Cerebrovascular DisordersPhase 4LEOPOLDNCT02472028
Blood Pressure Reduction to Limit the Evolution of Vascular Brain Lesions in Elderly Individuals
A Phase 4 study testing blood pressure lowering algorithm and usual strategy in people with Cerebrovascular Disorders, run by Assistance Publique - Hôpitaux de Paris at 2 sites in France.
Trial summary
The purpose of the study is to test the hypothesis of slowing the progression of White Matter Lesions (WML) by lowering blood pressure (BP) in patients with cognitive complaints and a moderate to high grade of WML on brain MRI. Read more about this study
- Who is it for?
- Ages 60 to 88 years
- Conditions the study is for
- Cerebrovascular Disorders
- What is being tested?
- blood pressure lowering algorithm and usual strategy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 820 participants
- Where
- 2 sitesFrance
- Study dates
- Sep 2015to 11 Sep 2028
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
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 to 88 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 60 to 88 years old patients;
- Patient with cognitive complaint with MMSE ≥ 20performed within 6 months prior to enrollment (with or without dementia)
- Patient with a socio-educational level ≥ 3
- Presence of hyperintensities of moderate to high grade on the last MRI or old scan (grades C and D on the modified Scheltens scale, grades 2/3 Fazekas).
- Hypertension defined by a Systolic Blood Pressure (SBP) and / or a Diastolic Blood Pressure (DBP) ≥ 140/90 mmHg, treated or not
- Affiliation to a social security system
- Informed consent given, signed consent
Who cannot join
- Presence of severe orthostatic hypotension defined as a decrease of 30 mmHg in SBP standing within 3 minutes
- Contraindication to MRI (presence of ferromagnetic foreign body (especially some intracranial clips, some heart valves, intraocular foreign bodies, metal prosthesis), subject carrying pacemaker, claustrophobic participants)
- Severe diseases associated with a life expectancy of less than 3 months;
- Major physical impairments that can interfere with the feasibility of the tests (sight, hearing ...)
- Presence of another dementia different than Alzheimer's disease vascular dementia or mixed dementia,
- Persons under guardianship;
Show all 10Show fewer
- Secondary hypertension: renovascular hypertension, primary aldosteronism, pheochromocytoma ...;
- Patient already receiving 4 or more antihypertensive drugs at maximum dosage
- Patient participating in another clinical research study on drug requiring exclusion period
- severe renal impairment
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Christophe TZOURIO, MD, PhD contact
France2 sites, 2 recruiting
- Not yet recruiting
Memory for Research and Resources Center / Neuroscience pole
Bordeaux, Pellegrin Hospital Group, 33076
Christophe Tzourio, MD, PhD, +33 (0)5 57 57 16 59, christophe.tzourio@u-bordeaux.fr
Stéphanie DEBETTE, MD, PhD, Tel: +33 (0) 5 57 57 16 59, stephanie.debette@isped.u-bordeaux2.fr
- Recruiting
Memory Resources Centre and South of Ile de France Search - Broca Hospital
Paris, 75013
Olivier HANON, MD, PhD, 33 1 44 08 35 02, olivier.hanon@brc.aphp.fr
Stéphanie DEBETTE, MD, PhD, +33 (0) 5 57 57 16 59, stephanie.debette@isped.u-bordeaux2.fr
About this study
Official title: LEukoaraiosis and blOod Pressure Reduction in OLD People
The purpose of the study is to test the hypothesis of slowing the progression of White Matter Lesions (WML) by lowering blood pressure (BP) in patients with cognitive complaints and a moderate to high grade of WML on brain MRI.
Read the detailed description
SCIENTIFIC BACKGROUND: White Matter Lesions (WML) are cerebrovascular abnormalities discovered on MRI that are associated with an increased risk of dementia. High blood pressure (BP) is a major risk factor for WML. WML are therefore key lesions in the causal chain linking vascular factors and dementia, particularly Alzheimer's disease.
However, it has not been shown that lowering BP could limit the progression of the WML in people with cognitive impairment.
OBJECTIVES: To test the hypothesis of slowing progression of WML by lowering BP in patients with memory complaints with a moderate to high grade of WML on brain MRI.
