The Rifaximin Study in CVID

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

Patients with Common variable immunodeficiency (CVID) have various forms of autoimmune and auto inflammatory disorders. The study will investigate if intervention with Rifaximin modifies the gut microbiota with a subsequent alteration in markers of systemic immune activation and inflammation in patients with CVID. The investigators hypothesize that the gut microbiota of CVID patients, at least partly through interaction with the innate immune system within the intestine, contribute to a low-grade systemic inflammation in these patients, and that an intervention with the non-absorbable antibiotic Rifaximin attenuates systemic inflammation through modulation of the gut microbiota. The study may lead to increased understanding of the interaction between microbiota and the immune system. The study could give new insight into important disease processes in relation to the interaction between the microbiota, the intestine and the systemic compartment, and potentially be the basis of new therapeutic strategies in these patients to prevent and down-regulate the auto-inflammatory and autoimmune complications seen in CVID. The findings could also be of relevance for other disorders where the interaction between microbiota and intestinal and systemic inflammation is involved such as various cardiovascular and metabolic disorders.

The investigators hypothesize that the gut microbiota of CVID patients, at least partly through interaction with the innate immune system within the intestine, contribute to a low-grade systemic inflammation in these patients, and that an intervention with the non-absorbable antibiotic Rifaximin attenuates systemic inflammation through modulation of the gut microbiota.

Study Overview

• Status: Completed
• Conditions: Common Variable Immunodeficiency (CVID)
• Intervention / Treatment: Drug: Rifaximin

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 4

Contacts and Locations

Study Locations

• Norway
  • Oslo, Norway
    • Oslo University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 74 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18 ≥ and <75 years of age
• A diagnosis of CVID: decreased serum levels (> 2 SD) of immunoglobulin (Ig)G, IgA and/or IgM and exclusion of other forms of hypogammaglobulinemia

Exclusion Criteria:

• Previous treatment with antibiotics within the last 12 weeks
• History of hypersensitivity to Rifaximin or other Rifamycin derived antimicrobial agents, or any of the components of XIFAXAN
• Comorbidity not related to CVID- i.e. conditions or symptoms that may influence with the patient safety or compromise the study results (e.g., cardiovascular disorders, alcoholism, psychiatric disease, HIV infection etc.)].
• Polypharmacy with increased risk for interactions. i.e. patient with an extensive medication lists (e.g. 10 drugs or more) this may influence with the patient safety or compromise the study results
• Malignancy of any cause
• Impaired kidney function (i.e., estimated glomerulus filtration rate <50 ml/minute/1.73 m2]
• Impaired liver function (Alanine aminotransferase > 150 U/l) or established liver cirrhosis.
• Pregnant or planning to be pregnant in the study period to avoid interference of pregnancy with gut microbiota (not because of toxicity].
• Nursing
• On-going infection, including GI infection
• The use of probiotics for the recent 6 months
• Any immunosuppressive drugs,

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: No treatment; patient receive no active treatment
Experimental: Rifaximin; Patient takes Rifaximin 550mg twice daily for 14 days	Drug: Rifaximin; Other Names: Xifaxan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in inflammatory and anti-inflammatory mediators	Changes in serum/plasma/whole blood of tumor necrosis factor alpha (TNF-alpha), c reactive protein (CRP), soluble CD14 and other cytokines/chemokines.	after 2 and 8 weeks after Day 0

Collaborators and Investigators

• Sponsor: Oslo University Hospital
• Investigators: Principal Investigator: Borre Fevang, MD, Phd, Oslo University Hospital

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: September 12, 2013
• First Submitted That Met QC Criteria: September 17, 2013
• First Posted (Estimate): September 20, 2013

Study Record Updates

• Last Update Posted (Estimate): April 24, 2015
• Last Update Submitted That Met QC Criteria: April 23, 2015
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Immunologic Deficiency Syndromes; Common Variable Immunodeficiency; Anti-Infective Agents; Gastrointestinal Agents; Anti-Bacterial Agents; Rifaximin
• Other Study ID Numbers: 2013/1037; 2013-000883-27 (EudraCT Number); 13/09446-7 (Other Identifier: The Norwegian Medicines Agency)