Post Approval Study of Lixelle for the Treament of Dialysis-Related Amyloidosis
ConditionDialysis Amyloidosis
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
AgeNot listed
SponsorKaneka Medical America LLC
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Patients receiving thrice-weekly HD and diagnosed as DRA by one or more of the following 1 to 4 will be included.
Biopsy of any tissue, showing Congo-red positive amyloid fibrils and immunohistochemical stains consistent with β2M
Shoulder ultrasonography showing rotator cuffs greater than 8 mm in thickness, and /or echogenic pads between muscle groups of the rotator cuff
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.)
Disqualifiers
Patient who meets any of the following 1 to 7 will be excluded from the study.
Patient diagnosed with rheumatoid arthritis
Patient diagnosed with osteoporosis
Patient diagnosed with osteoarthritis
Trial design
Design model
Parallel
Treatments tested in this trial
Lixelle® treatment
DeviceThe treatment will be performed with the Lixelle® column connected to upstream of the dialyzer in series on the routine HD circuit according to the description in the IFU. The dialyzer and the Kt/V urea in the conventional HD for each patient will be kept equal in Lixelle®-treatment. Since the maximum blood flow rate for Lixelle® is 250 ml/min, the dialysis time will be extended to achieve the target Kt/V urea. The study will not restrict the type of hemodialyzer and other conditions of HD as specified by the physician. However, any changes to the HD procedure should be recorded properly, and the Kt/V urea should be kept equal to that at the enrollment.
Treatment groups
40 Participants
are divided into 2 treatment groupsGroup A: Lixelle® treatmentExperimental treatment 1 intervention
Group B: natural historyNo intervention 0 interventions
Trial outcomes
Primary outcomes
1
the rate of SAE
comparison of incidence of SAE between between the Lixelle® treatment group and the natural history during treatment period (2 years)
Time frame
through 2 years of Lixelle® treatment during the study periodSecondary outcomes
1
β2M reduction rate in Lixelle® treatment (2 year)
to compare how much blood β2M level have decreased after after Lixelle® treatment against pre-treatment level.
Time frame
comparison between baseline and 2 years (104 weeks) after Lixelle® treatment2
comparison of β2M reduction rate between Lixelle® treatment and natural history
to compare β2M reduction rate (see Description in Outcome 2) between the Lixelle® treatment grroup and tne natural history group.
Time frame
comparison between baseline and 2 years (104 weeks) after Lixelle® treatmentSponsors and contacts
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Source ClinicalTrials.gov