Plain English Summary
Background and study aims
High blood pressure (hypertension) is a risk factor for mild deterioration in mental abilities and brain damage. The state of the brain structure can be assessed using a special form of MRI known as diffusion tensor imaging and blood flow in the brain can be assessed using functional MRI.
This study aims to identify the effect on brain structure and bloodflow of anti-hypertensive medication in hypertensive patients and healthy volunteers.
Who can participate?
Patients aged 40 - 59 years with hypertension-mediated organ damage can participate in the hypertension group. People aged 40 - 59 years who do not have hypertension will be included in the control group.
What does the study involve?
Participants will visit the test centre for MRI scanning and then be asked to wear a blood pressure monitor at home for 24 hours. Hypertensive patients will then be provided with blood pressure lowering medication to take once daily. Patients will have their blood pressure checked after two and four weeks to see if the medication is having any effect. After 12 weeks the assessments will be repeated.
What are the possible benefits and risks of participating?
Possible benifits of participating: additional diagnostic methods used in the present study can help your physician to improve and personalise your treatment strategy.
Possible risks of participating: all procedures are non-invasive, but require additional time. Patients recieving antihypertensive medications may expirience side-effects of the drug.
Where is the study run from?
A.Y. Kozhevnikov Clinic of Nervous Diseases (Russia)
When is the study starting and how long is it expected to run for?
December 2016 to December 2018
Who is funding the study?
Investigator initiated and funded
Who is the main contact?
Tatiana Ostroumova
t.ostroumova3@gmail.com
Trial website
Contact information
Type
Scientific
Primary contact
Ms Tatiana Ostroumova
ORCID ID
https://orcid.org/0000-0003-1499-247X
Contact details
I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation
8-2 Trubetskaya st.
Moscow
123007
Russian Federation
+7 9661210566
t.ostroumova3@gmail.com
Additional identifiers
EudraCT number
Nil known
ClinicalTrials.gov number
Nil known
Protocol/serial number
protocol №11-16
Study information
Scientific title
Observational study to assess cognitive functions, white matter hyperintensities, cerebral blood flow and fractional anisotropy in treatment-naive middle-aged hypertensive patients compared to normotensive controls and to assess the impact of 12-weeks single pill Perindopril/Indapamide treatment on those domains to improve personalized antihypertensive therapy
Acronym
Study hypothesis
1. Treatment-naive middle-aged hypertensive patients have worse executive functions, more white matter hyperintensities, lower cerebral blood flow and fractional anisotropy compared to normotensive controls
2. 12-weeks single pill Perindopril/Indapamide treatment improves blood pressure level, cognitive status and potentially has an impact on cerebral blood flow and fractional anisotropy
Ethics approval
Approved 14/12/2016, Ethics committee of I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (8-2 Trubetskaya st., Moscow, 119991, Russia; +7 495 609-14-00; iec@sechenov.ru), ref: 11-16
Study design
Single-centre observational study
Primary study design
Observational
Secondary study design
In parallel groups
Trial setting
Hospitals
Trial type
Prevention
Patient information sheet
Not available in web format, please use contact details to request a participant information sheet
Condition
Arterial hypertension
Intervention
All participants undergo a baseline assessment as follows:
1. Neuropsychological assessment (MoCA, verbal fluency test, TMT (parts A and B), 10-words list learning task, Stroop Color and Word Test)
2. 24-hour ambulatory blood pressure monitoring (BPLab monitoring system BP2005-01.04.00.2540, “Petr Telegin”, Russia): following SBP, DBP and pulse pressure (PP) data were provided: 24-h mean values and variability, daytime (07:00–23:00) mean values and variability, night time (23:00–07:00) mean values and variability
3. Brain magnetic resonance imaging (MAGNETOM Skyra 3.0 T, Siemens AG, Germany): T1, MPRAGE, T2 FLAIR, PASL, TOF 2D, DTI to evaluate white matter hyperintensities (Fazekas scale), cerebral blood flow in the cortical plates of frontal lobes and fractional anisotropy in 28 regions of interest
Non-hypertensive patients end participation at this point.
