End-stage Kidney DiseaseNCT05957146
Kinetics of Extracellular Vesicles in Hemodialysis
An observational study of End-stage Kidney Disease, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
Trial summary
The aim of this observational study is to gain insight into the kinetics of extracellular vesicles (EVs), derived from both in- (i.e. bio-incompatibility) and outside (tissue-injury) the extracorporeal circuit (ECC), during standard hemodialysis (HD) in adult prevalent end-stage kidney disease (ESKD) patients treated… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- End-stage Kidney Disease
- What is being tested?
- Routine hemodialysis
- Type of treatment
- Medical device
- How many people
- 6 participants
- Where
- 1 siteNetherlands
- Study dates
- 7 Nov 2023to 9 Feb 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Adults patients treated with chronic intermittent hemodialysis (3x per week during 4 hours) during at least 3 months
Who may be able to join
- Age >18 years
- Stable clinical situation: free of infection, no recent admission
- HD >3 months
- Haemoglobin level >6,2 mmol/L
- Residual diuresis <200mL/24h
- Willing and able to give written informed consent.
Who cannot join
- Active infection, malignancy, auto-immune disease, or treatment with immunosuppressive medication.
- Allergy to polysulfone dialysers
- Life expectancy <3 months due to non-renal disease
- Access recirculation
Trial locations and contacts
1 site in 1 country.
About this study
The aim of this observational study is to gain insight into the kinetics of extracellular vesicles (EVs), derived from both in- (i.e. bio-incompatibility) and outside (tissue-injury) the extracorporeal circuit (ECC), during standard hemodialysis (HD) in adult prevalent end-stage kidney disease (ESKD) patients treated with HD.
During a single HD session, blood samples for EV-assessment will be taken at several time points and at different sampling sites in the extracorporeal circuit (sampling point 1: before the rollerpump, arterial line; sampling point 2: after the rollerpump and before the dialyzer, sampling point 3: after the dialyzer, efferent line).
Read the detailed description
Hemodialysis (HD) is a lifesaving treatment for ESKD patients. Yet, apart from beneficial effects, HD has adverse consequences, which, apart from rapid osmolality and electrolyte shifts, results from the bio-incompatibility (BI) of the extra-corporeal circuit (ECC) and intradialytic hypotension (IDH) as well. While BI arises within the ECC due to the contact between circulating blood cells and the foreign materials of the lines and dialyzer, IDH-induced tissue injury (TI) originates within the body of the patients. Activated cells can be detected by upregulation of cell surface markers and release of degradation products. Substances which are smaller than the pores of dialyzer-membranes may pass this barrier and, thus, become undetectable in blood.
Various cell types shed small particles upon activation an/or injury, so called extracellular vesicles (EVs). These EVs, which are shed by various cell types upon activation and/or injury, contain various proteins and are too large to travers dialyzer membranes. Their assessment requires strict and standardized collection and handling of blood samples. In previous HD research, both pre-analytical circumstances and analytic methods were insufficiently standardized, precluding solid conclusions. Both the contact between circulating blood cells and the ECC, and recurrent IDH, predispose to micro-inflammation and cell activation, which are related to morbidity and mortality. Hence, when analysed properly, the measuring of EVs might be a valuable tool to assess dialysis-induced adverse side-effects, not only in the dialyzer but also in the body, which, when occurring repeatedly, may influence survival.
In a recent study, we found an increase in EVs during treatment with different dialysis modalities. However, EVs were only assessed before and after dialysis. Hence, in the present study, we aim to assess the kinetics of EVs in routine HD.
- Conditions
- End-stage Kidney Disease
- Being tested
- Routine hemodialysis
- Keywords
- Hemodialysis, Extracellular vesicles, Bio-incompatibility, Tissue injury
- Medical subject headings
- Kidney Failure, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Routine hemodialysisDevice
- Dialyzers: Cordiax FX80 dialyzers; membrane material HelixonePlus (polysulfone); (Fresenius Medical Care Bad Homburg, Germany)
- Dialysis machines: Baxter Gambro AK 98 (Gambro Lundia AB, Lund, Sweden; part of Baxter Healthcare Corporation)
- Needles for vascular access: Nipro SafeTouch dialysis cath 1.6x25 mm (16G) or 1.9x25 mm (15G); or Nipro SafeTouch Tulip needles (15G; all Nipro Medical Europe Mechelen, Belgium)
- Ultrapure dialysis fluids (less than 0.1 colony forming units/ml, less than 0.03 endotoxin units/ml) will be mixed with AC-F 219/1 or 213/4 liquid acid concentrates and BiBag dry bicarbonate concentrate. Hence, the electrolyte composition of the dialysis fluid will be: Na 138-142 mmol/L; K 2.0-3.0 mmol/L; HCO3 26-35 mmol/L; Ca 1.25-1.50 mmol/L; Mg 0.5 mmol/L; Cl 108.5-109 mmol/L; glucose 5.6 mmol/L; acetate 3 mmol/L. Dialysate flow rate will be 500 mL/min.
