Lipid Lowering Agents to Limit Lipid Oxidation and Activation of Clotting System in Nephrotic Syndrome (OxLDL)

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by University of North Carolina, Chapel Hill
Sponsor:
Information provided by (Responsible Party):
Vimal Derebail, MD, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:
NCT01845428
First received: April 24, 2013
Last updated: December 27, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Nephrotic Syndrome
Hyperlipidemia
Drug: Pravastatin
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
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.

Resource links provided by NLM:


Further study details as provided by University of North Carolina, Chapel Hill:

Primary Outcome Measures:
  • Changes in Microparticle tissue factor (MP-TF) activity [ Time Frame: tested at baseline, week 3 and week 6 ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • Changes in plasma coagulation activation [ Time Frame: baseline, week 3 and week6 ] [ Designated as safety issue: No ]

    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.

    1. D-Dimer measurement - human D-Dimer ELISA
    2. 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.



Estimated Enrollment: 10
Study Start Date: May 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
pravastatin
All participants will receive pravastatin 10mg daily
Drug: Pravastatin
After collecting baseline plasma samples, participants will receive pravastatin 10mg daily. After 3 weeks, we will collect plasma and safety data and if tolerated well, will increase the dose to 20mg daily. After an additional 3 weeks of therapy, we will repeat sample and data collection. Subsequent statin therapy will be at the discretion of the treating physician.
Other Name: parachol

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

-

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01845428

Locations
United States, North Carolina
Unc Kidney Center Recruiting
Chapel Hill, North Carolina, United States, 27599-7155
Contact: Vimal K Derebail, MD    919-966-2561 ext 225    vimal_derebail@med.unc.edu   
Contact: Anne Froment    919-966-2561 ext 247    anne_froment@med.unc.edu   
Principal Investigator: Vimal K Derebail, MD         
Sponsors and Collaborators
University of North Carolina, Chapel Hill
Investigators
Principal Investigator: Vimal Derebail, MD University of North Carolina, Chapel Hill
  More Information

Additional Information:
No publications provided

Responsible Party: Vimal Derebail, MD, Assistant professor, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT01845428     History of Changes
Other Study ID Numbers: 12-0789, U54-DK-083912
Study First Received: April 24, 2013
Last Updated: December 27, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of North Carolina, Chapel Hill:
nephrotic
hyperlipidemia
oxLDL
kidney

Additional relevant MeSH terms:
Hyperlipidemias
Nephrotic Syndrome
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Nephrosis
Kidney Diseases
Urologic Diseases
Hypolipidemic Agents
Pravastatin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Anticholesteremic Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 24, 2014