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

February 15, 2021 updated by: Asmaa Nady Hussein, Assiut University

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

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 .

Study Overview

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 Type

Observational

Enrollment (Actual)

85

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Assiut, Egypt, Assiut university 71515
        • Assiut UNIVERSITY HOSPITAL

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

All B thalassemia parients who admitted to Clinical Hematology Unit - Internal Medicine Department at Assiut University Gospital

Description

Inclusion Criteria:

  • B thalassemia patients

Exclusion Criteria:

  • Diabetes mellitus
  • Hypertension
  • Obesity

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
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
serum samples used for doing the test by ELISA
serum samples used for doing the test by ELISA
serum samples used for doing the test by ELISA
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
serum samples used for doing the test by ELISA
serum samples used for doing the test by ELISA
serum samples used for doing the test by ELISA
Done by carotid doppler

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adiponectin
Time Frame: once (1 day)
Estimated by ElISA
once (1 day)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
HsC-reactive protein
Time Frame: once (1 day)
By ELISA
once (1 day)
Interleukin-6
Time Frame: once (1 day)
By ELISA
once (1 day)
carotid intima media thickness
Time Frame: once (1 day)
By carotid doppler
once (1 day)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 1, 2018

Primary Completion (Actual)

January 30, 2021

Study Completion (Actual)

February 15, 2021

Study Registration Dates

First Submitted

May 26, 2017

First Submitted That Met QC Criteria

May 30, 2017

First Posted (Actual)

May 31, 2017

Study Record Updates

Last Update Posted (Actual)

February 16, 2021

Last Update Submitted That Met QC Criteria

February 15, 2021

Last Verified

February 1, 2021

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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