Focal Segmental GlomerulosclerosisNCT04088799
LDL-Apheresis for FSGS CardioRenal Outcomes
An observational study of Focal Segmental Glomerulosclerosis, run by Children's Hospital Medical Center, Cincinnati at 2 sites in United States.
Trial summary
Focal segmental glomerulosclerosis (FSGS) is the most common cause of end-stage renal disease (ESRD) in adolescents. The refractory nature of FSGS and a more than 30% recurrence rate after kidney transplantation renders treatment of FSGS one of the most difficult challenges in pediatric nephrology. Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- Focal Segmental Glomerulosclerosis
- How many people
- 10 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Jan 2019to 1 Jun 2023
- Phase
- Observational
- 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 Up to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: Pediatric patients with focal segmental glomerulosclerosis (FSGS) in need of LDL-apheresis per standard of care
Who may be able to join
- FSGS and a glomerular filtration rate (GFR) ≥ 60 ml/min/1.73m2 AND
- Refractory nephrotic syndrome in which standard treatment options are unsuccessful (i.e., patient is unresponsive to standard corticosteroid and/or calcineurin inhibitor therapy for at least 8 weeks resulting in failure to achieve complete or partial remission), OR
- Refractory nephrotic syndrome in which standard treatment options are not well tolerated (i.e., patients intolerant to standard therapies due to severe side effects without providing an acceptable level of clinical benefit), OR
- Refractory or recurrent nephrotic syndrome in which standard therapy is contraindicated
- Post renal transplant with nephrotic syndrome associated with primary FSGS
Who cannot join
- Greater than 21 years of age
- Parent or patient unwilling or unable to signed and date the informed consent
- Pregnant, lactating, or planning to become pregnant prior to completing the study
- Unable or unwilling to comply with the follow-up schedule
- Simultaneously participating in another investigational drug or device study (except for LDL-apheresis associated trials)
- Body weight less than 21 kilograms (46 pounds)
Show all 15Show fewer
- Currently being administered angiotensin converting enzyme (ACE) inhibitors that cannot be withheld for at least 24 hours prior to each apheresis treatment
- Currently being administered antihypertensive drugs other than ACE inhibitors than cannot be withheld on the day of LDL-apheresis until after the procedure
- Medical condition or disorder that would limit life expectancy to less than the primary clinical study endpoint or that may cause noncompliance with the study plan or confound the data analysis
- Hypersensitivity to dextran sulfate, heparin, or ethylene oxide
- Inability to achieve adequate anticoagulation
- Inability to tolerate extracorporeal circulation therapy with Liposorber® LA-15
- Cardiac impairments such as uncontrolled arrhythmia, unstable angina, decompensated congestive heart failure, or valvular disease
- Thyroid disease or liver abnormalities
- Unresolved systemic or local infection that could affect the clinical study outcomes
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15224
About this study
Official title: Effect of LDL-Apheresis on Cardiovascular and Renal Outcomes in Focal Segmental Glomerulosclerosis (FSGS)
Focal segmental glomerulosclerosis (FSGS) is the most common cause of end-stage renal disease (ESRD) in adolescents. The refractory nature of FSGS and a more than 30% recurrence rate after kidney transplantation renders treatment of FSGS one of the most difficult challenges in pediatric nephrology. A significant knowledge gap in understanding the mechanism of FSGS treatment resistance and progression hampers development of successful treatment strategies. Beneficial effect of removal of low-density lipoproteins by LDL-apheresis indicates that lipids contribute to progression in FSGS.
The investigators will test the hypothesis that removal of Lp-PLA2 and lipid metabolites by LDL-apheresis ameliorates proteinuria and cardiovascular comorbidities. Patients with FSGS and FSGS recurrence after kidney transplantation receiving LDL-apheresis as part of standard of care will be enrolled to the study. Pre-and post serum and effluent concentrations of LPC, free FA, Lp-PLA2, oxidized LDL, fasting lipid profile, interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1β will be monitored in patients undergoing LDL-apheresis. Investigators will also study the impact of LDL-apheresis on cardiovascular and clinical comorbidities by monitoring degree of proteinuria, blood pressures and arterial stiffness index.
Read the detailed description
Focal segmental glomerulosclerosis (FSGS) is the most common cause of end-stage renal disease (ESRD) in adolescents. The refractory nature of FSGS and a more than 30% recurrence rate after kidney transplantation renders treatment of FSGS one of the most difficult challenges in pediatric nephrology. A significant knowledge gap in understanding the mechanism of FSGS treatment resistance and progression hampers development of successful treatment strategies. Beneficial effect of removal of low-density lipoproteins by LDL-apheresis indicates that lipids contribute to progression in FSGS. We have previously reported increased urinary fatty acids (FA) and lysophosphatidylcholines (LPC) levels with non-targeted urinary lipidomic analysis in children with FSGS. Unregulated phospholipase A2(PLA2) activity causes an increase in intracellular concentrations of free FA and LPC altering plasma membrane and mitochondrial permeability.
Lipoprotein associated PLA2 is a biomarker involved in oxidative modification of LDL by hydrolyzing oxidative lysophosphatidylcholines (LPC) and oxidized free fatty acids (FFA) both of which are proinflammatory and atherogenic. Lp-PLA2 is efficiently removed by LDL-apheresis. The investigators hypothesize that LDL-apheresis ameliorates cellular injury and vascular changes by removing circulating Lp-PLA2, oxidized LDL, LPC, FA and cytokines in FSGS. In this proposal, the hypothesis that removal of Lp-PLA2 and lipid metabolites by LDL-apheresis ameliorates proteinuria and cardiovascular comorbidities will be tested. Patients with FSGS and FSGS recurrence after kidney transplantation receiving LDL-apheresis as part of standard of care will be enrolled to the study. Investigators will monitor pre-and post serum and effluent concentrations of LPC, free FA, Lp-PLA2, oxidized LDL, fasting lipid profile, IL-6, TNF-α, and IL-1β of patients undergoing LDL-apheresis. The impact of LDL-apheresis on cardiovascular and clinical comorbidities by monitoring degree of proteinuria, blood pressures and arterial stiffness index will also be investigated.
The investigators propose that LDL-apheresis as a conjunct therapy to standard treatment regimens is an efficient way to ameliorate progression prevent comorbidities such as systemic inflammation and lipid induced vascular changes thus progression in FSGS. Furthermore, removal of Lp-PLA2 and other lipids by LDL-apheresis can limit the direct toxicity caused by lipid metabolites to podocytes and proximal tubule epithelial cells. The investigators believe that this proposal will enhance understanding of lipid-mediated progression in FSGS and will delineate the role of LDL-apheresis as part of established treatment in treatment of FSGS.
- Conditions
- Focal Segmental Glomerulosclerosis
- Being tested
- No intervention
- Medical subject headings
- Glomerulosclerosis, Focal Segmental
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
No interventionOther
No intervention
| Study group | Role | What they receive |
|---|---|---|
| FSGS requiring LDL-apheresis | Pediatric patients with FSGS requiring LDL-apheresis with the Liposorber Receives: Other: No intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Severity of Proteinuria
Standard of care proteinuria will be monitored for expected improvement in severity
Measured: 9 weeks
Secondary outcomes (1)
Cardiovascular comorbidities
LPC, free FA, Lp-PLA2, oxidized LDL, IL-6, TNF-α, and IL-1β will be monitored from patient blood before and after and from the effluent at LDL-apheresis treatments
Measured: 9 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Sep 2019
- Study start1 Jan 2019
- Primary completion1 Jun 2023
- Study completion1 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Focal Segmental GlomerulosclerosisStudies of the same condition, open and under way.
- More trials run by Children's Hospital Medical Center, CincinnatiThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital Medical Center, Cincinnati
- Sponsor type
- University, hospital or other
- Collaborators
- Kaneka Medical America LLC
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04088799
- Sponsor's protocol ID
- CIN001 - LDL Outcomes
- Status last verified
- Dec 2023
- First submitted
- 12 Sep 2019
- Last updated
- 21 Dec 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of LDL-Apheresis on Cardiovascular and Renal Outcomes in Focal Segmental Glomerulosclerosis (FSGS)
- ClinicalTrials.gov ID
- NCT04088799
- Acronym / sponsor ID
- CIN001 - LDL Outcomes
- Conditions
- Focal Segmental Glomerulosclerosis
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Children's Hospital Medical Center, CincinnatiUniversity, hospital or other
- Collaborators
- Kaneka Medical America LLC
- Study start
- 1 Jan 2019 (actual)
- Primary completion
- 1 Jun 2023 (actual)
- Study completion
- 1 Jun 2023 (actual)
- First posted
- 13 Sep 2019 (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.
Focal segmental glomerulosclerosis (FSGS) is the most common cause of end-stage renal disease (ESRD) in adolescents. The refractory nature of FSGS and a more than 30% recurrence rate after kidney transplantation renders treatment of FSGS one of the most difficult challenges in pediatric nephrology. A significant knowledge gap in understanding the mechanism of FSGS treatment resistance and progression hampers development of successful treatment strategies. Beneficial effect of removal of low-density lipoproteins by LDL-apheresis indicates that lipids contribute to progression in FSGS.
The investigators will test the hypothesis that removal of Lp-PLA2 and lipid metabolites by LDL-apheresis ameliorates proteinuria and cardiovascular comorbidities. Patients with FSGS and FSGS recurrence after kidney transplantation receiving LDL-apheresis as part of standard of care will be enrolled to the study. Pre-and post serum and effluent concentrations of LPC, free FA, Lp-PLA2, oxidized LDL, fasting lipid profile, interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1β will be monitored in patients undergoing LDL-apheresis. Investigators will also study the impact of LDL-apheresis on cardiovascular and clinical comorbidities by monitoring degree of proteinuria, blood pressures and arterial stiffness index.
Detailed description
Focal segmental glomerulosclerosis (FSGS) is the most common cause of end-stage renal disease (ESRD) in adolescents. The refractory nature of FSGS and a more than 30% recurrence rate after kidney transplantation renders treatment of FSGS one of the most difficult challenges in pediatric nephrology. A significant knowledge gap in understanding the mechanism of FSGS treatment resistance and progression hampers development of successful treatment strategies. Beneficial effect of removal of low-density lipoproteins by LDL-apheresis indicates that lipids contribute to progression in FSGS. We have previously reported increased urinary fatty acids (FA) and lysophosphatidylcholines (LPC) levels with non-targeted urinary lipidomic analysis in children with FSGS. Unregulated phospholipase A2(PLA2) activity causes an increase in intracellular concentrations of free FA and LPC altering plasma membrane and mitochondrial permeability.
Lipoprotein associated PLA2 is a biomarker involved in oxidative modification of LDL by hydrolyzing oxidative lysophosphatidylcholines (LPC) and oxidized free fatty acids (FFA) both of which are proinflammatory and atherogenic. Lp-PLA2 is efficiently removed by LDL-apheresis. The investigators hypothesize that LDL-apheresis ameliorates cellular injury and vascular changes by removing circulating Lp-PLA2, oxidized LDL, LPC, FA and cytokines in FSGS. In this proposal, the hypothesis that removal of Lp-PLA2 and lipid metabolites by LDL-apheresis ameliorates proteinuria and cardiovascular comorbidities will be tested. Patients with FSGS and FSGS recurrence after kidney transplantation receiving LDL-apheresis as part of standard of care will be enrolled to the study. Investigators will monitor pre-and post serum and effluent concentrations of LPC, free FA, Lp-PLA2, oxidized LDL, fasting lipid profile, IL-6, TNF-α, and IL-1β of patients undergoing LDL-apheresis. The impact of LDL-apheresis on cardiovascular and clinical comorbidities by monitoring degree of proteinuria, blood pressures and arterial stiffness index will also be investigated.
The investigators propose that LDL-apheresis as a conjunct therapy to standard treatment regimens is an efficient way to ameliorate progression prevent comorbidities such as systemic inflammation and lipid induced vascular changes thus progression in FSGS. Furthermore, removal of Lp-PLA2 and other lipids by LDL-apheresis can limit the direct toxicity caused by lipid metabolites to podocytes and proximal tubule epithelial cells. The investigators believe that this proposal will enhance understanding of lipid-mediated progression in FSGS and will delineate the role of LDL-apheresis as part of established treatment in treatment of FSGS.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| FSGS requiring LDL-apheresis | – | Other: No interventionPediatric patients with FSGS requiring LDL-apheresis with the Liposorber |
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- Pediatric patients with focal segmental glomerulosclerosis (FSGS) in need of LDL-apheresis per standard of care
Key inclusion criteria (5 listed)
- FSGS and a glomerular filtration rate (GFR) ≥ 60 ml/min/1.73m2 AND
- Post renal transplant with nephrotic syndrome associated with primary FSGS
Key exclusion criteria (15 listed)
- Greater than 21 years of age
- Parent or patient unwilling or unable to signed and date the informed consent
- Pregnant, lactating, or planning to become pregnant prior to completing the study
- Unable or unwilling to comply with the follow-up schedule
- Simultaneously participating in another investigational drug or device study (except for LDL-apheresis associated trials)
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 |
|---|---|---|
| No interventionNo intervention | Other | FSGS requiring LDL-apheresis |
Primary outcome
Severity of Proteinuria
Time frame: 9 weeks
Standard of care proteinuria will be monitored for expected improvement in severity
1 secondary outcome
Cardiovascular comorbidities
Time frame: 9 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Dec 2023.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Focal Segmental Glomerulosclerosis, run by Children's Hospital Medical Center, Cincinnati at 2 sites in United States.
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 5 inclusion and 15 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: finished, as of the sponsor's last update on 21 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. 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. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Severity of Proteinuria (time frame: 9 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 21 Dec 2023.