Human IgGs and Endothelial Function in Vivo in Humans (HIGH)

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

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.

Study Overview

• Status: Completed
• Conditions: Common Variable Immunodeficiency
• Intervention / Treatment: Drug: Polyclonal IgG

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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Napoli, Italy, 80131
    • Federico II University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Common Variable Immunodeficiency

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Federico II University
• Investigators: Principal Investigator: RAFFAELE NAPOLI, MD, 1990

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2010
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): April 1, 2013

Study Registration Dates

• First Submitted: May 10, 2018
• First Submitted That Met QC Criteria: May 22, 2018
• First Posted (Actual): May 23, 2018

Study Record Updates

• Last Update Posted (Actual): May 23, 2018
• Last Update Submitted That Met QC Criteria: May 22, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immunologic Deficiency Syndromes; Immune System Diseases; Common Variable Immunodeficiency; Physiological Effects of Drugs; Immunologic Factors; Immunoglobulins
• Other Study ID Numbers: HypoIgG1

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
• product manufactured in and exported from the U.S.: No