Outcome
Type |
Measure |
Description |
Time frame |
Safety issue |
Other |
Change in concentration of microbial uremic toxins in the blood; hippuric acid, kynurenic acid, indoxyl sulfate and p-cresol sulfate |
Biomarkers will include markers of bacterial uremic toxins (hippuric acid, kynurenic acid, indoxyl sulfate and p-cresol sulfate). |
30 weeks. Blood tests will be performed before and after each of the two treatment periods. |
|
Other |
Change in Gut microbiome characterization assessed by 16S RNA sequencing |
Fecal samples will be collected at visit 2, 3, 4 and 5 for calprotectin and gut microbiome analyses. Feces is collected according to current standard operation procedures in order to characterize the gut microbiome. The fecal samples should be stored at -20 °C in the participants' freezer and be delivered to SDCC in the provided cooling bag no more than 48 hours after collection. At SDCC the samples will be stored at -80°C. The gut microbiome characterization is based on 16S rRNA gene sequencing. After standardized microbial DNA extraction, the microbial DNA will be subjected to sequencing, microbial gene analyses, taxonomy analyses including enterotypes known species and unknown meta-species and functional annotation. |
30 weeks. Fecal samples will be collected before and after each of the two treatment periods. |
|
Primary |
Change in albuminuria based on urinary albumin-creatinine ratio (UACR) |
Three morning urine samples will be collected for assessment of UACR. The geometric mean of the 3 samples will be calculated. |
30 weeks. Samples will be collected before and after each og te two treatment periods. |
|
Secondary |
Change in kidney function (GFR as plasma clearance of 99mTc-DTPA) |
Renal function (GFR) and extracellular volume (ECV) will be assessed during 4 hours with the measurement plasma clearance of 99mTc-DTPA to provide accurate GFR measurement. A bolus of 0.5 mL Technetium-99m DTPA (approximately 10 MBq) is injected and blood samples are drawn at 0, 180, 200, 220 and 240 minutes after the injection. Urine is collected during the investigation. Plasma concentrations of 99mTc-DTPA at these time points are measured and used to calculate the plasma clearance of 99mTc-DTPA which approximates GFR. |
30 weeks. 99mTc-DTPA GFR will be performed after each of the two treatment periods. |
|
Secondary |
Change in 24-hour blood pressure |
24-hours blood pressure will be measured using a standard cuff-based device (boso TM-2430 PC2) that measures the blood pressure every 15 minutes between 07 in the morning and 23 in the evening and every 30 minutes during the night. |
30 weeks. 24h BP will be performed after each of the two treatment periods. |
|
Secondary |
Change in microcirculation evaluated by the GlycoCheck device |
GlycoCheck is a handheld video capillary microscope that measure glycocalyx thickness and sublingual capillary density under the tongue. The measurement will be performed by investigator and is a measure of the microcirculation damage. The distribution of the red blood cell column width at each capillary segment is used to calculate the perfused boundary region, which is the distance between the median and the outer edge of the red blood cell perfused lumen. The perfused boundary region reflects the thickness of the endothelial glycocalyx, based on the idea that loss of its integrity allows deeper penetration of the red blood cells into the gel-like layer covering the endothelial lining. Higher perfused boundary region, therefore, indicates thinner glycocalyx. The software also returns total and perfused capillary density in segments per millimeter square. |
30 weeks. GlycoCheck will be performed before and after each of the two treatment periods. |
|
Secondary |
Change in endothelial dysfunction (von Willebrand factor, endothelin-1, ADMA, ICAM-1, VCAM-1 and E-selectin) |
Biomarkers drawn from blood will include markers of endothelial dysfunction (von Willebrand factor, endothelin-1, ADMA, ICAM-1, VCAM-1 and E-selectin), |
30 weeks. Blood tests will be performed before and after each of the two treatment periods. |
|
Secondary |
Change in urinary markers of oxidative stress F2-isoprostanes and 8-oxodG |
Markers of oxidative stress (F2-isoprostanes and 8-oxodG) will be measured in urine by ELISA and multiplexing methods. |
30 weeks. Urine samples will be collected before and after each of the two treatment periods. |
|
Secondary |
Change in intestinal inflammation measured by fecal calprotectin |
Fecal samples will be collected for calprotectin analyses. |
30 weeks. Fecal samples will be collected before and after each of the two treatment periods. |
|
Secondary |
Change in biomarkers of intestinal permeability (LPS and zonulin) |
Biomarkers drawn from blood will include markers of intestinal permeability (LPS and zonulin) |
30 weeks. Blood tests will be performed before and after each of the two treatment periods. |
|
Secondary |
Change in systemic inflammation (hs-TNT, TNF-alfa, IL6, IL8, IL1-beta, SAA, sICAM1, sICAM3 and suPAR) |
Biomarkers drawn from blood will include markers of inflammation (hs-TNT, TNF-alfa, IL6, IL8, IL1-beta, SAA, sICAM1, sICAM3, suPAR) |
30 weeks. Blood tests will be performed before and after each of the two treatment periods. |
|
Secondary |
Change in tubular function (NGAL, KIM-1, Beta2microglobulin, hepatocellular growth factor and adiponectin) |
Markers of tubular kidney injury (NGAL, KIM-1, Beta2microglobulin, hepatocellular growth factor (HGF) and adiponectin) will be measured in urine by ELISA and multiplexing methods. |
30 weeks. Urine samples will be collected before and after each of the two treatment periods. |
|
Secondary |
Change in autonomous neuropathy evaluated by VagusTM |
Autonomic nervous system function will be evaluated with the VagusTM device. The heart rate will be measured by 5-minute resting measures and in response to deep breathing, position change from lying to standing position and by exhaling through a mouthpiece against 40 mmHg of pressure (Valsalva maneuver). |
30 weeks. Vagus test will be performed before and after each of the two treatment periods. |
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