Condition category
Circulatory System
Date applied
30/01/2020
Date assigned
06/02/2020
Last edited
06/02/2020
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting
Publication status
Results overdue

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

https://www.sechenov.ru/eng/

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

Publication citations

Additional files

Editorial Notes

06/02/2020: Trial’s existence confirmed by Ethics committee of I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation.