Human IgGs and Endothelial Function in Vivo in Humans

NCT ID: NCT03534479

Last Updated: 2018-05-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-04-30
• Study Completion Date: 2013-04-30

Brief Summary

Endothelial dysfunction and insulin resistance play a key role in the onset and development of atherosclerosis, cardiovascular diseases, and diabetes. Data in mice models have recently demonstrated that circulating immunoglobulins G (IgG) could be involved in the process. Patients with common variable immunodeficiency (CVID), who are characterized by low circulating levels of IgG, might represent an ideal model to clarify the role played in vivo in humans by circulating IgG. Polyclonal IgG, obtained from multiple donors, given intravenously (IVIgG), are used to treat various immunodeficiencies and autoimmune diseases, including CVID. By using this disease and its treatment by IVIgG as a model, aim of the current study is to clarify whether IgG affect endothelial function and insulin sensitivity in humans in vivo and whether the action of IgG on the endothelium involves a direct interaction with the endothelial cells.

Detailed Description

For this purposes, 24 patients with CVID, receiving the last therapeutic dose of IVIgG infusion 5-weeks before the baseline measurements (CVID-IVIgG group), are studied. In all subjects, endothelial function is evaluated as flow mediated dilation (FMD) of the brachial artery, measured by ultrasonographic technique at baseline and 1, 7, 14, and 21 days after IVIgG infusion. FMD is also measured in a group of IVIgG naive CVID patients (number of patients recruited depending on availability) and a group of control healthy subjects. The latter FMD measurements serve only as a mere reference of pathological or normal values in condition of deficiency or normal levels of circulating IgG and are not used for primary outcome evaluation. To dissect further the mechanisms of improved endothelial function after IVIgG infusion, we investigate the role of human IgG on the production of Nitric Oxide (NO) in vitro on Human Coronary Artery Endothelial Cells (HCAEC) isolated from normal human coronary arteries.

Conditions

Common Variable Immunodeficiency

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

CVID-IVIgG, polyclonal IgG i.v. infusion

The patients of the CVID-IVIgG, polyclonal IgG infusion, group are studied five weeks from their last therapeutic polyclonal IgG i.v. infusion (IVIgG). On the mornings of day 0, vascular reactivity of the brachial artery, assessed as Flow mediated dilation (FMD), is measured and blood collected for biochemistry (baseline). Immediately after the FMD measurements and the blood collection, the 24 patients receive half dose of IVIgG necessary to treat their disease (400 mg/kg body weight in 10% solution). Twenty-four hours later, before infusing the second half of the dose of the IVIgG, vascular reactivity is again measured and blood collected. Vascular reactivity is again measured 1, 2, and 3 weeks after the first IVIgG infusion.

Group Type: EXPERIMENTAL

Polyclonal IgG

Intervention Type: DRUG

Measurement of vascular reactivity before and after Infusion of plyclonal Immunoglobulins G in patients with Common variable immunodeficiency

Interventions

Polyclonal IgG

Measurement of vascular reactivity before and after Infusion of plyclonal Immunoglobulins G in patients with Common variable immunodeficiency

Intervention Type: DRUG

Other Intervention Names

Immunoglobulins

Eligibility Criteria

Inclusion Criteria

• Common Variable Immunodeficiency

Exclusion Criteria

• Cancer, liver Cirrhosis, recent acute myocardial infarction, treatment with nitroderivates, Reynaud syndrome, heart failure

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Federico II University

OTHER

Sponsor Role: lead

Responsible Party

RAFFAELE NAPOLI

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

RAFFAELE NAPOLI, MD

Role: PRINCIPAL_INVESTIGATOR

1990

Locations

Federico II University Hospital

Napoli, , Italy

Countries

Italy

Other Identifiers

HypoIgG1

Identifier Type: -

Identifier Source: org_study_id