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

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2014 by University Hospital, Lille
Sponsor:
Collaborator:
Ministry of Health, France
Information provided by (Responsible Party):
University Hospital, Lille
ClinicalTrials.gov Identifier:
NCT01423396
First received: August 23, 2011
Last updated: November 6, 2014
Last verified: November 2014
  Purpose

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.


Condition Intervention
Alzheimer's Disease
Cardiovascular Risk Factors
Other: optimal care of VRF
Other: standard care

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by University Hospital, Lille:

Primary Outcome Measures:
  • ADAS-Cog [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 406
Study Start Date: March 2010
Estimated Study Completion Date: January 2017
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
standard care Other: standard care
AD patients will be followed with the city doctor and the letter t will be send for remember French HAS guidelines
Experimental: optimal care of VRF 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.

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%.

  Eligibility

Ages Eligible for Study:   60 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01423396

Contacts
Contact: Florence PASQUIER, MD PhD 320 44 60 21 ext +33 florence.pasquier@chru-lille.fr

Locations
France
CMRR Lille hopital Roger Salengro Recruiting
Lille, France, 59037
Principal Investigator: Florence PASQUIER, MD PhD         
Sponsors and Collaborators
University Hospital, Lille
Ministry of Health, France
Investigators
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
  More Information

No publications provided

Responsible Party: University Hospital, Lille
ClinicalTrials.gov Identifier: NCT01423396     History of Changes
Other Study ID Numbers: 2008_28/0914, 2009-A00269-48, PHRC 2008/1925, B90419-40
Study First Received: August 23, 2011
Last Updated: November 6, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Lille:
Alzheimer's disease
cardiovascular risk factors

Additional relevant MeSH terms:
Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Dementia
Mental Disorders
Nervous System Diseases
Neurodegenerative Diseases
Tauopathies

ClinicalTrials.gov processed this record on November 20, 2014