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

NCT ID: NCT01423396

Last Updated: 2022-05-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 304 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-03-15
• Study Completion Date: 2022-05-31

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%.

Conditions

Alzheimer's Disease; Cardiovascular Risk Factors

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

standard care

Follow up with city doctor with recommendation HAS French guidelines

Group Type: OTHER

standard care

Intervention Type: OTHER

AD patients will be followed with the city doctor and the letter t will be send for remember French HAS guidelines

optimal care of VRF

Monitoring according to the strict recommendations of the HAS French guidelines

Group Type: EXPERIMENTAL

optimal care of VRF

Intervention Type: OTHER

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.

Interventions

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.

Intervention Type: OTHER

standard care

AD patients will be followed with the city doctor and the letter t will be send for remember French HAS guidelines

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Subjects aged 60 or over
• Subjects with Alzheimer's disease, according to the NINCDS/ADRDA diagnostic criteria 71
• MMSE > 18
• Subjects with at least one VRF (whether treated or not): arterial hypertension (defined as SBP/DBP ≥ 140/90 mmHg in at least three different consultations or, for ambulatory measurements, > 130/80 mmHg with a Holter recorder or > 135/85 mmHg with a self-measurement device), type 2 diabetes (defined as a glycaemia value over 1.26 g/l (7 mmol/l) after an 8-hour fast (confirmed on two occasions), dyslipidaemia (defined as an LDL cholesterol level > 1.6 g/l or 1.3 or 1 g/l, depending on the patient's risk level)
• Subjects having agreed to participate in the study (provision of informed consent).
• Subjects accompanied by a person likely to provide information on the patient (during the visit or over the phone).

Exclusion Criteria

• Any other disease that might interfere with the evaluation of cognitive disorders.
• No formal education or a poor understanding of French (interfering with administration of the neuropsychological tests).
• Major physical problems likely to interfere with administration of the tests (poor eyesight, hearing, etc.).
• Non-Alzheimer's dementia (isolated vascular dementia, Lewy body dementia, frontotemporal dementia, etc.)
• Psychotropic drugs likely to modify the patient's non-stabilized cognitive state.
• Patients with a history of cardiovascular events can be included (randomization will be balanced in terms of this criterion).
• Participation in a therapeutic clinical trial during the study period.

• Minimum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ministry of Health, France

OTHER_GOV

Sponsor Role: collaborator

University Hospital, Lille

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Florence PASQUIER, MD

Role: STUDY_DIRECTOR

Univ Lille Nord de France, clinique neurologique, Centre Mémoire de Ressources et de Recherche - CHRU Lille

Marie-Anne MACKOWIAK, MD

Role: PRINCIPAL_INVESTIGATOR

Univ Lille Nord de France, clinique neurologique, Centre Mémoire de Ressources et de Recherche - CHRU Lille

Didier HANNEQUIN, MD

Role: PRINCIPAL_INVESTIGATOR

CHU Rouen

Olivier GODEFROY, MD

Role: PRINCIPAL_INVESTIGATOR

CHU Amiens

Muriel RAINFRAY, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Bordeaux

Locations

Chu Amiens Picardie

Amiens, , France

CH ARRAS

Arras, , France

Centre Hospitalier Bethune Beuvry

Béthune, , France

CH Boulogne

Boulogne-sur-Mer, , France

Ch Calais -

Calais, , France

CH de DENAIN

Denain, , France

CH de DOUAI

Douai, , France

Ch Dunkerque

Dunkirk, , 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 Saint-Philibert, GHICL

Lomme, , France

Hu Paris Centre Site Broca Aphp - Paris

Paris, , France

CH de ROUBAIX

Roubaix, , 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 Tourcoing

Tourcoing, , France

CH Valenciennes

Valenciennes, , France

Countries

France

Other Identifiers

2009-A00269-48

Identifier Type: OTHER

Identifier Source: secondary_id

PHRC 2008/1925

Identifier Type: OTHER

Identifier Source: secondary_id

B90419-40

Identifier Type: OTHER

Identifier Source: secondary_id

2008_28/0914

Identifier Type: -

Identifier Source: org_study_id