Efficacy and Safety of Super High-Flux Hemodialysis in Maintenance Dialysis Patients. SHINE-RLS (Super High-flux Dialysis Improves Neuro-symptoms and Efficacy in Restless Legs Syndrome) (SHINE-RLS)

August 27, 2026 updated by: Wan-Chuan Tsai, Far Eastern Memorial Hospital

Advancing Dialyzer Technology: Efficacy and Safety of Super High-Flux Hemodialysis in Maintenance Dialysis Patients

Patients with end-stage kidney disease (ESKD) rely on maintenance hemodialysis. While high-flux hemodialysis improves small solute clearance, its removal of middle-molecule uremic toxins (e.g., α1-microglobulin [α1-MG]) remains insufficient, contributing to symptoms such as restless legs syndrome (RLS), pruritus, and poor sleep quality, which are also linked to increased cardiovascular risk. In this study, the investigators evaluate whether using a "Super High-Flux" dialyzer (a Type V high-performance dialyzer) during hemodialysis can safely improve the removal of middle-molecule uremic toxins-specifically α1-microglobulin (α1-MG)-and relieve RLS symptoms in maintenance hemodialysis patients.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Patients with end-stage kidney disease (ESKD) on regular high-flux hemodialysis (HD) often experience an accumulation of middle-molecule uremic toxins, which are linked to systemic inflammation and troubling symptoms such as restless legs syndrome (RLS), severe itching, and poor sleep quality. While traditional high-flux dialysis efficiently clears small molecules, its ability to remove larger middle-molecule toxins (like α1-microglobulin [α1-MG]) is limited. Current alternatives such as online hemodiafiltration (HDF) have limitations, highlighting the need for new treatment approaches. Super High-Flux Hemodialysis (SHFHD) offers enhanced clearance of these middle molecules while preserving serum albumin levels and maintaining patient safety.

In this study, the investigators evaluate the effectiveness and safety of SHFHD compared with high-flux HD in patients undergoing maintenance HD, focusing on α1-MG removal and its potential effect on RLS. The investigators also explore the multiple diverse effects of SHFHD on the changes of cardiovascular risk factors including bone turnover, mineral metabolism, vascular calcification, uremia, inflammation, immunity, metabolomics, nutrition, and gut microbial metabolites in dialysis patients.

It is to conduct a randomized, controlled, crossover trial with cross-over design at a dialysis unit of tertiary teaching hospital in Northern Taiwan. The investigators will stratify participants by baseline RLS. Participants will receive either SHFHD or high-flux HD for 12 weeks, followed by a 4-week washout and crossover. The study outcome measures are difference in change-from-baseline values of α1-MG reduction ratio, RLS severity (International Restless Legs Scale), albumin levels, clearance of β2-microglobulin, free light chains, inflammatory markers, pruritus scores, and quality of life. Safety will be assessed via albumin maintenance, adverse events, and hemodynamic stability.

This will be the first RCT directly evaluating SHFHD for α1-MG removal and RLS outcomes, addressing critical knowledge gaps and potentially informing new dialysis prescription strategies.

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Wan-Chuan Tsai, M.D., Ph.D.
  • Phone Number: 1780 886-289667000
  • Email: mkks618@gmail.com

Study Locations

  • Taiwan
    • Banciao Dist.
      • New Taipei City, Banciao Dist., Taiwan, 220
        • Far Eastern Memorial Hospital
        • Contact:
          • Wan-Chuan Tsai, M.D., Ph.D.
          • Phone Number: 1780 886-277281780
          • Email: mkks618@gmail.com

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Diagnosis of Restless Legs Syndrome according to standard criteria.
  2. Age ≥ 20 years.
  3. Maintenance high-flux hemodialysis for ≥ 3 months.
  4. Stable vascular access (AV fistula or AV graft).
  5. Adequate dialysis delivery (URR ≥ 65% or Kt/V(daugirdes) ≥ 1.2).
  6. Sufficient iron stores (serum ferritin ≥ 200 ng/mL, TSAT ≥ 20%).
  7. Clinically stable condition for the past 4 weeks.
  8. Able and willing to comply with study protocol

Exclusion Criteria:

  1. Low-flux HD or temporary catheter use
  2. Serum albumin < 2.5 g/dL
  3. Recent hospitalization (within 4 weeks)
  4. Scheduled kidney transplantation
  5. Active malignancy or infection
  6. Pregnancy
  7. Any condition impairing protocol adherence

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Super High-Flux HD
Receives 12 weeks of Super High-Flux HD (Elisio™-HX)
Device: Super High-Flux HD
Participants receive hemodialysis using a Type V super high-flux dialyzer (such as Elisio™-HX or Theranova) for 12 weeks to assess the clearance of middle-molecule uremic toxins and its effect on RLS symptoms.
No Intervention: High-Flux HD
Receives 12 weeks of High-Flux HD as usual care

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from Baseline in α1-microglobulin (α1-MG) Reduction Ratio
Time Frame: Baseline, Week 4, Week 8, and Week 12 of each 12-week treatment period
The reduction ratio of α1-MG will be calculated as [({Pre-dialysis} - {Post-dialysis}) /{Pre-dialysis}] at each study visit. The primary outcome is the difference in the change-from-baseline reduction ratio between the Super High-Flux HD period and the High-Flux HD period.
Baseline, Week 4, Week 8, and Week 12 of each 12-week treatment period

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from Baseline in International Restless Legs Scale (IRLS) Score
Time Frame: Baseline, Week 4, Week 8, and Week 12 of each 12-week treatment period
IRLS score assesses the severity of Restless Legs Syndrome (ranging from 0 to 40, where higher scores indicate greater severity). Evaluated as the difference in score changes between the two treatment periods.
Baseline, Week 4, Week 8, and Week 12 of each 12-week treatment period
Change from Baseline in Pre-dialysis Serum Albumin Level
Time Frame: Baseline, Week 4, Week 8, and Week 12 of each 12-week treatment period
Monitored to evaluate nutritional safety and albumin preservation during Super High-Flux HD compared to High-Flux HD.
Baseline, Week 4, Week 8, and Week 12 of each 12-week treatment period
Change from Baseline in Pittsburgh Sleep Quality Index (PSQI) Score
Time Frame: Baseline, Week 4, Week 8, and Week 12 of each 12-week treatment period
Assesses sleep quality. Evaluated as the difference in score changes between the two treatment periods.
Baseline, Week 4, Week 8, and Week 12 of each 12-week treatment period
Change from Baseline in 5-D Itch Scale Score
Time Frame: Baseline, Week 4, Week 8, and Week 12 of each 12-week treatment period
Assesses pruritus severity. Evaluated as the difference in score changes between the two treatment periods.
Baseline, Week 4, Week 8, and Week 12 of each 12-week treatment period
Change from Baseline in health-related quality of life (EQ-5D-5L) Score
Time Frame: Baseline, Week 4, Week 8, and Week 12 of each 12-week treatment period
Assesses quality of life. Evaluated as the difference in score changes between the two treatment periods.
Baseline, Week 4, Week 8, and Week 12 of each 12-week treatment period
Change from Baseline in β2-microglobulin [β2-MG] Reduction ratio
Time Frame: Baseline, Week 4, Week 8, and Week 12 of each 12-week treatment period
The reduction ratio of β2-MG will be calculated as [({Pre-dialysis} - {Post-dialysis}) /{Pre-dialysis}] at each study visit and evaluated as the difference in the change-from-baseline reduction ratio between the Super High-Flux HD period and the High-Flux HD period.
Baseline, Week 4, Week 8, and Week 12 of each 12-week treatment period
Change from Baseline in Kappa Free Light Chains Reduction ratio
Time Frame: Baseline, Week 4, Week 8, and Week 12 of each 12-week treatment period
The reduction ratio will be calculated as [({Pre-dialysis} - {Post-dialysis}) /{Pre-dialysis}] at each study visit and evaluated as the difference in the change-from-baseline reduction ratio between the Super High-Flux HD period and the High-Flux HD period.
Baseline, Week 4, Week 8, and Week 12 of each 12-week treatment period
Change from Baseline in Lambda Free Light Chains Reduction ratio
Time Frame: Baseline, Week 4, Week 8, and Week 12 of each 12-week treatment period
The reduction ratio will be calculated as [({Pre-dialysis} - {Post-dialysis}) /{Pre-dialysis}] at each study visit and evaluated as the difference in the change-from-baseline reduction ratio between the Super High-Flux HD period and the High-Flux HD period.
Baseline, Week 4, Week 8, and Week 12 of each 12-week treatment period
Change from Baseline in Pre-dialysis Serum interleukin-6 (IL-6) Level
Time Frame: Baseline, Week 4, Week 8, and Week 12 of each 12-week treatment period
Measured at each study visit. Evaluated as the difference in the change from baseline between the Super High-Flux HD period and the High-Flux HD period.
Baseline, Week 4, Week 8, and Week 12 of each 12-week treatment period
Change from Baseline in Pre-dialysis Serum High-sensitivity C-reactive Protein (hs-CRP) Level
Time Frame: Baseline, Week 4, Week 8, and Week 12 of each 12-week treatment period
Measured at each study visit. Evaluated as the difference in the change from baseline between the Super High-Flux HD period and the High-Flux HD period.
Baseline, Week 4, Week 8, and Week 12 of each 12-week treatment period
Change from Baseline in Pre-dialysis Serum Indoxyl Sulfate Level
Time Frame: Baseline, Week 4, Week 8, and Week 12 of each 12-week treatment period
Measured at each study visit. Evaluated as the difference in the change from baseline between the Super High-Flux HD period and the High-Flux HD period.
Baseline, Week 4, Week 8, and Week 12 of each 12-week treatment period
Change from Baseline in Pre-dialysis Serum P-cresol Sulfate Level
Time Frame: Baseline, Week 4, Week 8, and Week 12 of each 12-week treatment period
Measured at each study visit. Evaluated as the difference in the change from baseline between the Super High-Flux HD period and the High-Flux HD period.
Baseline, Week 4, Week 8, and Week 12 of each 12-week treatment period

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Far Eastern Memorial Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

October 1, 2026

Primary Completion (Estimated)

September 30, 2027

Study Completion (Estimated)

September 30, 2029

Study Registration Dates

First Submitted

August 27, 2026

First Submitted That Met QC Criteria

August 27, 2026

First Posted (Actual)

August 31, 2026

Study Record Updates

Last Update Posted (Actual)

August 31, 2026

Last Update Submitted That Met QC Criteria

August 27, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FEMH-IRB-TSAI2025
  • FEMH-IIT-2026-01 (Other Grant/Funding Number: Far Eastern Memorial Hospital)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Individual-level deidentified participant data will be made available by the corresponding author of the paper upon request by email. The data will be available for 3 years after formal publication.

IPD Sharing Time Frame

The data will become available after completing the study for 1 year and for 3 years after formal publication.

IPD Sharing Access Criteria

Data will be made available by the corresponding author of the paper upon request by email.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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