Adiponectin, IL-6 and hsC-RP in Relation to Carotid Intima-media Thickness in B-thalassemia Patients

Sponsor

Assiut University (Other)

Overall Status

Completed

CT.gov ID

NCT03170245

Collaborator

(none)

Enrollment

Location

30.5

Actual Duration (Months)

2.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Every year, 100,000 neonates are born with hemoglobinopathies around the world. Thalassemia is the most common heterogeneous disease of the human being . It is a disease of high prevalence in Mediterranean, Indian, North Chinese, and Pacific populations. Recently, the quantity and quality of the life of these patients have been significantly improved by regular transfusion and iron chelating therapy .

Condition or Disease	Intervention/Treatment	Phase
Thalassemia	Diagnostic Test: Interleukin-6 Diagnostic Test: HsC-RP Diagnostic Test: Adiponectin level Diagnostic Test: Carotid intima media thickness

Detailed Description

β-thalassemia result from a decrease in β- globin chains which result in a relative excess of α-globin chains . Approximately 1.5% of the population is estimated to be carriers for β-thalassemia . Around 60,000 new births are recorded to be affected by β-thalassemia per year in the world . In Egypt, it was estimated that 1000/1.5 million live births per year suffer from thalassemia; β -thalassemia is the most common type, with a carrier rate starting from 5.3%-9% . Depending on severity of hematological and clinical conditions, β-thalassemia is classified into three types, namely, β-thalassemia minor (β-TMI) (also called as carrier), β-thalassemia intermedia (β-TI) and β-thalassemia major (β-TM). The clinical severity of β-thalassemia intermedia has ranged from asymptomatic carrier state to severe transfusion-dependent type. β-Thalassemia minor is clinically asymptomatic but can be characterized by specific hematological features .

A high incidence of thromboembolic event has been observed in patients with β -thalassemia. Endothelial dysfunction occurred in those patients was attributed to peroxidative tissue injury because of continuous blood transfusions . Carotid atherosclerosis was positively associated with serum ferritin independent of traditional cardiovascular risk factors and transfusion-related iron overload in β-thalassemia major (β-TM) has been associated with the onset of cardiovascular complications, including cardiac dysfunction and vascular anomalies. Increased iron overload has also been reported in patients with non-transfusion dependent thalassemia (NTDT) Direct iron-related injury is responsible for different kinds of cardiovascular abnormalities, including progressive worsening of diastolic and systolic ventricular function, increased arterial stiffness and pulmonary hypertension .

It has previously demonstrated that both patients with β-TM and β-TI exhibit a global impairment of arterial vasorelaxation and increased carotid intima-media thickness (cIMT) as compared with control healthy subjects , those findings strongly support the notion that the severe arterial dysfunction in thalassemia may indicate an additional clinical vulnerability for venous thromboembolism. Epidemiologically, vascular events appear at a relatively young age with a four times higher incidence in β-TI as compared with β-TM patients . Carotid intima-media thickness is related both with incident and prevalent cardiovascular disease and is accepted measure of subclinical atherosclerosis . It also increases the risk for future myocardial infarction (MI) .

Lipid abnormalities have been detected in different types of β -thalassemia, and also in various hematological disorders including sickle cell disease, glucose-6-phosphate dehydrogenase (G6PD) deficiency, spherocytosis, aplastic anemia and myelodysplastic syndrome . Patients with β - thalassemia are at risk of developing premature atherosclerosis because of those abnormalities .

Inflammatory biomarkers including C-reactive proteins and cytokines (IL-6) are found to be increased in various inflammatory conditions and have been used by a number of workers as biomarker of inflammation in thalassemia . The iron laden insult to the tissues in transfusion dependent thalassemic patients has been monitored using the high sensitive C-reactive proteins as biomarker of inflammation and vascular risk .

High Sensitive C-reactive protein(hsC-RP)is clinically proven as a method to predict vascular risk and to enhance event rates in clinical trials. As hsC-RP and IL-6 levels measured in apparently healthy populations also predict future vascular risk; hsC-RP and IL-6 levels have been shown to correlate with endothelial dysfunction, arterial stiffness, and extent of subclinical atherosclerosis . IL-6 signaling has also been linked to plaque initiation and destabilization , to microvascular flow dysfunction , and to adverse outcomes in the setting of acute ischemia .

Adiponectin, an adipose tissue secreted protein, has been well recognized to exhibit insulin-sensitizing, anti-inflammatory and anti-atherosclerotic properties . Its level is associated with atherosclerosis markers such as inflammation, oxidative stress, and endothelial dysfunction . Its anti-inflammatory action, resulting in decreased production and inhibition of tumor necrosis factor-α (TNF-α) action, decreased IL-6 production, and human studies previously reported an inverse association between adiponectin level and C-RP , TNF-α and IL-6 .

Adiponectin varies according to body mass index with lower levels in obese individuals , in type 2 diabetes mellitus (T2DM) and in hypertensive patients.

Circulating low adiponectin levels (hypoadiponectinemia) is considered an independent risk factor for endothelial dysfunction and modulating vessel wall health . It has been correlated with elevated risk factors of atherosclerotic cardiovascular disease and associated with hypertension, dyslipidemia, and inflammation in both the general population and in diabetic patients .

Study Design

Study Type:

Observational

Actual Enrollment :

85 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

Adiponectin, Interleukin-6 (IL-6) and High Sensitive C-reactive Protein (hsC-RP) in Relation to Carotid Intima-media Thickness in B-thalassemia Patients

Actual Study Start Date :

Aug 1, 2018

Actual Primary Completion Date :

Jan 30, 2021

Actual Study Completion Date :

Feb 15, 2021

Arms and Interventions

Arm	Intervention/Treatment
B thalassemia group Laboratory investigations : complete blood count renal and liver function tests serum ferritin lipid profile Interleukin -6 HsC-RP Adiponectin level Imaging : Abdominal ultrasound Echocardiography Carotid intima media thickness	Diagnostic Test: Interleukin-6 serum samples used for doing the test by ELISA Diagnostic Test: HsC-RP serum samples used for doing the test by ELISA Diagnostic Test: Adiponectin level serum samples used for doing the test by ELISA Diagnostic Test: Carotid intima media thickness Done by carotid doppler
Control group Laboratory investigations : complete blood count renal and liver function tests serum ferritin lipid profile Interleukin -6 HsC-RP Adiponectin level Imaging : Abdominal ultrasound Echocardiography Carotid intima media thickness	Diagnostic Test: Interleukin-6 serum samples used for doing the test by ELISA Diagnostic Test: HsC-RP serum samples used for doing the test by ELISA Diagnostic Test: Adiponectin level serum samples used for doing the test by ELISA Diagnostic Test: Carotid intima media thickness Done by carotid doppler

Arm

Intervention/Treatment

B thalassemia group

Laboratory investigations : complete blood count renal and liver function tests serum ferritin lipid profile Interleukin -6 HsC-RP Adiponectin level Imaging : Abdominal ultrasound Echocardiography Carotid intima media thickness

Diagnostic Test: Interleukin-6