An evaluation of potential therapies to inhibit cerebral emboli in dementia

ISRCTN	ISRCTN43384456
DOI	https://doi.org/10.1186/ISRCTN43384456
EudraCT/CTIS number	2005-004283-23
Secondary identifying numbers	Protocol version 1, EudraCT number: 2005-004283-23

Submission date: 05/06/2007
Registration date: 06/07/2007
Last edited: 23/06/2020

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Mental and Behavioural Disorders

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Charles McCollum
Scientific

Academic Surgery Unit
2nd Floor, Education and Research Centre
University Hospital of South Manchester
Southmoor Road
Manchester
M23 9LT
United Kingdom

Phone	+44 (0)161 291 5853
Email	cnmcc@manchester.ac.uk

Study information

Study design	Randomised controlled clinical trial
Primary study design	Interventional
Secondary study design	Randomised cross over trial
Study setting(s)	Not specified
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details to request a patient information sheet
Scientific title	An evaluation of potential therapies to inhibit cerebral emboli in dementia
Study objectives	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(s)	South Manchester Research Ethics Committee, ref: 05/Q1403/214, Amendment number 1 (06/03/2006)
Health condition(s) or problem(s) studied	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
Pharmaceutical study type(s)
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Atorvastatin, clopidogrel
Primary outcome measure	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 study start date	01/07/2007
Completion date	30/06/2009

Eligibility

Participant type(s)	Patient
Age group	Senior
Sex	Both
Target number of participants	90 (45 patients with AD and 45 with VaD)
Total final enrolment	33
Key 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
Key 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
Date of first enrolment	01/07/2007
Date of final enrolment	30/06/2009

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

University Hospital of South Manchester

Manchester
M23 9LT
United Kingdom

Sponsor information

University Hospital of South Manchester (UK)
Hospital/treatment centre

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
England
United Kingdom

Phone	+44 (0)161 291 5775
Email	andrew.maines@manchester.ac.uk
Website	http://www.researchdirectorate.org.uk/
"ROR"	https://ror.org/00he80998

Funders

Funder type

Charity

Alzheimer's Society (UK) (grant ref: 87 [30 January 2007])
Private sector organisation / Associations and societies (private and public)

Alternative name(s): alzheimerssoc
Location: United Kingdom

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Basic results			23/06/2020	No	No

Editorial Notes

23/06/2020: The following changes were made to the trial record:
1. Added clinicaltrialsregister.eu link to basic results (scientific).
2. The total final enrollment was added.
21/03/2017: No publications found, verifying study status with principal investigator.