Patients with a Mini-Mental State Examination (MMSE) score of less than 10 and/or severe aphasia (as the study requires considerable co-operation)
2. Current anticoagulant treatment (may reduce spontaneous emboli)
3. Current clopidogrel treatment
4. Current statin treatment
5. Diagnosed as suffering from Atrial Fibrillation (AF)
6. Diagnosed with significant liver disease: a liver function test will be carried out if liver disease is clinically indicated in any participants
7. Diagnosed with active pathological bleeding such as peptic ulcer or intracranial haemorrhage
8. Any surgery scheduled during study involvement
9. Baseline coagulation parameters suggest unsuitability for clopidogrel/atorvastatin treatment
Recruitment start date
01/07/2007
Recruitment end date
30/06/2009
Locations
Countries of recruitment
United Kingdom
Trial participating centre
University Hospital of South Manchester
Manchester
M23 9LT
United Kingdom
Sponsor information
Organisation
University Hospital of South Manchester (UK)
Sponsor details
c/o Dr Andrew Maines
Research and Development Directorate
Ground Floor
Education and Research Centre
University Hospital of South Manchester
Southmoor Road
Manchester
M23 9LT
United Kingdom
+44 (0)161 291 5775
andrew.maines@manchester.ac.uk
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Charity
Funder name
Alzheimer's Society (UK) (grant ref: 87 [30 January 2007])
Alternative name(s)
Funding Body Type
private sector organisation
Funding Body Subtype
professional associations and societies
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary