HemodialysisVALLOIRENCT05373524
Rheopheresis Mechanism in Hemodialysis Patients With PAD
A study testing Biological analysis in people with Hemodialysis, run by University Hospital, Grenoble at 1 site in France.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hemodialysis
- What is being tested?
- Biological analysis
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 18 participants
- Where
- 1 siteFrance
- Study dates
- Jun 2022to May 2024
- Phase
- Interventional
- 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
Who may be able to join
- 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
Who cannot join
- - 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
Trial locations and contacts
1 site in 1 country.
France1 site
Grenoble University Hospital
Grenoble, 38043
Hamza Naciri Bennani, MD, +33476765460, hnaciribennani@chu-grenoble.fr
Lionel ROSTAING, MD, PhD
About this study
Official title: Rheopheresis Mechanism of Action and Impacts on the Evolution of Peripheral Arterial Disease in Hemodialysis Patients
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.
Read more
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.
Read the detailed 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.
- Conditions
- Hemodialysis
- Being tested
- Biological analysis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biological analysisBiological
Rheopheresis using plasma separation and plasma filtration, coupled to hemodialysis
| Study group | Role | What they receive |
|---|---|---|
| the rheopheresis group | Active comparator | Rheopheresis is performed using an automated monitor in a double-filtration cascade. Plasma purify from of high molecular weight proteins through a secondary filter is then returned to the patient. This technique is performed in tandem with a hemodialysis monitor. Receives: Biological: Biological analysis |
| the shamapheresis group | Placebo comparator | Shamapheresis is performed with the same automated monitor (Plasauto, HemaT company). Extracted plasma is not treated through the secondary filter (Rheofilter) and return to the patient. This technique is performed in tandem with a hemodialysis monitor. Receives: Biological: Biological analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Blood viscosity measured by rotational rheometer
To assess the effect of rheopheresis on blood viscosity of chronic hemodialysis patients with PAD
Measured: Immediately before 1ST and immediately after 12th procedure , outcome measurement will be reported at the end of the study (approximately 3 years)
Secondary outcomes (1)
Blood viscosity measured by rotational rheometer
Evaluate the effect of rheopheresis on blood viscosity measured by rotational rheometer before the 12th treatment session
Measured: up to 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2022
- Study startJun 2022 (estimated)
- Primary completionMay 2024 (estimated)
- Study completionMay 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for HemodialysisStudies of the same condition, open and under way.
- More trials run by University Hospital, GrenobleThe 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Rheopheresis procedure/Shamapheresis procedure
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Grenoble
- Sponsor type
- University, hospital or other
- Collaborators
- University Grenoble Alps
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05373524
- Sponsor's protocol ID
- 38RC20.461
- Acronym
- VALLOIRE
- Status last verified
- May 2022
- First submitted
- 18 Jan 2022
- Last updated
- 13 May 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 23791036Meyer 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):822-829.e1. doi: 10.1016/j.jvs.2017.12.048. Epub 2018 Mar 26.
PubMed 29598891Lowry 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 10.
PubMed 27390224Weiss 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.
PubMed 22175277Ferrannini 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. doi: 10.1177/039139880703001010.
PubMed 17992654Klingel R, Mumme C, Fassbender T, Himmelsbach F, Altes U, Lotz J, Pohlmann T, Beyer J, Kustner 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. doi: 10.1046/j.1526-0968.2003.00082.x.
PubMed 12887730Kirschkamp T, Schmid-Schonbein 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):360-7. doi: 10.1111/j.1744-9987.2008.00610.x.
PubMed 18937718Briers JD. Laser Doppler, speckle and related techniques for blood perfusion mapping and imaging. Physiol Meas. 2001 Nov;22(4):R35-66. doi: 10.1088/0967-3334/22/4/201.
PubMed 11761081Roustit 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.
PubMed 20542492Choi 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. doi: 10.1117/1.2341196.
PubMed 16965157Stewart 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. doi: 10.1016/j.burns.2005.04.004.
PubMed 16129229
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Rheopheresis Mechanism of Action and Impacts on the Evolution of Peripheral Arterial Disease in Hemodialysis Patients
- ClinicalTrials.gov ID
- NCT05373524
- Acronym / sponsor ID
- VALLOIRE / 38RC20.461
- Conditions
- Hemodialysis
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- University Hospital, GrenobleUniversity, hospital or other
- Collaborators
- University Grenoble Alps
- Study start
- Jun 2022 (estimated)
- Primary completion
- May 2024 (estimated)
- Study completion
- May 2024 (estimated)
- First posted
- 13 May 2022 (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.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 2
- Model description
- Rheopheresis procedure/Shamapheresis procedure
| Arm | Type | Receives |
|---|---|---|
| the rheopheresis group | Active comparator | Biological: Biological analysisRheopheresis is performed using an automated monitor in a double-filtration cascade. Plasma purify from of high molecular weight proteins through a secondary filter is then returned to the patient. This technique is performed in tandem with a hemodialysis monitor. |
| the shamapheresis group | Placebo comparator | Biological: Biological analysisShamapheresis is performed with the same automated monitor (Plasauto, HemaT company). Extracted plasma is not treated through the secondary filter (Rheofilter) and return to the patient. This technique is performed in tandem with a hemodialysis monitor. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (5 listed)
- - 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
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 |
|---|---|---|
| Biological analysisRheopheresis using plasma separation and plasma filtration, coupled to hemodialysis | Biological | the rheopheresis group, the shamapheresis group |
Primary outcome
Change in Blood viscosity measured by rotational rheometer
Time frame: Immediately before 1ST and immediately after 12th procedure , outcome measurement will be reported at the end of the study (approximately 3 years)
To assess the effect of rheopheresis on blood viscosity of chronic hemodialysis patients with PAD
1 secondary outcome
Blood viscosity measured by rotational rheometer
Time frame: up to 24 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2022.
- Background: PubMed 23791036Roustit 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.
- Results publication: PubMed 29598891Meyer 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):822-829.e1. doi: 10.1016/j.jvs.2017.12.048. Epub 2018 Mar 26.
- Results publication: PubMed 27390224Lowry 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 10.
- Results publication: PubMed 22175277Weiss 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.
- Results publication: PubMed 17992654Ferrannini 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. doi: 10.1177/039139880703001010.
- Results publication: PubMed 12887730Klingel R, Mumme C, Fassbender T, Himmelsbach F, Altes U, Lotz J, Pohlmann T, Beyer J, Kustner 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. doi: 10.1046/j.1526-0968.2003.00082.x.
- Results publication: PubMed 18937718Kirschkamp T, Schmid-Schonbein 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):360-7. doi: 10.1111/j.1744-9987.2008.00610.x.
- Results publication: PubMed 11761081Briers JD. Laser Doppler, speckle and related techniques for blood perfusion mapping and imaging. Physiol Meas. 2001 Nov;22(4):R35-66. doi: 10.1088/0967-3334/22/4/201.
- Results publication: PubMed 20542492Roustit 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.
- Results publication: PubMed 16965157Choi 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. doi: 10.1117/1.2341196.
- Results publication: PubMed 16129229Stewart 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. doi: 10.1016/j.burns.2005.04.004.
- 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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Biological analysis in people with Hemodialysis, run by University Hospital, Grenoble at 1 site in France.
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 5 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 13 May 2022. 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 France. 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. Some participants in this study may receive a placebo. 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 HAMZA MD NACIRI BENNANI (33476765460, HNaciribennani@chu-grenoble.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Blood viscosity measured by rotational rheometer (time frame: Immediately before 1ST and immediately after 12th procedure , outcome measurement will be reported at the end of the study (approximately 3 years)). 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 NCT05373524, which also lists 11 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 13 May 2022.