Clinical trial NCT03534479: Human IgGs and Endothelial Function in Vivo in Humans
Official title: Effects of Intravenous Human Polyclonal Immunoglobulins G Infusion on Endothelial Function and Insulin Sensitivity in Humans
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Common Variable Immunodeficiency
Lead sponsor: Federico II University
Sponsor class: OTHER
First posted: 2018-05-23
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: Inclusion Criteria:

* Common Variable Immunodeficiency

Exclusion Criteria:

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

Primary outcomes:
measure: Change in Endothelial Mediated Vascular Reactivity
timeFrame: 1 day, 1 week, 2 weeks or three weeks after polyclonal IgG infusion
Secondary outcomes:
measure: Change in insulin sensitivity
timeFrame: 1 day, 1 week, 2 weeks or three weeks after polyclonal IgG infusion
Other outcomes:
Locations:
city: Napoli
country: Italy
facility: Federico II University Hospital
Study officials:
affiliation: 1990
name: RAFFAELE NAPOLI, MD
role: PRINCIPAL_INVESTIGATOR
References: