Glycoxidation, Arterial Biomechanics, and Target Organ Damage

NCT06325800 | Recruiting

• 2 other identifiers: 2021401/2023007Grant
• Study Type: observational
• Target: 500
• Locations: 1 country
• Sites: 1

Brief Summary

Vascular target organ damage (TOD), defined as structural or functional deleterious changes in large and small arteries, is related to unfavorable arterial biomechanics, atherosclerosis and arteriosclerosis. Endothelial dysfunction due to unfavorable redox and glycation states on the bases of these phenomena. However, little is known about the role of glycoxidation on arterial biomechanics and TOD in apparently healthy individuals. The main hypothesis is that glycation and glycoxidation status are associated with arterial biomechanical abnormalities and TOD in patients with moderate to high cardiovascular risk. This is an observational, ambispective, and multicenter project that will include non-smoking patients over 18 years, without diabetes mellitus or established cardiovascular disease. Demographic, epidemiological, and clinical-anthropometric variables will be collected, including data from ambulatory blood pressure monitoring. The investigators will measure the serum percentage of glycated hemoglobin, glycated albumin, and fructosamine levels; along with quantification of skin advanced glycation and glycoxidation end productos (AGEs). Plasma concentration, activity, and structure of catalase, glutathione peroxidase, and superoxide dismutase in relation to the patient's glycation and glycoxidation status will be also evaluated. Concurrently, several biomechanical parameters will be assessed in the Common, Internal Carotid Artery, and distal limb arteries using ultrasound exploration. Incipient microvasculature damage will be also evaluated by retinal image. Patients will be followed up for the development of arterial biomechanical abnormalities and TOD, along with cardiovascular events.

Conditions

Oxidative Stress; Cardiovascular Risk; Target Organ Damage

Keywords

glycation; antioxidant; target organ damage; arterial biomechanic; carotid; glycoxidation

Outcome Measures

Primary Outcomes (10)

• Assessment of redox status (1)

  Evaluation of thiobarbituric acid reactive substances (TBARS) levels as a measure of lipid peroxidation

  Present, two, four years and final (5 years)

• Assessment of redox status (2)

  Evaluation of reduced thiol levels as a measure of protein oxidation

  Present, two, four years and final (5 years)

• Evaluation of glycation status (1)

  Measurement of serum fructosamine and glucose levels

  Present, two, four years and final (5 years)

• Evaluation of glycation status (2)

  Measurement of the percentage of serum glycated hemoglobin

  Present, two, four years and final (5 years)

• Evaluation of glycation status (3)

  Estimation of the percentage of serum glycated albumin

  Present, two, four years and final (5 years)

• Evaluation of glycation status (4)

  Quantification of skin advanced glycation end products (AGEs)

  Present, two, four years and final (5 years)

• Assessment of Glycoxidation status (1)

  Levels of thiobarbituric acid reactive substances (TBARS) also as an estimation of dicarbonyl levels from glycoxidation

  Present, two, four years and final (5 years)

• Assessment of Glycoxidation status (2)

  Quantification of skin advanced glycation end products (AGEs) also as an estimation of the levels of some glycoxidation byproducts

  Present, two, four years and final (5 years)

• Quantification of arterial targen organ damage (TOD) during the follow-up (1)

  Number of patients and severity (Arterial TOD considered as carotid intima-media thickness \>0.9 mm, cholesterol plaque, carotid stenosis, carotid-femoral pulse wave velocity \>10 m/s, pulse pressure \>60 mmHg, ankle-Brachial Index \<0.9 or \>1.3 hypertensive retinopathy)

  Present, two, four years and final (5 years)

• Quantification of arterial targen organ damage (TOD) during the follow-up (2)

  Number needed to treat (NNT) of consultations and exploration time to detect abnormalities in arterial biomechanics and target organ damage (TOD)

  two, four years and final (5 years)

Secondary Outcomes (1)

• Evaluation of cardiovascular disease during the follow-up

  two, four years and final (5 years)

Study Arms (2)

Controls

Patients with Arterial biomechanics values lower than or equal to the 50th percentile of the distribution (measured as carotid stiffness by ultrasound elastography, distensibility and stress, flow velocity and vascular resistance), AND Absence of vascular target organ damage (considered as carotid intima-media thickness \>0.9 mm, cholesterol plaque, carotid stenosis, carotid-femoral pulse wave velocity \>10 m/s, pulse pressure \>60 mmHg, ankle-Brachial Index \<0.9 or \>1.3, hypertensive retinopathy) AND Absence of cardiovascular disease (cardiovascular events, cerebrovascular events, hospital admissions, consultations, death, disability)

Cases

Patients with Arterial biomechanics values higher than the 50th percentile of the distribution (measured as carotid stiffness by ultrasound elastography, distensibility and stress, flow velocity and vascular resistance), OR Presence of vascular target organ damage (considered as carotid intima-media thickness \>0.9 mm, cholesterol plaque, carotid stenosis, carotid-femoral pulse wave velocity \>10 m/s, pulse pressure \>60 mmHg, ankle-Brachial Index \<0.9 or \>1.3, hypertensive retinopathy) OR Presence of cardiovascular disease (cardiovascular events, cerebrovascular events, hospital admissions, consultations, death, disability)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients belonging to the health area of Santiago de Compostela and Barbanza (A Coruña, Spain), referred from primary care and hospital services to the Cardiovascular Risk and Hypertension Unit of the Internal Medicine Department at the reference hospital.

You may qualify if:

• Patients aged 18 years or older.
• Moderate to high Cardiovascular Risk estimated by SCORE2OP.
• Signed written consent for participation in the study.

You may not qualify if:

• Absence of current smoking habit and in the last 6 months.
• High-risk alcohol consumption (More than 10 and 20 g/day in women and men, respectively).
• Presence of Diabetes mellitus.
• Established cardiovascular disease, including heart failure, ischemic heart disease, valvular heart disease, atrial fibrillation, peripheral artery disease, and cerebrovascular disease.

Sponsors & Collaborators

• Complejo Hospitalario Universitario de Santiago: lead
• Instituto de Investigación Sanitaria de Santiago de Compostela: collaborator
• Instituto de Salud Carlos III: collaborator
• University of Santiago de Compostela: collaborator
• Hospital de Barbanza: collaborator

Study Sites (1)

Complejo Hospitalario Universitario de Santiago de Compostela

Santiago de Compostela, A Coruña, 15706, Spain

RECRUITING

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Biospecimen

Retention: SAMPLES WITHOUT DNA

blood (plasma, serum), urine, salive, skin (no invasive)

Central Study Contacts

Nestor Vazquez-Agra, PhD

CONTACT

0034981950000; nestor.vazquez.agra@sergas.es

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: OTHER
• Target Duration: 5 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 16, 2024
• First Posted: March 22, 2024
• Study Start: January 1, 2024
• Primary Completion: December 31, 2024
• Study Completion (Estimated): December 31, 2029
• Last Updated: April 9, 2024

Record last verified: 2024-04

Locations

ES (1)