E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Adult patients with the diagnosis of Common variable deficiency and fulfill the inclusion and exclusion criteria, will be invited to participate in the study. |
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E.1.1.1 | Medical condition in easily understood language |
Adult patients with the diagnosis of Common variable deficiency will be invited to participate in the study. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate if intervention with antibiotics (i.e. Rifaximin) modifies markers of systemic inflammation by alteration of the gut microbiota. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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
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E.4 | Principal 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 (e.g., cardiovascular disorders].
• Polypharmica with increased risk for interactions.
• Malignancy of any cause
• Impaired kidney function (i.e., estimated glomerulus filtration rate <50 ml/minute/1.73 m2]
• Alanine aminotransferase > 150 U/l or established liver cirrhoses.
• 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
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E.5 End points |
E.5.1 | 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)-1β, IL-6, IL-8 and IL-8], (iv) anti-inflammatory cytokines [e.g. IL-10, transforming growth factor β], (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],
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After Treatment: day 14 and 6 weeks after ended treatment. |
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E.5.2 | 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
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After Treatment day 14 and 6 weeks after ended treatment. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
An exploratory open-label randomized controlled trial |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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LVLS
The last visit of the last subject undergiong the trial, after the last 6 week follow-up |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |