Reduction of Oxalate and Inflammation by Hemodiafiltration vs. Hemodialysis

• ClinicalTrials.gov Identifier: NCT02684656
• Recruitment Status: Completed
• First Posted: February 18, 2016
• Last Update Posted: December 24, 2019
• Sponsor: University of Erlangen-Nürnberg Medical School
• Collaborator: Renal Research Institute
• Information provided by (Responsible Party): University of Erlangen-Nürnberg Medical School

Tracking Information

• First Submitted Date: February 9, 2016
• First Posted Date: February 18, 2016
• Last Update Posted Date: December 24, 2019
• Actual Study Start Date: February 2016
• Actual Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: February 12, 2016): Plasma oxalate [ Time Frame: 6 months ]
• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures (submitted: February 12, 2016): Cytokines measured by multiplex analysis [ Time Frame: 6 months ]
• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Reduction of Oxalate and Inflammation by Hemodiafiltration vs. Hemodialysis
• Official Title: Pilot Study of Lowering Plasma Oxalate With Hemodiafiltration to Reduce Systemic Inflammation in Patients With End-Stage Renal Disease (ESRD)
• Brief Summary: The health care burden of CKD is substantial and growing with 10-15% of the population affected in both developed and developing countries. It is well established that CKD is associated with systemic inflammation, which promotes cardiovascular disease and body wasting. However, causal therapies to treat systemic inflammation, and treat its adverse consequences remain sparse. As kidney function declines in all forms of CKD, oxalate levels increase in the plasma, leading to increased systemic exposure to oxalate and consequent tissue injury. Work from the investigators has shown that elevated plasma oxalate levels activate the NLRP3 inflammasome which in turn leads to the processing and release of cytokines. The investigators seek to test the hypothesis that oxalate contributes to the systemic inflammation observed in patients with end-stage renal disease (ESRD). The investigators plan to define the association between plasma oxalate levels and signs of systemic inflammation in patients on hemodialysis. In a second step the investigators will examine whether hemodiafiltration lowers plasma oxalate more efficiently than hemodialysis and reduces signs of systemic inflammation. Confirmation of the hypothesis may lead to the identification of oxalate as a novel therapeutic target for interventional trials aimed at reducing plasma oxalate in patients with ESRD.
• Detailed Description: The positive interaction between diffusive and convective flux has suggested that hemodiafiltration (HDF) has a higher oxalate extraction rate as compared with hemodialysis (HD). However, it has not been evaluated whether HDF can lower predialysis oxalate levels below the level of supersaturation. By using an intra-individual approach with the inclusion/exclusion criteria listed for the study, we plan to determine plasma oxalate and cytokine levels in 20 patients (10 on regular duration HD, 10 patients on extended duration HD) before dialysis. Subsequently, patients will be switched to HDF and plasma oxalate concentration and cytokines will be analyzed again two weeks following HDF treatment. Plasma oxalate (Pox) will be measured at beginning of treatment, mid, end and 2 hrs post treatment (to determine rebound) in order to provide oxalate kinetics on HD/HDF treatment. Cytokines will only be measured pre HD/HDF treatment to assess steady state inflammation.
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Non-Randomized; Intervention Model: Crossover Assignment; Masking: None (Open Label); Primary Purpose: Diagnostic
• Condition: Chronic Kidney Disease Requiring Chronic Dialysis

Intervention

• Procedure: Hemodialysis
  Hemodialysis >/=4h
• Procedure: Hemodiafiltration
  Hemodiafiltration >/=4h, > 20l convection

Study Arms

• Active Comparator: Hemodialysis
  Intervention: Patients will be switch to hemodialysis and basal plasma oxalate levels as well as oxalate removal by hemodialysis will be determined after two weeks of treatment.
  Intervention: Procedure: Hemodialysis
• Active Comparator: Hemodiafiltration
  Intervention: Patients will be switch back to hemodiafiltration and basal plasma oxalate levels as well as oxalate removal by hemodiafiltration will be determined after two weeks of treatment.
  Intervention: Procedure: Hemodiafiltration

Publications *

• Hoppe B, Kemper MJ, Bökenkamp A, Portale AA, Cohn RA, Langman CB. Plasma calcium oxalate supersaturation in children with primary hyperoxaluria and end-stage renal failure. Kidney Int. 1999 Jul;56(1):268-74.
• Knauf F, Asplin JR, Granja I, Schmidt IM, Moeckel GW, David RJ, Flavell RA, Aronson PS. NALP3-mediated inflammation is a principal cause of progressive renal failure in oxalate nephropathy. Kidney Int. 2013 Nov;84(5):895-901. doi: 10.1038/ki.2013.207. Epub 2013 Jun 5.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 20, 2019): 14
• Original Estimated Enrollment (submitted: February 12, 2016): 20
• Actual Study Completion Date: September 2016
• Actual Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Blood Flow ≥ 250 ml/min
• Dialysate Flow ≥ 500 ml/min
• Urinary Excretion < 400 ml/24h
• Duration of Dialysis ≥ 4h
• On HDF/HD treatment for ≥ 4 weeks
• Extended HDF/HD for ≥ 4 weeks

Exclusion Criteria:

• Recirculation (online measurement) > 15%
• Single needle dialysis or single lumen catheter
• Substitution volume of < 20l on HDF

Sex/Gender

• Sexes Eligible for Study: All

• Ages: Child, Adult, Older Adult
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Germany

Administrative Information

• NCT Number: NCT02684656
• Other Study ID Numbers: UErlangen-Nurnberg
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: University of Erlangen-Nürnberg Medical School
• Study Sponsor: University of Erlangen-Nürnberg Medical School
• Collaborators: Renal Research Institute

Investigators

• Principal Investigator: Felix Knauf, MD; University Erlangen-Nuremberg, Germany
• Principal Investigator: Kai-Uwe Eckardt, MD; University Erlangen-Nuremberg, Germany
• Principal Investigator: Fred Finkelstein, MD; Medical Director of New Haven Home Dialysis
• Principal Investigator: Peter S Aronson, MD; Yale University New Haven, USA
• Principal Investigator: Chirag Parikh, MD; Yale University New Haven
• Principal Investigator: Mark A Perazella, MD; Yale University New Haven

• PRS Account: University of Erlangen-Nürnberg Medical School
• Verification Date: December 2019