STUDY DESIGN: PROBE (Prospective randomized open blinded end-point) trial. Blind reading of both MRI for every patient in each group. After stratified randomization on age, sex and center, patients will be assigned to two strategies:
- Reinforced Group (RG): enhanced strategy aiming at a systolic BP <135 mmHg;
- Usual Group (UG): usual strategy based on the usual routine care.
SAMPLE SIZE: patients will be enrolled (410 in each arm) in 12 Memory Resources and Research Center (CMRR) with access to 1.5 T or more MRI.
CONDUCT OF THE STUDY:
Duration of the inclusion period: 96 months and 2 weeks. Patient participation duration: 36 months + 6 months max Total study duration: 11 years. Clinical and para-clinical evaluation: MRI as part of research at the beginning of the study and before the end of the study at 36 months + 6 months max (primary endpoint); Clinical evaluation of neuropsychological tests at the beginning of the study and yearly ; walking speed measurement single leg stance balance test ; repeated BP measurements; monitoring of neurological signs and symptoms; blood test at the beginning of the study (electrolytes, lipid profiles, fasting blood glucose, if not existing); MRI if not existing for validation of the inclusion criterion and performed in the ordinary course.
- Conditions
- Cerebrovascular Disorders
- Being tested
- blood pressure lowering algorithm, usual strategy
- Keywords
- Cerebrovascular Disorders, Stroke, Antihypertensive Agents, Arterial Pressure, Memory Disorders
- Medical subject headings
- Cerebrovascular Disorders, Stroke, Memory Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
blood pressure lowering algorithmOther
Also called enhanced strategy
The treatments used in the "enhanced strategy" arm are those proposed by national (HAS2013, SFHTA2013) and international (ESH 2013) recommendations, according to their Marketing Authorization and Summary of Product Characteristics : Diuretics, beta-blockers, Angiotensin Converting Enzyme inhibitors, Angiotensin Receptor Blockers, Calcium Channel Blockers Throughout the study, choice of drugs in each therapeutic class is left on the investigator's initiative. All drugs of these classes may be used , no specific drug is tested in this study.
usual strategyOther
The implementation of antihypertensive therapy the current recommendations to reach the blood pressure target in usual care. Throughout the study, choice of drugs in each therapeutic class is left on the investigator's initiative. Combinations of different pharmacological classes can be tested in order to find the most effective and best tolerated combinations.
| Study group | Role | What they receive |
|---|---|---|
| blood pressure lowering algorithm | Experimental | enhanced strategy aiming to reduce systolic blood pressure to <135 mmHg Receives: Other: blood pressure lowering algorithm |
| usual strategy | Active comparator | usual strategy based on the usual care of routine care Receives: Other: usual strategy |
What is being measured
The primary outcome is the main question the study is designed to answer.
The main criterion is based on the quantitative assessment of White Matter Lesions (WML) volumes at the beginning and at the end of the study for each patient and each arm of the trial. The WML volume from the final MRI is compared to that of the initial
Measured: 36 months + 6 months max
Secondary outcomes (10)
Imaging criteria : changes in the number of large or confluent WML
Measured: 36 months+ 6 months max
Imaging criteria : changes in the volume of WML depending on their location (periventricular and deep white matter)
Measured: 36 months+ 6 months max
Imaging criteria : changes in the number of silent infarctus
Measured: 36 months+ 6 months max
Imaging criteria : changes in the number of microbleeds
Measured: 36 months+ 6 months max
Imaging criteria : evolution of brain volumes (gray matter, white matter, CSF, and regional volumes including hippocampus)
Measured: 36 months+ 6 months max
Clinical criteria: clinical criteria (changes in neuropsychological tests
Measured: 36 months
Clinical criteria: changes inwalking speed
Measured: 36 months
Clinical criteria: number of incident cases of dementia
Measured: 36 months
Number of incident cases of vascular events validated by an expert committee
Measured: 36 months
Clinical criteria: total mortality by cause
Measured: 36 months+ 6 months max
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2015 (estimated)
- Study startSep 2015
- Primary completion11 Sep 2028 (estimated)
- Study completion11 Sep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cerebrovascular DisordersStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 820 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Christophe TZOURIO, MD, PhD, Study director, Inserm U897 - Bordeaux UniversityOlivier HANON, MD, PhD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02472028
- Sponsor's protocol ID
- P100153
- Other IDs
- 2014 A00265-42
- Acronym
- LEOPOLD
- Status last verified
- Oct 2026
- First submitted
- 27 Apr 2015
- Last updated
- 29 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- LEukoaraiosis and blOod Pressure Reduction in OLD People
- ClinicalTrials.gov ID
- NCT02472028
- Acronym / sponsor ID
- LEOPOLD / P100153
- Conditions
- Cerebrovascular Disorders
- Keywords
- Cerebrovascular Disorders, Stroke, Antihypertensive Agents, Arterial Pressure, Memory Disorders
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 820 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Sep 2015 (actual)
- Primary completion
- 11 Sep 2028 (estimated)
- Study completion
- 11 Sep 2028 (estimated)
- First posted
- 15 Jun 2015 (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.
