Condition category
Circulatory System
Date applied
09/11/2016
Date assigned
12/12/2016
Last edited
07/12/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Arterial hypertension (HTA) is high blood pressure in the vessels that carry blood from the heart to the body's tissues. It is a serious public health problem and is a major risk factor for cardiovascular (heart) disease, cerebrovascular disease (e.g., stroke) and kidney failure, which are major causes of death. Studies have found that there is a relationship between high blood pressure and atherosclerosis (the build-up of fatty material inside the arteries). This situation highlights the need to develop useful and easily accessible diagnostic tools for clinical practice. The intima/media thickness (IMT) is a measurement of the innermost two layers of carotid artery wall. It is an excellent marker for atherosclerosis and cardiovascular disease. The aims of this study are to compare the levels of LRP1 protein in circulating monocytes (white blood cells) from patients with high or normal blood pressure, to determine the relationship between LRP1 levels and IMT, and to find out whether LRP1 levels can be used as a marker for atherosclerosis.

Who can participate?
Mexicans age 40-70 with high or normal blood pressure

What does the study involve?
Participants’ body measurements are taken, including their height and weight, and their blood pressure is measured. Their IMT is measured with an ultrasound device. Blood samples are collected after fasting for 12 hours to measure LRP1 levels.

What are the possible benefits and risks of participating?
If a participant is found to have hypertension, increased IMT, high blood cholesterol and high LRP1 levels, they may have atherosclerosis. Knowing these results the doctor can give a preventive treatment to avoid cardiovascular and cerebrovascular disease. IMT is assessed with ultrasound, which does not expose the patient to any risk.

Where is the study run from?
National Institute of Cardiology "Ignacio Chavez" (Mexico)

When is the study starting and how long is it expected to run for?
October 2011 to July 2014

Who is funding the study?
National Council of Science and Technology (Mexico)

Who is the main contact?
Dr Claudia Huesca-Gomez
c_huesca@yahoo.com

Trial website

Contact information

Type

Scientific

Primary contact

Dr Claudia Huesca-Gomez

ORCID ID

http://orcid.org/0000-0002-6806-3484

Contact details

Juan Badiano No 1
Col. Sección XVI
C.P.14080
México City
14080
Mexico
(52-55) 55 73 29 11 Ext.1278
c_huesca@yahoo.com

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

JTRM-D-16-00728

Study information

Scientific title

Monocyte low-density lipoprotein receptor-related protein 1 (LRP1) expression correlates with intima-media thickening in Mexican hypertensive patients

Acronym

LRP1 hypertensive

Study hypothesis

Arterial hypertension, one of major risk factors for atherosclerosis, contributes to foam cell formation in the vasculature though low-density lipoprotein receptor-related protein 1 (LRP1) upregulation. The purpose of this work was to study the association between monocyte LRP1 mRNA expression and LRP1 protein levels and intima/media thickness in the carotid artery (IMT) of patients with essential hypertension

If the LRP1 receptor modulates the uptake of c-LDL associated with hypertension, an increased IMT is expected to be found in hypertensive patients along with an overexpression of LRP1 in peripheral blood monocytes

The aims of this study were:
1. To compare LRP1 expression levels in circulating monocytes from patients with essential hypertension against normotensive patients
2. To determine the relationship between LRP1 overexpression and arterial intima/media thickening to assess if monocyte LRP1 expression is a potential biomarker for atherosclerosis

Ethics approval

Commission of bioethics of the INC Ignacio Chavez, 16/03/2010, ref: 10-665

Study design

Single-center observational case-control study

Primary study design

Observational

Secondary study design

Case-control study

Trial setting

Hospitals

Trial type

Screening

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet

Condition

Arterial hypertension

Intervention

The population is recruited from the outpatient Service of the National Institute of Cardiology "Ignacio Chavez", where the hypertension diagnosis was made by a medical specialist. The subjects underwent anthropometric measurements determining their height in meters (m) weight in kilograms (kg). Blood pressure is measured using a mercury sphygmomanometer following the recommendations of the VII Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC VII). Systolic and diastolic blood pressures are measured after rest for at least 10 min, and the average of the second and third measurements is recorded for analysis. Hypertension is defined as systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg or a previous clinical diagnosis of essential hypertension.

