Nephrotic SyndromePhase 1OxLDLNCT01845428
Lipid Lowering Agents to Limit Lipid Oxidation and Activation of Clotting System in Nephrotic Syndrome
A Phase 1 study testing Pravastatin in people with Nephrotic Syndrome and Hyperlipidemia, run by University of North Carolina, Chapel Hill at 1 site in United States.
Trial summary
The purpose of this research study is to learn if using statin in patients with nephrotic syndrome could lower the risk of blood clots. Nephrotic syndrome is a collection of signs and symptoms that occur when the glomeruli -the tiny filters that work in the kidney- leak protein in the urine. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Nephrotic Syndrome, Hyperlipidemia
- What is being tested?
- Pravastatin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- May 2012to Jan 2017
- Phase
- Phase 1
- 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 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Inclusion Criteria:• Prevalent or incident patients of either sex, ages 18-70, with Membranous Nephropathy (MN) , Focal Segmental GlomeruloSclerosis (FSGS), or Minimal Change Disease (MCD).
- Proteinuria ≥ 3.0 g/day by 24hr urine collection or urine protein/creatinine ratio ≥ 2.
- Hyperlipidemia as defined by fasting or direct LDL ≥ 150 mg/dl. -
Exclusion Criteria:Inability or unwillingness to comply with the study protocol and follow-up visits.
Patients unable to provide written consent will be excluded.
-
Trial locations and contacts
1 site in 1 country.
United States1 site
Unc Kidney Center
Chapel Hill, North Carolina, 27599-7155
About this study
Official title: Assessment of the Efficacy of Lipid-lowering Agents to Limit Lipid Oxidation and Activation of the Clotting System in Patients With the Nephrotic Syndrome: a Pilot Study.
The purpose of this research study is to learn if using statin in patients with nephrotic syndrome could lower the risk of blood clots. Nephrotic syndrome is a collection of signs and symptoms that occur when the glomeruli -the tiny filters that work in the kidney- leak protein in the urine.
One of the symptoms associated with nephrotic syndrome is hyperlipidemia: too much bad cholesterol (LDL). This bad cholesterol could be linked to the increased risk of blood clots in patients with nephrotic syndrome. The study doctors would like to see if taking a statin drug to reduce the amount of bad cholesterol could reduce the risk of blood clots.
Read the detailed description
Venous thromboembolic (VTE) events are common in the nephrotic syndrome (NS) occurring in up to 30% of patients when systematically screened. The investigator proposes to explore a novel mechanism for the increased clot formation in NS. To date, the only consistently identified underlying risk factor for VTEs is severe hypoalbuminemia related to the NS. The underlying pathophysiology related to VTE in NS remains poorly understood and has previously been ascribed to dysregulation of pro- and anticoagulant clotting factors due to urinary protein losses and reflected by the low serum albumin. However, the direct evidence for this mechanism is inconsistent and relatively poor. Another feature of NS is that of severe hyperlipidemia which also correlates with hypoalbuminemia. In other severely hyperlipidemic states (e.g. Familial Hypercholesterolemia), the level of oxidized low-density lipoprotein (oxLDL) is markedly elevated. Forms of oxidized LDL interact with monocytes and macrophages leading to expression of Tissue Factor (TF), a procoagulant molecule. Furthermore, monocytes and macrophages activated in this fashion also release microparticles, small cell-membrane derived vesicles, that also express TF and participate in initiating intravascular clot formation. the investigator hypothesizes that the hyperlipidemia of the nephrotic syndrome leads to elevations in oxidized LDL and in turn, elevations in microparticle Tissue Factor (MP-TF) and its activity. The investigator also hypothesizes that serum albumin levels will inversely correlate with hyperlipidemia as well as oxLDL levels and MP-TF activity. Here, the investigator will study the effect of treatment with HMGCoA reductase inhibitors (statins) on ox LDL and MP-TF activity patients with NS.
- Conditions
- Nephrotic Syndrome, Hyperlipidemia
- Being tested
- Pravastatin
- Keywords
- nephrotic, hyperlipidemia, oxLDL, kidney
- Medical subject headings
- Nephrotic Syndrome, Hyperlipidemias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PravastatinDrug
Also called Pravachol
After collecting baseline plasma samples, participants will receive pravastatin 20mg daily. After 6 weeks, we will collect samples and safety data. Subsequent statin therapy will be at the discretion of the treating physician.
| Study group | Role | What they receive |
|---|---|---|
| pravastatin | Other | All participants will receive pravastatin 20mg daily Receives: Drug: Pravastatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in Microparticle tissue factor (MP-TF) activity
The investigator will measure MP-TF activity . Microparticles will be isolated from platelet-free plasma (PFP) in a two-step sequential ultracentrifugation (20,000xg) process. Following the addition of Factor VIIa, Factor X and CaCl2, FXa generation is measured. Recombinant human relipidated TF will be used as a standard. TF-dependent plasma coagulation activity (PCA)generation is calculated by subtracting PCA generated in the presence of blocking antibodies from the amount of total PCA generated in the presence of an IgG control. The use of MP-TF activity as an outcome measure is unique in that it reflects both the pathophysiology and is a measure of PCA that correlates with VTE events
Measured: tested at baseline and week 6
Secondary outcomes (1)
Changes in plasma coagulation activation
the investigator will also perform other more routine measures of plasma coagulation activation to determine the overall effect of hyperlipidemia in NS that may include TF-independent mechanisms.