The purpose of the study is to test the hypothesis of slowing the progression of White Matter Lesions (WML) by lowering blood pressure (BP) in patients with cognitive complaints and a moderate to high grade of WML on brain MRI.
Detailed description
SCIENTIFIC BACKGROUND: White Matter Lesions (WML) are cerebrovascular abnormalities discovered on MRI that are associated with an increased risk of dementia. High blood pressure (BP) is a major risk factor for WML. WML are therefore key lesions in the causal chain linking vascular factors and dementia, particularly Alzheimer's disease.
However, it has not been shown that lowering BP could limit the progression of the WML in people with cognitive impairment.
OBJECTIVES: To test the hypothesis of slowing progression of WML by lowering BP in patients with memory complaints with a moderate to high grade of WML on brain MRI.
STUDY DESIGN: PROBE (Prospective randomized open blinded end-point) trial. Blind reading of both MRI for every patient in each group. After stratified randomization on age, sex and center, patients will be assigned to two strategies:
- Reinforced Group (RG): enhanced strategy aiming at a systolic BP <135 mmHg;
- Usual Group (UG): usual strategy based on the usual routine care.
SAMPLE SIZE: patients will be enrolled (410 in each arm) in 12 Memory Resources and Research Center (CMRR) with access to 1.5 T or more MRI.
CONDUCT OF THE STUDY:
Duration of the inclusion period: 96 months and 2 weeks. Patient participation duration: 36 months + 6 months max Total study duration: 11 years. Clinical and para-clinical evaluation: MRI as part of research at the beginning of the study and before the end of the study at 36 months + 6 months max (primary endpoint); Clinical evaluation of neuropsychological tests at the beginning of the study and yearly ; walking speed measurement single leg stance balance test ; repeated BP measurements; monitoring of neurological signs and symptoms; blood test at the beginning of the study (electrolytes, lipid profiles, fasting blood glucose, if not existing); MRI if not existing for validation of the inclusion criterion and performed in the ordinary course.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| blood pressure lowering algorithm | Experimental | Other: blood pressure lowering algorithmenhanced strategy aiming to reduce systolic blood pressure to <135 mmHg |
| usual strategy | Active comparator | Other: usual strategyusual strategy based on the usual care of routine care |
Who may qualify
- Ages
- 60 to 88 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 60 to 88 years old patients;
- Patient with cognitive complaint with MMSE ≥ 20performed within 6 months prior to enrollment (with or without dementia)
- Patient with a socio-educational level ≥ 3
- Presence of hyperintensities of moderate to high grade on the last MRI or old scan (grades C and D on the modified Scheltens scale, grades 2/3 Fazekas).
- Hypertension defined by a Systolic Blood Pressure (SBP) and / or a Diastolic Blood Pressure (DBP) ≥ 140/90 mmHg, treated or not
Key exclusion criteria (10 listed)
- Presence of severe orthostatic hypotension defined as a decrease of 30 mmHg in SBP standing within 3 minutes
- Contraindication to MRI (presence of ferromagnetic foreign body (especially some intracranial clips, some heart valves, intraocular foreign bodies, metal prosthesis), subject carrying pacemaker, claustrophobic participants)
- Severe diseases associated with a life expectancy of less than 3 months;
- Major physical impairments that can interfere with the feasibility of the tests (sight, hearing ...)