A specialist in sonography resolution assesses the intima/media thickness in the carotid artery, all measurements are performed with a Sonosite Micromax ultrasound device coupled to a 13 MHz multifrequency high-resolution linear transducer.

Blood samples were collected after a fasting period of 12 hours. Commercial enzymatic methods were used to determine circulating TC and TG, HDL-C, LDL-C. Angiotensin II was determined by capillary electrophoresis and C-reactive protein was determined by nephelometry. Peripheral blood mononuclear cell (PBMCs) are isolated from blood collected in EDTA using the Ficoll separation method.

Total RNA was extracted using monocyte TripureTM isolation reagent (Roche Molecular Biochemicals) followed by a reverse transcription reaction.

LRP1 gene expression and HPRT (endogenous gene) were quantified using a commercial kits "TaqMan Gene Expression" employing 7300 Real Time PCR System (Applied Biosystems) equipment. Total protein was extracted from monocytes using TriPureTM reagent (Roche Molecular Biochemicals). Membranes were incubated with monoclonal antibody against human LRP1 (85kDa β-chain). The QuantityOne program was used to quantify the bands present in the membranes.

Intervention type

Other

Phase

Drug names

Primary outcome measures

1. Blood pressure (normotensive or hypertensive), measured using a mercury sphygmomanometer at 10 months
2. LRP1 gene expression, quantified using a "TaqMan Gene Expression" commercial kit and 7300 Real Time PCR System at 3 months
3. LRP1 protein, analyzed by western blot at 6 months
4. The intima/media thickness in the carotid artery, assessed with a Sonosite Micromax ultrasound device coupled to a 13 MHz multifrequency high-resolution linear transducer at 10 months

Secondary outcome measures

N/A

Overall trial start date

01/10/2011

Overall trial end date

25/07/2014

Reason abandoned

Eligibility

Participant inclusion criteria

Control group:
1. Normal pressure up to 120/80 mmHg
2. Mexican by birth, with at least two previous generations of Mexican origin
3. Agree to participate in the research protocol
4. Age 40-70 years

Hypertensive group:
1. Blood pressure > 140/90mmHg
2. Mexican by birth, with at least two previous generations of Mexican origin
3. Agree to participate in the research protocol

Participant type

Mixed

Age group

Adult

Gender

Both

Target number of participants

200 Mexican subjects (91 were normotensive and 109 were hypertensive)

Participant exclusion criteria

Control group:
1. Have a history of cardiovascular disease
2. Have type 1 or 2 diabetes.
3. Have a chronic degenerative disease
4. Treatment with lipid-lowering medications

Hypertensive group:
1. Treatment with lipid-lowering medications
2. Have type 1 or 2 diabetes
3. Have a chronic degenerative disease

Recruitment start date

24/07/2013

Recruitment end date

27/02/2014

Locations

Countries of recruitment

Mexico

Trial participating centre

National Institute of Cardiology "Ignacio Chavez"
Juan Badiano No 1 Col. Sección XVI, C.P.
México City
14080
Mexico

Sponsor information

Organisation

National Institute of Cardiology "Ignacio Chavez"

Sponsor details

Juan Badiano No 1
Col. Sección XVI
C.P.14080
México City
14080
Mexico
(52-55) 55 73 29 11 Ext.1278
c_huesca@yahoo.com

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Government

Funder name

Consejo Nacional de Ciencia y Tecnología

Alternative name(s)

National Council of Science and Technology, Mexico, CONACYT

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

Mexico

Results and Publications

Publication and dissemination plan

The results will be published in the first quarter of 2017.

IPD sharing plan
The datasets generated during and/or analysed during the current study will be available upon request from Dr Claudia Huesca-Gomez (c_huesca@yahoo.com).

Intention to publish date

21/01/2017

Participant level data

Available on request

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes