EFFECTS OF RIFAXIMIN, BY MODULATION OF THE GUT MICROBIOTA, ON MARKERS OF SYSTEMIC INFLAMMATION IN PATIENTS WITH COMMON VARIABLE IMMUNODEFICIENCY - AN EXPLORATORY OPEN-LABEL RANDOMIZED CONTROLLED TRIAL

INTERVENTION: Trade Name: Xifaxan Pharmaceutical Form: Coated tablet CONDITION: Adult patients with the diagnosis of Common variable deficiency and fulfill the inclusion and exclusion criteria, will be invited to participate in the study. Therapeutic area: Diseases [C] ‐ Immune System Diseases [C20] PRIMARY OUTCOME: Main Objective: To investigate if intervention with antibiotics (i.e. Rifaximin) modifies markers of systemic inflammation by alteration of the gut microbiota. Primary end point(s): Primary Endpoint ; The primary endpoint will be time‐dependent changes in inflammatory and anti‐inflammatory mediators in plasma, serum, PBMC and whole blood.; The three most important markers will be:; • Serum levels of soluble CD14 [sCD14] as marker of gut leakage/systemic endotoxin exposure.; • C‐reactive protein [CRP] as a reliable marker of up‐stream inflammation.; • Serum levels of tumor necrosis factor [TNF]a which are known to be elevated in CVID patients (Aukrust, Lien et al. 1996); In addition we will examine (i) markers of endothelial cell activation [e.g., pentraxin‐3, von willebrand factor], (ii) markers of macrophage activation [e.g., neopterin, sCD163] (iii) inflammatory cytokines [e.g., interleukin (IL)‐1ß, IL‐6, IL‐8 and IL‐8], (iv) anti‐inflammatory cytokines [e.g. IL‐10, transforming growth factor ß], (v) chemokines [e.g., CCL5, CCL19, CCL21, CXCL8, CXCL16], (vi) additional markers of gut leakage[sTLR2, high‐mobility group box 1 protein, endotoxins] and (vii) T cell subpopulations [e.g., Tregs, naïve T cells, memory T cells], ; Secondary Objective: Not Applicable Timepoint(s) of evaluation of this end point: After Treatment: day 14 and 6 weeks after ended treatment. SECONDARY OUTCOME: Secondary end point(s): Secondary Endpoints ; • Compositional and time‐dependent changes of the gut microflora, FA composition and bacterial metabolites. ; • Serum SCFA and overall FA composition ; Timepoint(s) of evaluation of this end point: After Treatment day 14 and 6 weeks after ended treatment. INCLUSION CRITERIA: The patients will be recruited from the Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet. All of the following conditions must apply to the prospective patient at screening prior to receiving study agent: • A diagnosis of CVID based on ESID guidelines • 18 = and <75 years of age Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 50 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 6