Impact of Controlling Vascular Risk Factors on the Progression of Alzheimer's Disease

Not Applicable

Completed

• Conditions: Cardiovascular Risk Factors; Alzheimer's Disease
• Interventions: Other: standard care; Other: optimal care of VRF

• Registration Number: NCT01423396
• Lead Sponsor: University Hospital, Lille

Brief Summary

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.

Detailed Description

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%.

Study Timeline

• Study Start: 2010-03-15
• Study First Submitted: 2011-08-23
• Study First Submitted QC: 2011-08-23
• Study First Posted: 2011-08-25
• Status Verified: 2022-05
• Primary Completion: 2022-05
• Study Completion: 2022-05
• Last Update Submitted: 2022-05-23
• Last Update Posted: 2022-05-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 304

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
standard care	standard care	Follow up with city doctor with recommendation HAS French guidelines
optimal care of VRF	optimal care of VRF	Monitoring according to the strict recommendations of the HAS French guidelines

Primary Outcome Measures

Name	Time	Method
ADAS-Cog	18 months

Secondary Outcome Measures

Name	Time	Method
NPI	18 months
VADAS-Cog	18 months
MADRS	18 months
MMSE	18 months
Zarit Inventory of Burden	18 months
MoCA	18 months
Trail Making Test	18 months
IADL	18 months
ADL-ADCS	18 months

Trial Locations

Locations (21)

Ch Dunkerque; 🇫🇷 Dunkerque, France

CH Saint-Philibert, GHICL; 🇫🇷 Lomme, France

Ch Tourcoing; 🇫🇷 Tourcoing, France

CH ARRAS; 🇫🇷 Arras, France

Chu Amiens Picardie; 🇫🇷 Amiens, France

CH Boulogne; 🇫🇷 Boulogne-sur-Mer, France

Centre Hospitalier Bethune Beuvry; 🇫🇷 Béthune, France

Ch Calais -; 🇫🇷 Calais, France

CH de DENAIN; 🇫🇷 Denain, France

CH de DOUAI; 🇫🇷 Douai, France

Ch Le Quesnoy; 🇫🇷 Le Quesnoy, France

Ch Dr.Schaffner de Lens; 🇫🇷 Lens, France

CMRR Lille hopital Roger Salengro; 🇫🇷 Lille, France

Hôpital des Bâteliers, CHU; 🇫🇷 Lille, France

CH de ROUBAIX; 🇫🇷 Roubaix, France

Hu Paris Centre Site Broca Aphp - Paris; 🇫🇷 Paris, France

Chu Rouen; 🇫🇷 Rouen, France

Ch Region de St-Omer; 🇫🇷 Saint-Omer, France

Groupe Hospitalier Seclin Carvin -; 🇫🇷 Seclin, France

Chu de Bordeaux - Talence; 🇫🇷 Talence, France

CH Valenciennes; 🇫🇷 Valenciennes, France