Alzheimer's DiseaseCOVARADNCT01423396
Impact of Controlling Vascular Risk Factors on the Progression of Alzheimer's Disease
A study testing optimal care of VRF in people with Alzheimer's Disease and Cardiovascular Risk Factors, run by University Hospital, Lille at 21 sites in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Alzheimer's Disease, Cardiovascular Risk Factors
- What is being tested?
- optimal care of VRF
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 304 participants
- Where
- 21 sitesFrance
- Study dates
- 15 Mar 2010to May 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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.
Trial locations and contacts
21 sites in 1 country.
21 sites in 1 country
France21 sites
Chu Amiens Picardie
Amiens
CH ARRAS
Arras
Centre Hospitalier Bethune Beuvry
Béthune
CH Boulogne
Boulogne-sur-Mer
Ch Calais -
Calais
CH de DENAIN
Denain
CH de DOUAI
Douai
Ch Dunkerque
Dunkirk
Ch Le Quesnoy
Le Quesnoy
Ch Dr.Schaffner de Lens
Lens
CMRR Lille hopital Roger Salengro
Lille, 59037
Hôpital des Bâteliers, CHU
Lille, 59037
CH Saint-Philibert, GHICL
Lomme
Hu Paris Centre Site Broca Aphp - Paris
Paris
CH de ROUBAIX
Roubaix
Chu Rouen
Rouen
Ch Region de St-Omer
Saint-Omer
Groupe Hospitalier Seclin Carvin -
Seclin
Chu de Bordeaux - Talence
Talence, 33404
Ch Tourcoing
Tourcoing
CH Valenciennes
Valenciennes
About this study
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.
Read the 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
- Being tested
- optimal care of VRF, standard care
- Keywords
- Alzheimer's disease, cardiovascular risk factors
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
optimal care of VRFOther
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.
standard careOther
AD patients will be followed with the city doctor and the letter t will be send for remember French HAS guidelines
| Study group | Role | What they receive |
|---|---|---|
| standard care | Other | Follow up with city doctor with recommendation HAS French guidelines Receives: Other: standard care |
| optimal care of VRF | Experimental | Monitoring according to the strict recommendations of the HAS French guidelines Receives: Other: optimal care of VRF |
What is being measured
The primary outcome is the main question the study is designed to answer.
ADAS-Cog
Measured: 18 months
Secondary outcomes (9)
MMSE
Measured: 18 months
MoCA
Measured: 18 months
VADAS-Cog
Measured: 18 months
Trail Making Test
Measured: 18 months
ADL-ADCS
Measured: 18 months
IADL
Measured: 18 months
MADRS
Measured: 18 months
NPI
Measured: 18 months
Zarit Inventory of Burden
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Aug 2011 (estimated)
- Study start15 Mar 2010
- Primary completionMay 2022
- Study completionMay 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer's DiseaseStudies of the same condition, open and under way.
- More trials run by University Hospital, LilleThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 304 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Lille
- Sponsor type
- University, hospital or other
- Collaborators
- Ministry of Health, France
- Responsible party
- Sponsor
- Investigators
- Florence PASQUIER, MD, Study director, Univ Lille Nord de France, clinique neurologique, Centre Mémoire de Ressources et de Recherche - CHRU LilleMarie-Anne MACKOWIAK, MD, Principal investigator, Univ Lille Nord de France, clinique neurologique, Centre Mémoire de Ressources et de Recherche - CHRU LilleDidier HANNEQUIN, MD, Principal investigator, CHU RouenOlivier GODEFROY, MD, Principal investigator, CHU AmiensMuriel RAINFRAY, MD, Principal investigator, University Hospital, Bordeaux
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01423396
- Sponsor's protocol ID
- 2008_28/0914
- Other IDs
- 2009-A00269-48, PHRC 2008/1925, B90419-40
- Acronym
- COVARAD
- Status last verified
- May 2022
- First submitted
- 23 Aug 2011
- Last updated
- 24 May 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Controlling Vascular Risk Factors on the Progression of Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT01423396
- Acronym / sponsor ID
- COVARAD / 2008_28/0914
- Conditions
- Alzheimer's Disease, Cardiovascular Risk Factors
- Keywords
- Alzheimer's disease, cardiovascular risk factors
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 304 participants (actual)
- Lead sponsor
- University Hospital, LilleUniversity, hospital or other
- Collaborators
- Ministry of Health, France
- Study start
- 15 Mar 2010 (actual)
- Primary completion
- May 2022 (actual)
- Study completion
- May 2022 (actual)
- First posted
- 25 Aug 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| standard care | Other | Other: standard careFollow up with city doctor with recommendation HAS French guidelines |
| optimal care of VRF | Experimental | Other: optimal care of VRFMonitoring according to the strict recommendations of the HAS French guidelines |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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).
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| optimal care of VRFVRF 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. | Other | optimal care of VRF |
| standard careAD patients will be followed with the city doctor and the letter t will be send for remember French HAS guidelines | Other | standard care |
Primary outcome
ADAS-Cog
Time frame: 18 months
9 secondary outcomes
MMSE
Time frame: 18 months
MoCA
Time frame: 18 months
VADAS-Cog
Time frame: 18 months
Trail Making Test
Time frame: 18 months
ADL-ADCS
Time frame: 18 months
IADL
Time frame: 18 months
MADRS
Time frame: 18 months
NPI
Time frame: 18 months
Zarit Inventory of Burden
Time frame: 18 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 May 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Florence PASQUIER, MD study director
Univ Lille Nord de France, clinique neurologique, Centre Mémoire de Ressources et de Recherche - CHRU Lille
Marie-Anne MACKOWIAK, MD principal investigator
Univ Lille Nord de France, clinique neurologique, Centre Mémoire de Ressources et de Recherche - CHRU Lille
Didier HANNEQUIN, MD principal investigator
CHU Rouen
21 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing optimal care of VRF in people with Alzheimer's Disease and Cardiovascular Risk Factors, run by University Hospital, Lille at 21 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ADAS-Cog (time frame: 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 May 2022.