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

• ClinicalTrials.gov Identifier: NCT03534479
• Recruitment Status: Completed
• First Posted: May 23, 2018
• Last Update Posted: May 23, 2018
• Sponsor: Federico II University
• Information provided by (Responsible Party): RAFFAELE NAPOLI, Federico II University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Common Variable Immunodeficiency	Drug: Polyclonal IgG	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Effects of Intravenous Human Polyclonal Immunoglobulins G Infusion on Endothelial Function and Insulin Sensitivity in Humans
• Actual Study Start Date: April 2010
• Actual Primary Completion Date: April 2013
• Actual Study Completion Date: April 2013

Arms and Interventions

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 Name: Immunoglobulins

Outcome Measures

Primary Outcome Measures :

1. Change in Endothelial Mediated Vascular Reactivity [ Time Frame: 1 day, 1 week, 2 weeks or three weeks after polyclonal IgG infusion ]
   Change in vascular reactivity measured by Flow Mediated Dilation of the brachial artery

Secondary Outcome Measures :

1. Change in insulin sensitivity [ Time Frame: 1 day, 1 week, 2 weeks or three weeks after polyclonal IgG infusion ]
   Change in insulin sensitivity measured as change in the Homeostasis model assessment (HOMA-IR) index

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• Common Variable Immunodeficiency

Exclusion Criteria:

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

Contacts and Locations

Locations

Italy

Federico II University Hospital

Napoli, Italy, 80131

Sponsors and Collaborators

Federico II University

Investigators

• Principal Investigator: RAFFAELE NAPOLI, MD; 1990

More Information

• Responsible Party: RAFFAELE NAPOLI, Associate Professor, Federico II University
• ClinicalTrials.gov Identifier: NCT03534479
• Other Study ID Numbers: HypoIgG1
• First Posted: May 23, 2018
• Last Update Posted: May 23, 2018
• Last Verified: May 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Common Variable Immunodeficiency; Immunologic Deficiency Syndromes; Immune System Diseases; Immunoglobulins; Immunologic Factors; Physiological Effects of Drugs