Clinical trial NCT02472028: Blood Pressure Reduction to Limit the Evolution of Vascular Brain Lesions in Elderly Individuals
Official title: LEukoaraiosis and blOod Pressure Reduction in OLD People
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Cerebrovascular Disorders
Keywords: Cerebrovascular Disorders
Stroke
Antihypertensive Agents
Arterial Pressure
Memory Disorders
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2015-06-15
Enrollment: 820
Sex: ALL
Minimum age (years): 60
Maximum age (years): 88
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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;
* 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

Primary outcomes:
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
timeFrame: 36 months + 6 months max
Secondary outcomes:
measure: Imaging criteria : changes in the number of large or confluent WML
timeFrame: 36 months+ 6 months max
measure: Imaging criteria : changes in the volume of WML depending on their location (periventricular and deep white matter)
timeFrame: 36 months+ 6 months max
measure: Imaging criteria : changes in the number of silent infarctus
timeFrame: 36 months+ 6 months max
measure: Imaging criteria : changes in the number of microbleeds
timeFrame: 36 months+ 6 months max
measure: Imaging criteria : evolution of brain volumes (gray matter, white matter, CSF, and regional volumes including hippocampus)
timeFrame: 36 months+ 6 months max
measure: Clinical criteria: clinical criteria (changes in neuropsychological tests
timeFrame: 36 months
measure: Clinical criteria: changes inwalking speed
timeFrame: 36 months
measure: Clinical criteria: number of incident cases of dementia
timeFrame: 36 months
measure: Number of incident cases of vascular events validated by an expert committee
timeFrame: 36 months
measure: Clinical criteria: total mortality by cause
timeFrame: 36 months+ 6 months max
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Memory for Research and Resources Center / Neuroscience pole
state: Pellegrin Hospital Group
city: Paris
country: France
facility: Memory Resources Centre and South of Ile de France Search - Broca Hospital
Study officials:
affiliation: Inserm U897 - Bordeaux University
name: Christophe TZOURIO, MD, PhD
role: STUDY_DIRECTOR
affiliation: Assistance Publique - Hôpitaux de Paris
name: Olivier HANON, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: