Uremic; ToxemiaNCT05755503
Toxicokinetics of Protein-bound Uremic Toxins in ESRD Patients
An observational study of Uremic; Toxemia and Pharmacokinetics, run by Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University at 1 site in China.
Trial summary
Protein-bound uremic toxins (PBUTs) are important uremic toxins, represented by indoxyl sulfate (IS), derived from the fermentation of dietary proteins by gut bacteria. The purpose of this study was to study the changes of IS in maintenance hemodialysis patients, and to construct a metabolic kinetics model of IS… Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Uremic; Toxemia, Pharmacokinetics, Renal Dialysis
- How many people
- 100 participants
- Where
- 1 siteChina
- Study dates
- 21 Feb 2023to 30 Dec 2025
- 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 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Uremia patients with maintenance hemodialysis in Shanghai ninth people's hospital
Who may be able to join
- Patients with maintenance hemodialysis were less than 85 years old and more than 18 years old, both male and female;
- Regular hemodialysis for more than 3 months, using arteriovenous fistula hemodialysis;
- Receiving high-throughput dialysis, HDF, and HP according to the conventional treatment regimen;
- Adequate dialysis (Kt/V>1.2 within one month);
- Keep your diet steady. Generally in good condition, have self-awareness, have a good understanding of their own illness and physical condition, and can communicate well with others;
- Understand and sign the informed consent
Who cannot join
- Patients with systemic or local severe infection;
- Patients with severe anemia: Hb<60g/L;
- Patients with hypoproteinemia: Alb<30g/L;
- Patients with insufficient daily protein intake: nPCR>1.0g/kg/d;
- Patients with malignant tumors;
- Patients with severe cardiovascular and cerebrovascular diseases, such as unstable angina pectoris, malignant hypertension, persistent atrial fibrillation, abnormal Q-wave of electrocardiogram, or patients with acute myocardial infarction, stroke, or coronary stent implantation within 3 months;
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- Patients with severe hematopoietic system diseases, such as aplastic anemia, globin aplastic anemia, thrombocytopenic purpura, etc.;
- Patients with severe digestive diseases, such as dysphagia, liver insufficiency, active gastrointestinal bleeding, intestinal obstruction, intestinal perforation, or previous subtotal gastrectomy, and other diseases that may affect digestion and absorption;
- Pregnant women;
- Participating in other clinical trials within one month or currently;
- Researchers consider it inappropriate.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University
Shanghai, Shanghai Municipality, 200011
Ding Feng, PhD, 0086-15802100898, dingfeng@sjtu.edu.cn
Wan Wenji, PhD
About this study
Protein-bound uremic toxins (PBUTs) are important uremic toxins, represented by indoxyl sulfate (IS), derived from the fermentation of dietary proteins by gut bacteria. The purpose of this study was to study the changes of IS in maintenance hemodialysis patients, and to construct a metabolic kinetics model of IS clearance. The model was then used to estimate the clearance rate of indoxyl sulfate by hemoperage, and to verify the application value of the model. This study intends to collect a series of serum, dialysate and urine samples from maintenance hemodialysis patients receiving high-throughput dialysis or hemodialysis filtration, so as to clarify the variation rule of IS during various blood purification treatments. Furthermore, a three-compartment model of dialysis IS metabolism kinetics was constructed according to the IS clearance of dialysis and residual kidney, and the above model was verified internally and externally. Finally, the model's fit and predictive value were validated in a group of MHD patients treated with HP without residual kidney.
Read the detailed description
The results of this study are helpful to clarify the rules of clearance and metabolism of PBUTs in hemodialysis patients, and lay a foundation for exploring effective means of blood purification and drugs to eliminate PBUTs, so as to reduce the incidence and mortality of complications in uremia patients.
Hemodialysis parameter setting: Blood flow 250ml/min, high throughput dialysis mode, dialysis process lasted for 4h
Samples collection time point:Blood samples: before hemodialysis, 1h, 2h, 4h after hemodialysis, 0.5h, 1h, 2h, 4h, 8h, 12h, 24h, 48h after hemodialysis.Dialysate samples: 1h, 1.5h, 2h, 3h, 4h after hemodialysis.Urine samples: 4h urine samples during hemodialysis.Hemoperfusion samples: before hemodialysis, 5min, 15min, 30min, 45min, 60min, 90min, 120min after hemodialysis.
The proposed model of IS toxicokinetics is a three-compartment model, in which the circulatory system is the central compartment, intertissue fluid is the fast equilibrium chamber, and cerebrospinal fluid, intracellular fluid, lymphatic fluid, etc. are the slow equilibrium chamber
- Conditions
- Uremic; Toxemia, Pharmacokinetics, Renal Dialysis
- Keywords
- Renal Dialysis, Uremic; Toxemia, Pharmacokinetics
- Medical subject headings
- Toxemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| IS modeling and validation group | Uremia patients receiving hemodialysis.This group was used to establish the IS three-compartment model and verify the accuracy and predictive value of the model |
What is being measured
The primary outcome is the main question the study is designed to answer.
The blood concentration of IS
The concentration of the free and protein-bound IS
Measured: From the beginning of dialysis to 48 hours after dialysis
The dialysate concentration of IS
The concentration of the free and protein-bound IS
Measured: Four hours of dialysis
The urine concentration of IS
The concentration of the free and protein-bound IS
Measured: Four hours of dialysis
Secondary outcomes (1)
Dialytic clearance
The total IS amount removed by dialysis
Measured: Four hours of dialysis
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2023
- Study start21 Feb 2023
- Primary completion30 Jun 2025 (estimated)
- Study completion30 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Uremic; ToxemiaStudies of the same condition, open and under way.
- More trials run by Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong UniversityThe 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
- Cross-sectional
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ding Feng, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University
- Investigators
- Ding Feng, PhD, Study director, Division of Nephrology,Shanghai Ninth People's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05755503
- Sponsor's protocol ID
- JYLJ202218
- Status last verified
- Apr 2024
- First submitted
- 2 Mar 2023
- Last updated
- 17 Apr 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Maheshwari V, Thijssen S, Tao X, Fuertinger D, Kappel F, Kotanko P. A novel mathematical model of protein-bound uremic toxin kinetics during hemodialysis. Sci Rep. 2017 Sep 4;7(1):10371. doi: 10.1038/s41598-017-10981-z.
PubMed 28871178Meyer TW, Peattie JW, Miller JD, Dinh DC, Recht NS, Walther JL, Hostetter TH. Increasing the clearance of protein-bound solutes by addition of a sorbent to the dialysate. J Am Soc Nephrol. 2007 Mar;18(3):868-74. doi: 10.1681/ASN.2006080863. Epub 2007 Jan 24.
PubMed 17251385Esquivias-Motta E, Martin-Malo A, Buendia P, Alvarez-Lara MA, Soriano S, Crespo R, Carracedo J, Ramirez R, Aljama P. Hemodiafiltration With Endogenous Reinfusion Improved Microinflammation and Endothelial Damage Compared With Online-Hemodiafiltration: A Hypothesis Generating Study. Artif Organs. 2017 Jan;41(1):88-98. doi: 10.1111/aor.12704. Epub 2016 May 16.
PubMed 27182679Devine E, Krieter DH, Ruth M, Jankovski J, Lemke HD. Binding affinity and capacity for the uremic toxin indoxyl sulfate. Toxins (Basel). 2014 Jan 24;6(2):416-29. doi: 10.3390/toxins6020416.
PubMed 24469432
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Toxicokinetics of Protein-bound Uremic Toxins in ESRD Patients
- ClinicalTrials.gov ID
- NCT05755503
- Acronym / sponsor ID
- JYLJ202218
- Conditions
- Uremic; Toxemia, Pharmacokinetics, Renal Dialysis
- Keywords
- Renal Dialysis, Uremic; Toxemia, Pharmacokinetics
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong UniversityUniversity, hospital or other
- Study start
- 21 Feb 2023 (actual)
- Primary completion
- 30 Jun 2025 (estimated)
- Study completion
- 30 Dec 2025 (estimated)
- First posted
- 6 Mar 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.
Protein-bound uremic toxins (PBUTs) are important uremic toxins, represented by indoxyl sulfate (IS), derived from the fermentation of dietary proteins by gut bacteria. The purpose of this study was to study the changes of IS in maintenance hemodialysis patients, and to construct a metabolic kinetics model of IS clearance. The model was then used to estimate the clearance rate of indoxyl sulfate by hemoperage, and to verify the application value of the model. This study intends to collect a series of serum, dialysate and urine samples from maintenance hemodialysis patients receiving high-throughput dialysis or hemodialysis filtration, so as to clarify the variation rule of IS during various blood purification treatments. Furthermore, a three-compartment model of dialysis IS metabolism kinetics was constructed according to the IS clearance of dialysis and residual kidney, and the above model was verified internally and externally. Finally, the model's fit and predictive value were validated in a group of MHD patients treated with HP without residual kidney.