- Presence of another dementia different than Alzheimer's disease vascular dementia or mixed dementia,
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 |
|---|---|---|
| blood pressure lowering algorithmAlso: enhanced strategyThe treatments used in the "enhanced strategy" arm are those proposed by national (HAS2013, SFHTA2013) and international (ESH 2013) recommendations, according to their Marketing Authorization and Summary of Product Characteristics : Diuretics, beta-blockers, Angiotensin Converting Enzyme inhibitors, Angiotensin Receptor Blockers, Calcium Channel Blockers Throughout the study, choice of drugs in each therapeutic class is left on the investigator's initiative. All drugs of these classes may be used , no specific drug is tested in this study. | Other | blood pressure lowering algorithm |
| usual strategyThe implementation of antihypertensive therapy the current recommendations to reach the blood pressure target in usual care. Throughout the study, choice of drugs in each therapeutic class is left on the investigator's initiative. Combinations of different pharmacological classes can be tested in order to find the most effective and best tolerated combinations. | Other | usual strategy |
Primary outcome
The main criterion is based on the quantitative assessment of White Matter Lesions (WML) volumes at the beginning and at the end of the study for each patient and each arm of the trial. The WML volume from the final MRI is compared to that of the initial
Time frame: 36 months + 6 months max
10 secondary outcomes
Imaging criteria : changes in the number of large or confluent WML
Time frame: 36 months+ 6 months max
Imaging criteria : changes in the volume of WML depending on their location (periventricular and deep white matter)
Time frame: 36 months+ 6 months max
Imaging criteria : changes in the number of silent infarctus
Time frame: 36 months+ 6 months max
Imaging criteria : changes in the number of microbleeds
Time frame: 36 months+ 6 months max
Imaging criteria : evolution of brain volumes (gray matter, white matter, CSF, and regional volumes including hippocampus)
Time frame: 36 months+ 6 months max
Clinical criteria: clinical criteria (changes in neuropsychological tests
Time frame: 36 months
Clinical criteria: changes inwalking speed
Time frame: 36 months
Clinical criteria: number of incident cases of dementia
Time frame: 36 months
Number of incident cases of vascular events validated by an expert committee
Time frame: 36 months
Clinical criteria: total mortality by cause
Time frame: 36 months+ 6 months max
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Oct 2026.
Related trials for Cerebrovascular Disorders
Not yet recruiting
Temporal Interference Stimulation for Upper-Limb Motor Recovery in Early Subacute Stroke
Acute Ischemic Stroke
Not yet recruitingPhase 3
TicAgreLor Versus Placebo to Prevent Cerebral ISCHemia in anEuRysmal Low Grade SAH A Double Blinded Randomised Controlled Study
Subarachnoid Hemorrhage, Aneurysmal, Brain Ischemia
Active, not recruitingPhase 4
Effects of Sequential Therapy With Mexidol® (Intravenous) and Mexidol® FORTE 250 (Oral) on Functional Brain Activity Assessed by Functional Magnetic Resonance Imaging and Biochemical Parameters in Patients With Chronic Cerebral Ischemia: A Comparison of Patients With and Without Metabolic Disorders
Metabolic Abnormalities, Obesity & Overweight
Recruiting
Web-Based Tele-Rehabilitation Using Action Observation and Mirror Therapy for Subacute Stroke: A Randomized Controlled Trial
Stroke, Upper Extremity Paresis
Recruiting
Early Motor-Cognitive Integrative Training on Cognitive and Motor Performance in Patients With Aneurysmal Subarachnoid Hemorrhage
Subarachnoid Aneurysm Hemorrhage
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.
Christophe TZOURIO, MD, PhD contact
Christophe TZOURIO, MD, PhD study director
Inserm U897 - Bordeaux University
Olivier HANON, MD, PhD principal investigator
Assistance Publique - Hôpitaux de Paris
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing blood pressure lowering algorithm and usual strategy in people with Cerebrovascular Disorders, run by Assistance Publique - Hôpitaux de Paris at 2 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 7 inclusion and 10 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: looking for participants now, as of the sponsor's last update on 29 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Olivier HANON, MD, PhD (33 1 44 08 35 02, olivier.hanon@brc.aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The main criterion is based on the quantitative assessment of White Matter Lesions (WML) volumes at the beginning and at the end of the study for each patient and each arm of the trial. The WML volume from the final MRI is compared to that of the initial (time frame: 36 months + 6 months max). 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 29 Oct 2026.