Impact of Controlling Vascular Risk Factors on the Progression of Alzheimer's Disease (COVARAD)
Recruitment status was Recruiting
Three quarters of patients with Alzheimer's disease have at least one vascular risk factor (VRF). Vascular brain lesions are present in most Alzheimer's patients (especially older ones). This cerebrovascular disease potentiates Alzheimer's lesions in early-stage disease. Many research studies have shown that VRFs are also risk factors for Alzheimer's disease; this is true for arterial hypertension and dyslipidaemia in particular and, to a lesser extent, diabetes and cardiopathy. Moreover, recent drug trials (SYST-EUR, PROGRESS and HOPE) have indicated that antihypertensive medications can prevent the appearance of dementia (and notably Alzheimer's disease) in over-60 hypertensive subjects. An observational study of 233 Alzheimer's patients with an average follow-up period of 4 years has shown that the annual decline in the Mini-Mental State Examination (MMSE) score was lower in patients in whom all the VRFs were being treated than in patients in whom no VRFs were being treated (1.5 ± 2.5 points versus 2.5 ± 2 points, respectively; p<0.04).1 However, it is not currently known whether optimal treatment of VRFs can influence the progression and prognosis of Alzheimer's disease. Answering this question could have a significant impact on public health.
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
|Official Title:||Impact of Controlling Vascular Risk Factors on the Progression of Alzheimer's Disease|
- ADAS-Cog [ Time Frame: 18 months ] [ Designated as safety issue: No ]
- MMSE [ Time Frame: 18 months ] [ Designated as safety issue: No ]
- MoCA [ Time Frame: 18 months ] [ Designated as safety issue: No ]
- VADAS-Cog [ Time Frame: 18 months ] [ Designated as safety issue: No ]
- Trail Making Test [ Time Frame: 18 months ] [ Designated as safety issue: No ]
- ADL-ADCS [ Time Frame: 18 months ] [ Designated as safety issue: No ]
- IADL [ Time Frame: 18 months ] [ Designated as safety issue: No ]
- MADRS [ Time Frame: 18 months ] [ Designated as safety issue: No ]
- NPI [ Time Frame: 18 months ] [ Designated as safety issue: No ]
- Zarit Inventory of Burden [ Time Frame: 18 months ] [ Designated as safety issue: No ]
|Study Start Date:||January 2010|
|Estimated Study Completion Date:||January 2014|
|Estimated Primary Completion Date:||January 2013 (Final data collection date for primary outcome measure)|
|No Intervention: standard care|
|Experimental: optimal care||
Other: optimal care of VRF
VRF of AD patients will be treated optimally in strict compliance with the French HAS guidelines concerning targets for blood pressure, glycaemia and blood lipid levels, in accordance with standardized therapeutic regimens.
It is not currently known whether the optimum treatment of VRFs influences the progression and prognosis of Alzheimer's disease. Our starting hypothesis is that VRF control in Alzheimer's patients is associated with slower cognitive decline, less intense loss of personnel independence and fewer adverse events over the course of the disease (cardiovascular or cerebrovascular events, behavioural disorders, caregiver burden, hospitalization and death).
COVARAD study is a randomized, controlled, multicentre study comparing 2 VRF care strategies in mild-to-moderate (MMSE > 18) Alzheimer's disease patients with at least one VRF. The objective of this work is to evaluate the effect of "optimal" care strategy, in strict compliance with the French HAS guidelines concerning targets for blood pressure, glycaemia and blood lipid levels, on the cognitive function in mild-to-moderate Alzheimer's patients (MMSE score > 18), in comparison with a control group (i.e. receiving standard care from a primary care physician). The study test the hypothesis whereby "optimal" care of the 3 main modifiable VRFs is associated with slower cognitive decline in Alzheimer's disease patients (evaluated on the ADAS-cog score), when compared with standard care and to compare the MMSE, MoCA and VADAS-cog scores, mood and behaviour (MADRS and NPI), loss of independence (ADCS-ADL), the occurrence of cardiovascular or cerebrovascular events, the number and length of hospitalisations, caregiver burden (on the Zarit scale), institutionalization and survival in the two groups (i.e. depending whether VRFs are managed optimally or not).
This study could influence clinical practice. If VRF control does have an influence on the progression of Alzheimer's disease, an information campaign could modify practice and have a significant impact on public health.
An independent Data and Safety Monitoring Board will be set up to monitor the diabetic patients, in view of the risks related to "optimal" care (ACCOR and ADVANCE studies). Nevertheless, the risk of adverse events will be limited by raising the threshold value for glycated haemoglobin to 8%.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01423396
|Contact: Florence PASQUIER, MD PhD||320 44 60 21 ext +firstname.lastname@example.org|
|CMRR Lille hopital Roger Salengro||Recruiting|
|Lille, France, 59037|
|Principal Investigator: Florence PASQUIER, MD PhD|
|Study Director:||Florence PASQUIER, MD||Univ Lille Nord de France, clinique neurologique, Centre Mémoire de Ressources et de Recherche - CHRU Lille|
|Principal Investigator:||Olivier HANON, MD||Hôpital Broca, AP-HP, CHU Cochin, Paris V - service de gériatrie, CMRR Ile de France|
|Principal Investigator:||Marie-Anne MACKOWIAK, MD||Univ Lille Nord de France, clinique neurologique, Centre Mémoire de Ressources et de Recherche - CHRU Lille|
|Principal Investigator:||Didier HANNEQUIN, MD||CHU Rouen|
|Principal Investigator:||Olivier GODEFROY, MD||CHU Amiens|
|Principal Investigator:||Muriel RAINFRAY, MD||CHU Bordeaux|
|Principal Investigator:||Philippe DEVOS, MD||CH Boulogne|
|Principal Investigator:||Isabelle GIRARD-BUTTAZ, MD||CH Valenciennes|
|Principal Investigator:||Olivier SENECHAL, MD||CH Lens|
|Principal Investigator:||Isabelle LAVENU, MD||CH Béthune|
|Principal Investigator:||Pierre FORZY, MD||CH Roubaix|
|Principal Investigator:||Gauthier CALAIS, MD||CH Saint-Philibert, GHICL|
|Principal Investigator:||François PUISIEUX, MD||Hôpital des Bâteliers, Lille|
|Principal Investigator:||Olivier DEREEPER, MD||CH Calais|
|Principal Investigator:||Karine GARCON, MD||CH Saint-Omer|