Effects of High Cut-off (HCO) Hemodialysis on Central Memory CD4+ T and Treg Cells in Patients With End-stage Kidney Disease

NCT01103076 | Unknown Phase 2 DMC

• 2 other identifiers: HighCO Hemo studyHCO study
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

In this study, the investigators will evaluate whether CD4+ TCM producing effector cytokines can be distinguished on the basis of their expression of the IL-7 receptor alpha-chain (CD127). Using CD154 production as a marker of Ag-specific CD4+ T cells, the investigators will also test the hypothesis that the phenotype and function of TCM are influenced by the type of Ag they recognize. TCM specific for two cleared protein Ag, tetanus toxoïd (TT) and hepatitis B surface (HBs), inducing an early stage of CD4+ T cell differentiation will be compared to TCM specific for cytomegalovirus (CMV), a persistent virus inducing an advanced stage of CD4+ T cell differentiation. The primary endpoint is to demonstrate in uremic patients who will begin chronic HD and in patients already chronically hemodialyzed any improvement in CD4+ T cell function ex vivo and in vitro. These analyzes will focus on memory T-cell subsets (i.e. Th17 and Tregs population) using HCO membranes or polyamide dialyzers. The secondary endpoint is a clinical one, namely, to show any improvement in T cell response to HB and TT vaccination (blood antibody titers).

Conditions

End-stage Kidney Disease; CD4 T Cells; Central Memory T Cells; Regulatory T Cells; Uremic Toxins

Keywords

Immune dysfunction; Hemodialysis; HBV; Vaccination; Immune response

Outcome Measures

Primary Outcomes (1)

• HCO 1100 membrane effect on T CM and Tregs in patients with ESKD chronically hemodialzed

  The primary endpoint is to demonstrate in uremic patients who will begin chronic HD and in patients already chronically hemodilyzed any improvement in CD4+ T cell function ex vivo and in vitro. These analyzes will focus on memory T-cell subsets (i.e. Th17 and Tregs population) using HCO membranes or polyamide dialyzers.

  12 HD sessions

Secondary Outcomes (1)

• Immunogenicity of the HB-AS04 vaccine in patients dialyzed with HCO 1100 or polyamide membranes

  12 months study

Study Arms (2)

Polyamide 210 H

ACTIVE COMPARATOR

Chronic HD patients will be treated in random order with either polyamide or HCO membranes (Polyflux 210 H or HCO 1100) for one month (12 HD sessions) before the crossover.

Device: Polyamide HD membrane

HCO 1100

EXPERIMENTAL

Chronic HD patients will be treated in random order with either polyamide or HCO membranes (Polyflux 210 H or HCO 1100) for one month (12 HD sessions) before the crossover.

Device: Polyamide HD membrane

Interventions

Polyamide HD membrane DEVICE

Single use polyamide membrane

HCO 1100; Polyamide 210 H

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with ESKD (CKD stage 5D according to K/DOQI guidelines) regularly treated by bicarbonate HD 3 times a week for at least 4 h at a blood flow rate of 300 ml/min will be included

You may not qualify if:

• Only non-smokers will be enrolled in the study
• Patients with recent (\< 3 mo) major trauma, surgery, myocardial infarction, coronary revascularization (coronary angioplasty or bypass surgery), or stroke will be excluded from the study
• Diabetes mellitus
• The presence of an acute or chronic inflammatory process, infection
• Malnutrition (determined by Subjective Global Nutritional Assessment)
• The use of immunosuppressive drugs or evidence of malignancy
• Pregnant women, women who are breast feeding or are of child-bearing potential and not using adequate contraceptive precautions are excluded
• Except for aspirin and statin, those patients taking anti-inflammatory medications in the prior 4 weeks will be excluded.
• All patients have to be negative for circulating hepatitis B antigen, hepatitis C antibody (Ab) and HIV
• They will have no active liver disease
• No patient will be nephrectomized
• Arterial blood pH will be between 7.38 and 7.42
• No patient will receive a blood transfusion in the 6 mo before the study

Sponsors & Collaborators

• Centre Hospitalier du Centre du Valais: lead
• Research Unit CHCVs Hôpital de Sion Switzerland: collaborator
• Immunology ICHV Sion Switzerland: collaborator
• University of Lausanne Hospitals: collaborator

Study Sites (1)

Hôpital de Sion CHCVs

Sion, Valais, 1951, Switzerland

RECRUITING

Related Publications (2)

• Meier P, Golshayan D, Blanc E, Pascual M, Burnier M. Oxidized LDL modulates apoptosis of regulatory T cells in patients with ESRD. J Am Soc Nephrol. 2009 Jun;20(6):1368-84. doi: 10.1681/ASN.2008070734. Epub 2009 Apr 30.

  PMID: 19406979 BACKGROUND

• Meier P, Spertini F, Blanc E, Burnier M. Oxidized low-density lipoproteins activate CD4+ T cell apoptosis in patients with end-stage renal disease through Fas engagement. J Am Soc Nephrol. 2007 Jan;18(1):331-42. doi: 10.1681/ASN.2006050514. Epub 2006 Dec 20.

  PMID: 17182885 BACKGROUND

Related Links

• Centre Hospitalier Universitaire Vaudois
• Université de Lausanne

MeSH Terms

Conditions

Kidney Failure, Chronic; Immune System Diseases

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Pascal Meier, MD

  Nephrology service CHCVs Hôpital de Sion/Switzerland

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Pascal Meier, MD

CONTACT

+41276034000; pascal.meier@hopitalvs.ch

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: April 13, 2010
• First Posted: April 14, 2010
• Study Start: April 1, 2011
• Primary Completion: December 1, 2011
• Study Completion: February 1, 2012
• Last Updated: July 7, 2011

Record last verified: 2010-03

Locations

CH (1)