Detailed description
The results of this study are helpful to clarify the rules of clearance and metabolism of PBUTs in hemodialysis patients, and lay a foundation for exploring effective means of blood purification and drugs to eliminate PBUTs, so as to reduce the incidence and mortality of complications in uremia patients.
Hemodialysis parameter setting: Blood flow 250ml/min, high throughput dialysis mode, dialysis process lasted for 4h
Samples collection time point:Blood samples: before hemodialysis, 1h, 2h, 4h after hemodialysis, 0.5h, 1h, 2h, 4h, 8h, 12h, 24h, 48h after hemodialysis.Dialysate samples: 1h, 1.5h, 2h, 3h, 4h after hemodialysis.Urine samples: 4h urine samples during hemodialysis.Hemoperfusion samples: before hemodialysis, 5min, 15min, 30min, 45min, 60min, 90min, 120min after hemodialysis.
The proposed model of IS toxicokinetics is a three-compartment model, in which the circulatory system is the central compartment, intertissue fluid is the fast equilibrium chamber, and cerebrospinal fluid, intracellular fluid, lymphatic fluid, etc. are the slow equilibrium chamber
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| IS modeling and validation group | – | –Uremia patients receiving hemodialysis.This group was used to establish the IS three-compartment model and verify the accuracy and predictive value of the model |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Uremia patients with maintenance hemodialysis in Shanghai ninth people's hospital
Key inclusion criteria (6 listed)
- Patients with maintenance hemodialysis were less than 85 years old and more than 18 years old, both male and female;
- Regular hemodialysis for more than 3 months, using arteriovenous fistula hemodialysis;
- Receiving high-throughput dialysis, HDF, and HP according to the conventional treatment regimen;
- Adequate dialysis (Kt/V>1.2 within one month);
- Keep your diet steady. Generally in good condition, have self-awareness, have a good understanding of their own illness and physical condition, and can communicate well with others;
Key exclusion criteria (11 listed)
- Patients with systemic or local severe infection;
- Patients with severe anemia: Hb<60g/L;
- Patients with hypoproteinemia: Alb<30g/L;
- Patients with insufficient daily protein intake: nPCR>1.0g/kg/d;
- Patients with malignant tumors;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
The blood concentration of IS
Time frame: From the beginning of dialysis to 48 hours after dialysis
The concentration of the free and protein-bound IS
The dialysate concentration of IS
Time frame: Four hours of dialysis
The concentration of the free and protein-bound IS
The urine concentration of IS
Time frame: Four hours of dialysis
The concentration of the free and protein-bound IS
1 secondary outcome
Dialytic clearance
Time frame: Four hours of dialysis
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2024.
- Background: PubMed 28871178Maheshwari V, Thijssen S, Tao X, Fuertinger D, Kappel F, Kotanko P. A novel mathematical model of protein-bound uremic toxin kinetics during hemodialysis. Sci Rep. 2017 Sep 4;7(1):10371. doi: 10.1038/s41598-017-10981-z.
- Background: PubMed 17251385Meyer TW, Peattie JW, Miller JD, Dinh DC, Recht NS, Walther JL, Hostetter TH. Increasing the clearance of protein-bound solutes by addition of a sorbent to the dialysate. J Am Soc Nephrol. 2007 Mar;18(3):868-74. doi: 10.1681/ASN.2006080863. Epub 2007 Jan 24.
- Background: PubMed 27182679Esquivias-Motta E, Martin-Malo A, Buendia P, Alvarez-Lara MA, Soriano S, Crespo R, Carracedo J, Ramirez R, Aljama P. Hemodiafiltration With Endogenous Reinfusion Improved Microinflammation and Endothelial Damage Compared With Online-Hemodiafiltration: A Hypothesis Generating Study. Artif Organs. 2017 Jan;41(1):88-98. doi: 10.1111/aor.12704. Epub 2016 May 16.
- Background: PubMed 24469432Devine E, Krieter DH, Ruth M, Jankovski J, Lemke HD. Binding affinity and capacity for the uremic toxin indoxyl sulfate. Toxins (Basel). 2014 Jan 24;6(2):416-29. doi: 10.3390/toxins6020416.
- 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.
Ding Feng, PhD study director
Division of Nephrology,Shanghai Ninth People's Hospital
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 Uremic; Toxemia and Pharmacokinetics, run by Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University at 1 site in China.
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 11 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: status not confirmed, as of the sponsor's last update on 17 Apr 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 China. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ding Feng, PhD (86-21-53315165, dingfeng@sjtu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The blood concentration of IS (time frame: From the beginning of dialysis to 48 hours after dialysis). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05755503, which also lists 4 linked publications.
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 17 Apr 2024.