Hypertensive patients are prescribed with perindopril (5 mg) / indapamide (1.25 mg) single-pill combination, given once daily in the morning. If after 2 weeks of treatment office BP level is >140/90 mm Hg, Perindopril/Indapamide will be up-titrated to Perindopril (10 mg) / Indapamide (2.5 mg). If after 2 weeks of treatment the patient’s office BP level is still >140/90 mm Hg, the patient is excluded from the study. The follow-up period after reaching the target BP level was 12 weeks.
At follow-up the assessments are repeated.
Intervention type
Mixed
Phase
Drug names
Primary outcome measure
At baseline and follow-up
1. Blood pressure measured using sphygmomanometer
2. Cognitive function measured using MoCA, verbal fluency test, TMT (parts A and B), 10-words list learning task, Stroop Color and Word Test
3. Cerebral blood flow measured using fMRI
Secondary outcome measures
Fractional anisotropy measured using fMRI at baseline and follow-up
Overall trial start date
01/09/2016
Overall trial end date
15/12/2018
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
Hypertension group:
1. Age 40-59 years
2. Office SBP – 140–179 mmHg and/or DBP – 90–109 mmHg
3. Presence of at least one hypertension-mediated organ damage (heart – left ventricular hypertrophy assessed by echocardiogram, blood vessels – atherosclerotic plaques assessed by triplex scanning of the brachiocephalic arteries, kidneys – microalbuminuria and/or glomerular filtration rate according to CKD-EPI between 30-60 ml/min/1.73 m²)
4. Lack of antihypertensive treatment
Control group
1. Healthy men and women
2. Age 40-59 years
3. Absence of hypertension
Participant type
Mixed
Age group
Adult
Gender
Both
Target number of participants
140
Participant exclusion criteria
1. Body mass index ≥ 40 kg/m²
2. Pregnancy, lactation
3. Clinically significant heart disease (myocardial infarction, 2nd and 3rd degree atrio-ventricular block without artificial pacemaker, sinoatrial block, sick sinus syndrome, hypertrophic cardiomyopathy, aortic and mitral stenosis, chronic heart failure, angina pectoris)
4. Clinically significant liver disease
5. Clinically significant kidney disease (GFR according to CKD-EPI <30 ml/min / 1.73 m², hemodialysis, anuria)
6. Clinically significant respiratory organ disease (including bronchial asthma and chronic obstructive pulmonary disease)
7. Clinically significant immunological disease
8. Clinically significant endocrine disease (including diabetes mellitus)
9. Secondary hypertension
10. Gout
11. Mental illness and disorders, dementia, drug and alcohol abuse
12. Severe peripheral vascular diseases (including Raynaud's syndrome)
13. Metabolic acidosis
14. Refractory hypokalemia
15. Clinically significant neurological diseases (including stroke and transient ischemic attack)
16. Surgical operation in the previous 3 months (excluding dental or plastic surgery)
17. Use of any medication (including regular intake of antihypertensive treatment) that could have affected the results of the study for 12 weeks before enrollment, at the time of enrollment and until the end of the study
Recruitment start date
15/12/2016
Recruitment end date
30/11/2017
Locations
Countries of recruitment
Russian Federation
Trial participating centre
A.Y. Kozhevnikov Clinic of Nervous Diseases
11-1, Rossolimo St.
Moscow
119021
Russian Federation
Sponsor information
Organisation
Sechenov University
Sponsor details
I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation
8-2 Trubetskaya st.
Moscow
119991
Russian Federation
+7 (495) 609-14-00
expedition@mma.ru
Sponsor type
University/education
Website
Funders
Funder type
Other
Funder name
Investigator initiated and funded
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Planned publication in a high-impact peer-reviewed journal.
IPD sharing statement:
All data generated or analysed during this study will be included in the subsequent results publication.
Intention to publish date
15/12/2020
Participant level data
Other
Basic results (scientific)
Publication list