Modulation of Vascular Calcification in Chronic Dialysis Patients

Study Overview
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Brief Summary
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50 patients will be randomized and treated with MCO or highflux dialysis for six months (24 weeks) after a run-in phase of 4 weeks Highflux treatment. Serum samples will be drawn at baseline, after 4, 8 and 24 weeks. Later, calcifiying vascular smooth muscle cells will be incubated with these serum samples and calcification will be assessed with Alkaline phosphatase and Alizarin staining. Primary endpoint: In vitro Calcification of coronary vascular smooth muscle cells (Alkaline Phosphatase/ WST8) after six months Calcifiying vascular smooth muscle cells will be incubated with serum samples obtained after six months of MCO/HF dialysis and calcification will be assessed with Alkaline phosphatase and WST8. Secondary Endpoints: Aortic Pulse wave velocity after 6 months Calcification propensity after 6 months Physical activity level after 6 months Cell culture: Incubation of VSMC with serum samples obtained after 6 months Alizarin staining/WST-8 Measurement of calcification inhibitors Osteopontin and Matrix Gla Protein in Supernatants Apoptosis The treatment regimen of the patients will not be altered, hence blood flow, dialysate flow as well as dialysis time will remain constant.

Official Title
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Modulation of Vascular Calcification in Chronic Dialysis Patients

Conditions
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Vascular Calcification

Intervention / Treatment
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* Device: Medium Cut-Off (MCO) dialysis membrane
* Device: High-Flux dialysis membrane


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years an older Chronic dialysis patients for at least 3 months Exclusion Criteria: Serum albumin <32g/L at the last routine albumin measurement Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MCO<br>Patients will be treated thrice weekly with Medium Cut-Off Dialysis membranes. | Device: Medium Cut-Off (MCO) dialysis membrane<br>* Patients will be treated with a CE-certified dialysis membrane that provide enhanced clearance for middle-sized molecules, call Medium Cut-Off membrane.<br>|
| Active Comparator: High-Flux<br>Patients will be treated thrice weekly with High-Flux Dialysis membranes. | Device: High-Flux dialysis membrane<br>* Control: Patients will be treated with a CE-certified High-Flux dialysis membrane.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| In vitro Calcification of coronary vascular smooth muscle cells (Alkaline Phosphatase/ WST8) after six months | Serum samples will be drawn at the beginning of the trial and after six months treatment with either High-Flux or Medium Cut-Off filters. Vascular smooth muscle cells will be incubated with thee serum samples and calcification will be assessed with Alkaline Phosphatase/ WST8 | Six months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Aortic Pulse wave velocity | Aortic Pulse wave velocity will be determined using the Vicorder Device. | Six months | 
| Calcification propensity | Calcification propensity will be determined as described earlier. (PMID: 24179171) | Six months | 
| Physical activity level | Physical activity level will be monitored for one week before and after treatment using an activity tracker. | Six months | 
| Cell culture: Incubation of VSMC with serum samples and assessment of • Alizarin staining/WST-8 • Measurement of calcification inhibitors Osteopontin and Matrix Gla Protein in Supernatants • Apoptosis | Additional in vitro calcification parameters will be assessed after incubation of VSMC with patient serum. | Six months |