- Anticoagulation: nadroparin.
| Study group | Role | What they receive |
|---|---|---|
| Chronic hemodialysis patients | Adult patients treated with routine hemodialysis 3x/week during at least 3 months Receives: Device: Routine hemodialysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Intradialytic change in the concentration of extracellular vesicles from specific cell types
Blood cell-derived EVs: platelets: CD61+, activated platelets: CD61+/CD62p+; erythrocytes: CD235a+; leukocytes CD45+; and endothelium-derived EVs: CD144+, activated endothelium CD62e+; myocardium and endothelium-derived: Connexin-43+ will be measured at different sampling sites (sampling point 1: before the roller pump, arterial line; sampling point 2: after the rollerpump and before the dialyzer, sampling point 3: after the dialyzer, efferent line).
Measured: 4 hours (=one dialysis treatment); assessed at the following time points: 0 minutes (start of dialysis), 30 min, 60 min, 120 min, 180 min, 235 minutes
Secondary outcomes (5)
Intradialytic blood pressure
Change in systolic and diastolic blood pressure (mmHg) during dialysis
Measured: 4 hours (=one dialysis treatment); measured 4x/hour
Hematocrit (Ht)
the volume percentage of red blood cells (RBCs) in blood
Measured: 4 hours (=one dialysis treatment); measured three times (at the start (0 minutes), half way (120 minutes) and at the end (240 minutes))
High sensitive CRP (hsCRP)
Marker of inflammation
Measured: 4 hours (=one dialysis treatment); measured once at the start of dialysis (0 minutes)
White blood cell (WBC) count
Total white blood cell count and differential count
Measured: 4 hours (=one dialysis treatment); measured once at the start of dialysis (0 minutes)
Platelet count
Number of platelets in blood
Measured: 4 hours (=one dialysis treatment); measured once at the start of dialysis (0 minutes)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2023
- Study start7 Nov 2023
- Primary completion9 Feb 2024
- Study completion9 Feb 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for End-stage Kidney DiseaseStudies of the same condition, open and under way.
- More trials run by Amsterdam UMC, location VUmcThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amsterdam UMC, location VUmc
- Sponsor type
- University, hospital or other
- Collaborators
- Dianet Dialysis Centers
- Responsible party
- Principal investigator, Muriel P.C. Grooteman, Amsterdam UMC, location VUmc
- Investigators
- Muriel PC Grooteman, MD PhD, Principal investigator, VUmc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05957146
- Sponsor's protocol ID
- NL84115.018.23
- Status last verified
- Oct 2024
- First submitted
- 4 Jul 2023
- Last updated
- 3 Oct 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Kinetics of Extracellular Vesicles in Hemodialysis
- ClinicalTrials.gov ID
- NCT05957146
- Acronym / sponsor ID
- NL84115.018.23
- Conditions
- End-stage Kidney Disease
- Keywords
- Hemodialysis, Extracellular vesicles, Bio-incompatibility, Tissue injury
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Amsterdam UMC, location VUmcUniversity, hospital or other
- Collaborators
- Dianet Dialysis Centers
- Study start
- 7 Nov 2023 (actual)
- Primary completion
- 9 Feb 2024 (actual)
- Study completion
- 9 Feb 2024 (actual)
- First posted
- 24 Jul 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of this observational study is to gain insight into the kinetics of extracellular vesicles (EVs), derived from both in- (i.e. bio-incompatibility) and outside (tissue-injury) the extracorporeal circuit (ECC), during standard hemodialysis (HD) in adult prevalent end-stage kidney disease (ESKD) patients treated with HD.
During a single HD session, blood samples for EV-assessment will be taken at several time points and at different sampling sites in the extracorporeal circuit (sampling point 1: before the rollerpump, arterial line; sampling point 2: after the rollerpump and before the dialyzer, sampling point 3: after the dialyzer, efferent line).
Detailed description
Hemodialysis (HD) is a lifesaving treatment for ESKD patients. Yet, apart from beneficial effects, HD has adverse consequences, which, apart from rapid osmolality and electrolyte shifts, results from the bio-incompatibility (BI) of the extra-corporeal circuit (ECC) and intradialytic hypotension (IDH) as well. While BI arises within the ECC due to the contact between circulating blood cells and the foreign materials of the lines and dialyzer, IDH-induced tissue injury (TI) originates within the body of the patients. Activated cells can be detected by upregulation of cell surface markers and release of degradation products. Substances which are smaller than the pores of dialyzer-membranes may pass this barrier and, thus, become undetectable in blood.