Thrombin-antithrombin complexes (TAT) also provide information regarding the downstream effect of Tissue Factor in the coagulation cascade.
- D-Dimer measurement - human D-Dimer ELISA
- Thrombin-antithrombin complexes (TAT) -
Other covariates:
Fasting lipid profile (including direct LDL measurement), serum albumin, proteinuria (by urine protein/creatinine ratio), estimated Glomerular Filtration Rate (eGFR), immunosuppressive therapy, age, sex, race.
Measured: baseline and week6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2013 (estimated)
- Study startMay 2012
- Primary completionJan 2017
- Study completionJan 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Nephrotic SyndromeStudies of the same condition, open and under way.
- More trials run by University of North Carolina, Chapel HillThe 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
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Vimal Derebail, MD, Principal investigator, University of North Carolina, Chapel Hill
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01845428
- Sponsor's protocol ID
- 12-0789
- Other IDs
- U54DK083912
- Acronym
- OxLDL
- Status last verified
- Aug 2018
- First submitted
- 24 Apr 2013
- Last updated
- 29 Aug 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessment of the Efficacy of Lipid-lowering Agents to Limit Lipid Oxidation and Activation of the Clotting System in Patients With the Nephrotic Syndrome: a Pilot Study.
- ClinicalTrials.gov ID
- NCT01845428
- Acronym / sponsor ID
- OxLDL / 12-0789
- Conditions
- Nephrotic Syndrome, Hyperlipidemia
- Keywords
- nephrotic, hyperlipidemia, oxLDL, kidney
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- May 2012 (actual)
- Primary completion
- Jan 2017 (actual)
- Study completion
- Jan 2017 (actual)
- First posted
- 3 May 2013 (estimated)
- 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.
The purpose of this research study is to learn if using statin in patients with nephrotic syndrome could lower the risk of blood clots. Nephrotic syndrome is a collection of signs and symptoms that occur when the glomeruli -the tiny filters that work in the kidney- leak protein in the urine.
One of the symptoms associated with nephrotic syndrome is hyperlipidemia: too much bad cholesterol (LDL). This bad cholesterol could be linked to the increased risk of blood clots in patients with nephrotic syndrome. The study doctors would like to see if taking a statin drug to reduce the amount of bad cholesterol could reduce the risk of blood clots.
Detailed description
Venous thromboembolic (VTE) events are common in the nephrotic syndrome (NS) occurring in up to 30% of patients when systematically screened. The investigator proposes to explore a novel mechanism for the increased clot formation in NS. To date, the only consistently identified underlying risk factor for VTEs is severe hypoalbuminemia related to the NS. The underlying pathophysiology related to VTE in NS remains poorly understood and has previously been ascribed to dysregulation of pro- and anticoagulant clotting factors due to urinary protein losses and reflected by the low serum albumin. However, the direct evidence for this mechanism is inconsistent and relatively poor. Another feature of NS is that of severe hyperlipidemia which also correlates with hypoalbuminemia. In other severely hyperlipidemic states (e.g. Familial Hypercholesterolemia), the level of oxidized low-density lipoprotein (oxLDL) is markedly elevated. Forms of oxidized LDL interact with monocytes and macrophages leading to expression of Tissue Factor (TF), a procoagulant molecule. Furthermore, monocytes and macrophages activated in this fashion also release microparticles, small cell-membrane derived vesicles, that also express TF and participate in initiating intravascular clot formation. the investigator hypothesizes that the hyperlipidemia of the nephrotic syndrome leads to elevations in oxidized LDL and in turn, elevations in microparticle Tissue Factor (MP-TF) and its activity. The investigator also hypothesizes that serum albumin levels will inversely correlate with hyperlipidemia as well as oxLDL levels and MP-TF activity. Here, the investigator will study the effect of treatment with HMGCoA reductase inhibitors (statins) on ox LDL and MP-TF activity patients with NS.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| pravastatin | Other | Drug: PravastatinAll participants will receive pravastatin 20mg daily |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| PravastatinAlso: PravacholAfter collecting baseline plasma samples, participants will receive pravastatin 20mg daily. After 6 weeks, we will collect samples and safety data. Subsequent statin therapy will be at the discretion of the treating physician. | Drug | pravastatin |
Primary outcome
Changes in Microparticle tissue factor (MP-TF) activity
Time frame: tested at baseline and week 6
The investigator will measure MP-TF activity . Microparticles will be isolated from platelet-free plasma (PFP) in a two-step sequential ultracentrifugation (20,000xg) process. Following the addition of Factor VIIa, Factor X and CaCl2, FXa generation is measured. Recombinant human relipidated TF will be used as a standard. TF-dependent plasma coagulation activity (PCA)generation is calculated by subtracting PCA generated in the presence of blocking antibodies from the amount of total PCA generated in the presence of an IgG control. The use of MP-TF activity as an outcome measure is unique in that it reflects both the pathophysiology and is a measure of PCA that correlates with VTE events
1 secondary outcome
Changes in plasma coagulation activation
Time frame: baseline and week6
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 29 Aug 2018.
- general web site of UNC Kidney CenterLink provided by the sponsor.
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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.
Vimal Derebail, MD principal investigator
University of North Carolina, Chapel Hill
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Pravastatin in people with Nephrotic Syndrome and Hyperlipidemia, run by University of North Carolina, Chapel Hill at 1 site 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?
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 29 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Changes in Microparticle tissue factor (MP-TF) activity (time frame: tested at baseline and week 6). 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 29 Aug 2018.