Post Approval Study of Lixelle for the Treament of Dialysis-Related Amyloidosis

Description

Dialysis-related amyloidosis (DRA) is a serious complication of long-term hemodialysis (HD). Its pathogenic mechanism involves accumulation of β2-microglobulin (β2M) in the blood. β2M is produced by most cells in the body and is metabolized in the kidney in healthy individuals. However, in HD patients with renal dysfunction, β2M which is not removed entirely by HD accumulates excessively in the blood. Then it forms amyloid fibrils that are deposited in bones, joints, and soft tissues. The fibrils are further modified by advanced glycation end products (AGE), inducing local macrophage infiltration and production of cytokines leading to chronic inflammation and activation of osteoclasts. Consequently, severe complications with various symptoms are developed, which are collectively referred to as DRA. Lixelle® is a whole-blood β2M apheresis column developed to adsorb and eliminate β2M selectively from the blood of DRA patients. The treatment is performed with Lixelle® connected upstream of the dialyzer in series on a HD circuit in every session. The Lixelle® column contains porous cellulose beads with covalently linked hexadecyl alkyl chain ligands, which selectively adsorb β2M, via a molecular sieving effect because of its porous structure and hydrophobic interaction with ligands. Lixelle® has been used to relieve symptoms and prevent the progression of DRA in Japan since 1996, when health insurance coverage and reimbursement for the treatment were approved by Japanese Ministry of Health, Labor, and Welfare. Improvement of the activities of daily living (ADL) and remission of arthralgia by Lixelle® treatment has been shown in several clinical studies.

Conditions

Dialysis Amyloidosis

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Study Overview

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Study Details

Study overview

Dialysis-related amyloidosis (DRA) is a serious complication of long-term hemodialysis (HD). Its pathogenic mechanism involves accumulation of β2-microglobulin (β2M) in the blood. β2M is produced by most cells in the body and is metabolized in the kidney in healthy individuals. However, in HD patients with renal dysfunction, β2M which is not removed entirely by HD accumulates excessively in the blood. Then it forms amyloid fibrils that are deposited in bones, joints, and soft tissues. The fibrils are further modified by advanced glycation end products (AGE), inducing local macrophage infiltration and production of cytokines leading to chronic inflammation and activation of osteoclasts. Consequently, severe complications with various symptoms are developed, which are collectively referred to as DRA. Lixelle® is a whole-blood β2M apheresis column developed to adsorb and eliminate β2M selectively from the blood of DRA patients. The treatment is performed with Lixelle® connected upstream of the dialyzer in series on a HD circuit in every session. The Lixelle® column contains porous cellulose beads with covalently linked hexadecyl alkyl chain ligands, which selectively adsorb β2M, via a molecular sieving effect because of its porous structure and hydrophobic interaction with ligands. Lixelle® has been used to relieve symptoms and prevent the progression of DRA in Japan since 1996, when health insurance coverage and reimbursement for the treatment were approved by Japanese Ministry of Health, Labor, and Welfare. Improvement of the activities of daily living (ADL) and remission of arthralgia by Lixelle® treatment has been shown in several clinical studies.

Treatment of Dialysis-Related Amyloidosis Using Lixelle® β2-microglobulin Apheresis Column

Post Approval Study of Lixelle for the Treament of Dialysis-Related Amyloidosis

Condition
Dialysis Amyloidosis
Intervention / Treatment

-

Contacts and Locations

New York

The Rogosin Institute, New York, New York, United States, 10021

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.

For general information about clinical research, read Learn About Studies.

Eligibility Criteria

  • * Patients receiving thrice-weekly HD and diagnosed as DRA by one or more of the following 1 to 4 will be included.
  • 1. Biopsy of any tissue, showing Congo-red positive amyloid fibrils and immunohistochemical stains consistent with β2M
  • 2. Shoulder ultrasonography showing rotator cuffs greater than 8 mm in thickness, and /or echogenic pads between muscle groups of the rotator cuff
  • 3. Two or more diagnoses of the following (1) to (5) (1) Polyarthralgia (2) Carpal tunnel syndrome (3) Trigger finger (4) Dialysis-associated spondylosis ((i) or (ii)) (i) Destructive spondyloarthropathy (DSA) (ii) Spinal stenosis (5) Bone cysts (Bone cysts considered to be caused by other diseases such as osteoarthritis, aneurysmal bone cysts and unicameral bone cysts should be excluded.)
  • 4. Biopsy of any tissue, showing Congo-red positive amyloid fibrils, and one diagnosis or surgical history of criterion 3- (1) to (5)
  • * Patient who meets any of the following 1 to 7 will be excluded from the study.
  • 1. Patient diagnosed with rheumatoid arthritis
  • 2. Patient diagnosed with osteoporosis
  • 3. Patient diagnosed with osteoarthritis
  • 4. Patient planning to receive renal transplantation during the study
  • 5. Patient for whom adequate anticoagulation cannot be achieved
  • 6. Patient for whom extracorporeal circulation therapy is contraindicated, such as those with severe cardiac insufficiency, acute myocardial infarction, severe cardiac arrhythmia, acute seizure disorder, or severe uncontrolled hypertension or hypotension
  • 7. Patient planning to become pregnant, pregnant, or breast-feeding
  • 8. Patient unable to understand or answer the questionnaires even with a proper assistance

Ages Eligible for Study

to

Sexes Eligible for Study

ALL

Accepts Healthy Volunteers

No

Collaborators and Investigators

Kaneka Medical America LLC,

Jeffrey Silberzweig, MD, PRINCIPAL_INVESTIGATOR, The Rogosin Institute

Study Record Dates

2024-12