Various cell types shed small particles upon activation an/or injury, so called extracellular vesicles (EVs). These EVs, which are shed by various cell types upon activation and/or injury, contain various proteins and are too large to travers dialyzer membranes. Their assessment requires strict and standardized collection and handling of blood samples. In previous HD research, both pre-analytical circumstances and analytic methods were insufficiently standardized, precluding solid conclusions. Both the contact between circulating blood cells and the ECC, and recurrent IDH, predispose to micro-inflammation and cell activation, which are related to morbidity and mortality. Hence, when analysed properly, the measuring of EVs might be a valuable tool to assess dialysis-induced adverse side-effects, not only in the dialyzer but also in the body, which, when occurring repeatedly, may influence survival.
In a recent study, we found an increase in EVs during treatment with different dialysis modalities. However, EVs were only assessed before and after dialysis. Hence, in the present study, we aim to assess the kinetics of EVs in routine HD.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Chronic hemodialysis patients | – | Device: Routine hemodialysisAdult patients treated with routine hemodialysis 3x/week during at least 3 months |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Adults patients treated with chronic intermittent hemodialysis (3x per week during 4 hours) during at least 3 months
Key inclusion criteria (6 listed)
- Age >18 years
- Stable clinical situation: free of infection, no recent admission
- HD >3 months
- Haemoglobin level >6,2 mmol/L
- Residual diuresis <200mL/24h
Key exclusion criteria (4 listed)
- Active infection, malignancy, auto-immune disease, or treatment with immunosuppressive medication.
- Allergy to polysulfone dialysers
- Life expectancy <3 months due to non-renal disease
- Access recirculation
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Routine hemodialysis* Dialyzers: Cordiax FX80 dialyzers; membrane material HelixonePlus (polysulfone); (Fresenius Medical Care Bad Homburg, Germany) * Dialysis machines: Baxter Gambro AK 98 (Gambro Lundia AB, Lund, Sweden; part of Baxter Healthcare Corporation) * Needles for vascular access: Nipro SafeTouch dialysis cath 1.6x25 mm (16G) or 1.9x25 mm (15G); or Nipro SafeTouch Tulip needles (15G; all Nipro Medical Europe Mechelen, Belgium) * Ultrapure dialysis fluids (less than 0.1 colony forming units/ml, less than 0.03 endotoxin units/ml) will be mixed with AC-F 219/1 or 213/4 liquid acid concentrates and BiBag dry bicarbonate concentrate. Hence, the electrolyte composition of the dialysis fluid will be: Na 138-142 mmol/L; K 2.0-3.0 mmol/L; HCO3 26-35 mmol/L; Ca 1.25-1.50 mmol/L; Mg 0.5 mmol/L; Cl 108.5-109 mmol/L; glucose 5.6 mmol/L; acetate 3 mmol/L. Dialysate flow rate will be 500 mL/min. * Anticoagulation: nadroparin. | Device | Chronic hemodialysis patients |
Primary outcome
Intradialytic change in the concentration of extracellular vesicles from specific cell types
Time frame: 4 hours (=one dialysis treatment); assessed at the following time points: 0 minutes (start of dialysis), 30 min, 60 min, 120 min, 180 min, 235 minutes
Blood cell-derived EVs: platelets: CD61+, activated platelets: CD61+/CD62p+; erythrocytes: CD235a+; leukocytes CD45+; and endothelium-derived EVs: CD144+, activated endothelium CD62e+; myocardium and endothelium-derived: Connexin-43+ will be measured at different sampling sites (sampling point 1: before the roller pump, arterial line; sampling point 2: after the rollerpump and before the dialyzer, sampling point 3: after the dialyzer, efferent line).
5 secondary outcomes
Intradialytic blood pressure
Time frame: 4 hours (=one dialysis treatment); measured 4x/hour
Hematocrit (Ht)
Time frame: 4 hours (=one dialysis treatment); measured three times (at the start (0 minutes), half way (120 minutes) and at the end (240 minutes))
High sensitive CRP (hsCRP)
Time frame: 4 hours (=one dialysis treatment); measured once at the start of dialysis (0 minutes)
White blood cell (WBC) count
Time frame: 4 hours (=one dialysis treatment); measured once at the start of dialysis (0 minutes)
Platelet count
Time frame: 4 hours (=one dialysis treatment); measured once at the start of dialysis (0 minutes)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Oct 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Muriel PC Grooteman, MD PhD principal investigator
VUmc
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of End-stage Kidney Disease, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Intradialytic change in the concentration of extracellular vesicles from specific cell types (time frame: 4 hours (=one dialysis treatment); assessed at the following time points: 0 minutes (start of dialysis), 30 min, 60 min, 120 min, 180 min, 235 minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Oct 2024.