Rheopheresis Mechanism in Hemodialysis Patients With PAD

Hemodialysis Clinical Trial

— VALLOIRE  

Official title:

Rheopheresis Mechanism of Action and Impacts on the Evolution of Peripheral Arterial Disease in Hemodialysis Patients

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05373524
• Other study ID #: 38RC20.461
• Status: Not yet recruiting
• Phase: N/A
• Start date: June 2022
• Est. completion date: May 2024

Study information

• Verified date: May 2022
• Source: University Hospital, Grenoble
• Contact: HAMZA MD NACIRI BENNANI
• Phone: 33476765460
• Email: HNaciribennani[@]chu-grenoble.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Peripheral arterial disease (PAD) is common in chronic hemodialysis patients (HDC) with a prevalence of 30% according to the DOPPS study. The combination of PAD and chronic kidney disease (CKD) stage 5 is a risk factor for major amputation (24.5%) with a mortality rate of 55% at 2 years. Ischemia occurring during PAD is the result of impaired microcirculation, with insufficient blood flow to maintain tissue perfusion and viability. It is responsible for painful skin wounds whose healing is poor, with a significant risk of infection. In patients with chronic renal failure, it is linked to both: - local phenomena (atherosclerosis, calcification) - changes in blood viscosity (elevated hematocrit and inflammatory proteins, especially fibrinogen) - a neovascularization defect (uremic toxins, in particular indoxyl sulphate). If revascularization is not possible, amputation remains the only possible treatment to relieve pain and limit the risk of infection. Rheopheresis is an apheresis technique that allows the depletion of high molecular weight serum proteins. This would reduce blood viscosity and red blood cell (RBC) aggregation, thereby improving microvascular perfusion, with the aim of reducing pain, improving healing and limiting the risk of amputation. Several studies have investigated the efficacy of rheopheresis in PAD in HDC, but the level of evidence remains low.

Description:

The main objective of our study is to evaluate the impact of rheopheresis on blood (main objective) and plasma viscosity, skin microcirculation and blood coagulation (Fibrinography, Thrombin Generation). No study has evaluated the direct effect of rheopheresis on these different parameters. However, a better understanding of these mechanisms would make it possible both to optimize the effectiveness of the technique, to limit its potential side effects and the cost of treatment.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 18
• Est. completion date: May 2024
• Est. primary completion date: May 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age 18 years or more and included in the RHEOPAD protocol (2019-A01513-54)
• ESRD treated by hemodialysis or hemodiafiltration
• PAD-LTI with tissue loss and/or wounds (ulcers or gangrene) with at least one of the following criterion, subject to the feasibility of the measures: arterial pressure assessment at the ankle <70 mmHg, or toe pressure 30 mm Hg, or transcutaneous oximetry measurements < 40 mm Hg
• Interventional or surgical revascularization either not technically possible or no necessary
• Medical insurance
• Signed informed consent

Exclusion Criteria:

• - Uncontrolled infection despite well-conducted antibiotic therapy
• Life expectancy < 1 year
• Severe cognitive or psychiatric disorders
• Pregnant woman, parturient, nursing mother
• Patients unable to give an informed consent or unwilling to participate in the study

Related Conditions & MeSH terms

• Hemodialysis

Intervention

Biological:
• Biological analysis
Rheopheresis using plasma separation and plasma filtration, coupled to hemodialysis

Locations

Country	Name	City	State
France	Grenoble University Hospital	Grenoble

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Grenoble	University Grenoble Alps

Country where clinical trial is conducted

France, 

References & Publications (11)

Briers JD. Laser Doppler, speckle and related techniques for blood perfusion mapping and imaging. Physiol Meas. 2001 Nov;22(4):R35-66. Review. — View Citation

Choi B, Ramirez-San-Juan JC, Lotfi J, Stuart Nelson J. Linear response range characterization and in vivo application of laser speckle imaging of blood flow dynamics. J Biomed Opt. 2006 Jul-Aug;11(4):041129. — View Citation

