Human IgGs and Endothelial Function in Vivo in Humans

Common Variable Immunodeficiency Clinical Trial

— HIGH  

Official title:

Effects of Intravenous Human Polyclonal Immunoglobulins G Infusion on Endothelial Function and Insulin Sensitivity in Humans

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03534479
• Other study ID #: HypoIgG1
• Status: Completed
• Phase: N/A
• Start date: April 2010
• Est. completion date: April 2013

Study information

• Verified date: May 2018
• Source: Federico II University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: April 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Common Variable Immunodeficiency

Exclusion Criteria:

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

Related Conditions & MeSH terms

• Common Variable Immunodeficiency
• Immunologic Deficiency Syndromes

Intervention

Drug:
• Polyclonal IgG
Measurement of vascular reactivity before and after Infusion of plyclonal Immunoglobulins G in patients with Common variable immunodeficiency

Locations

Country	Name	City	State
Italy	Federico II University Hospital	Napoli

Sponsors (1)

Lead Sponsor	Collaborator
Federico II University

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Endothelial Mediated Vascular Reactivity	Change in vascular reactivity measured by Flow Mediated Dilation of the brachial artery	1 day, 1 week, 2 weeks or three weeks after polyclonal IgG infusion
Secondary	Change in insulin sensitivity	Change in insulin sensitivity measured as change in the Homeostasis model assessment (HOMA-IR) index	1 day, 1 week, 2 weeks or three weeks after polyclonal IgG infusion