Ferrannini M, Vischini G, Staffolani E, Scaccia F, Miani N, Parravano MC, Louis MM, Splendiani G, Di Daniele N. Rheopheresis in vascular diseases. Int J Artif Organs. 2007 Oct;30(10):923-9. — View Citation

Kirschkamp T, Schmid-Schönbein H, Weinberger A, Smeets R. Effects of fibrinogen and alpha2-macroglobulin and their apheretic elimination on general blood rheology and rheological characteristics of red blood cell aggregates. Ther Apher Dial. 2008 Oct;12(5 — View Citation

Klingel R, Mumme C, Fassbender T, Himmelsbach F, Altes U, Lotz J, Pohlmann T, Beyer J, Küstner E. Rheopheresis in patients with ischemic diabetic foot syndrome: results of an open label prospective pilot trial. Ther Apher Dial. 2003 Aug;7(4):444-55. — View Citation

Lowry D, Saeed M, Narendran P, Tiwari A. The Difference Between the Healing and the Nonhealing Diabetic Foot Ulcer: A Review of the Role of the Microcirculation. J Diabetes Sci Technol. 2017 Sep;11(5):914-923. doi: 10.1177/1932296816658054. Epub 2016 Jul — View Citation

Meyer A, Fiessler C, Stavroulakis K, Torsello G, Bisdas T, Lang W; CRITISCH collaborators. Outcomes of dialysis patients with critical limb ischemia after revascularization compared with patients with normal renal function. J Vasc Surg. 2018 Sep;68(3):822 — View Citation

Roustit M, Cracowski JL. Assessment of endothelial and neurovascular function in human skin microcirculation. Trends Pharmacol Sci. 2013 Jul;34(7):373-84. doi: 10.1016/j.tips.2013.05.007. Epub 2013 Jun 21. Review. — View Citation

Roustit M, Millet C, Blaise S, Dufournet B, Cracowski JL. Excellent reproducibility of laser speckle contrast imaging to assess skin microvascular reactivity. Microvasc Res. 2010 Dec;80(3):505-11. doi: 10.1016/j.mvr.2010.05.012. Epub 2010 Jun 9. — View Citation

Stewart CJ, Frank R, Forrester KR, Tulip J, Lindsay R, Bray RC. A comparison of two laser-based methods for determination of burn scar perfusion: laser Doppler versus laser speckle imaging. Burns. 2005 Sep;31(6):744-52. — View Citation

Weiss N. A critical review on the use of lipid apheresis and rheopheresis for treatment of peripheral arterial disease and the diabetic foot syndrome. Semin Dial. 2012 Mar-Apr;25(2):220-7. doi: 10.1111/j.1525-139X.2011.01036.x. Epub 2011 Dec 16. Review. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Evaluate the effect of rheopheresis on plasma viscosity measured by falling ball viscometer	Plasma viscosity measured by falling ball viscometer in pre vs post session 1 and in pre session 12 vs baseline.	Immediately before day 0 and 12-th procedure and immediately after 1st procedure
Other	Evaluate the effect of rheopheresis on skin microvascular function (1st and 12th sessions pre and post session)	Post-occlusive and thermal hyperaemia of cutaneous blood flow measured by speckle contrast imaging, compared between the rheopheresis and shamapheresis groups (1st and 12th sessions pre and post session)	Immediately before day0 and 1 years
Other	Evaluate the effect of rheopheresis on coagulation	Study of the lifespan of the blood clot (difference between formation time and clot lysis time) using a multi-well plate spectrophotometer (Fibrinography);	Immediately before day 0 and 12-th procedure and immediately after 1st procedure
Primary	Change in Blood viscosity measured by rotational rheometer	To assess the effect of rheopheresis on blood viscosity of chronic hemodialysis patients with PAD	Immediately before 1ST and immediately after 12th procedure , outcome measurement will be reported at the end of the study (approximately 3 years)
Secondary	Blood viscosity measured by rotational rheometer	Evaluate the effect of rheopheresis on blood viscosity measured by rotational rheometer before the 12th treatment session	up to 24 weeks