Clinical trial NCT03004001: Effect of PCSK9-Antibody (Alirocumab) on Dyslipidemia Secondary to Nephrotic Syndrome
Official title: Effect of PCSK9-Antibody (Alirocumab) on Dyslipidemia Secondary to Nephrotic Syndrome
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Nephrotic Syndrome
Keywords: Severe proteinuria
Dyslipidemia
Lead sponsor: Dallas VA Medical Center
Sponsor class: FED
Collaborators: name: Regeneron Pharmaceuticals
name: Aventis Pharmaceuticals
First posted: 2016-12-28
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The study purpose is to determine the hypolipidemic effect of Alirocumab co-administered with atorvastatin on levels of triglyceride-rich lipoproteins and LDL compared to monotherapy with atorvastatin in patients with dyslipidemia secondary to nephrotic syndrome.

Detailed description: The trial is randomized (1:1 alirocumab to placebo), double-blinded, placebo-controlled with a cross-over design. The trial will last 10 months and includes a 10 week washout period between study phases.Twenty adult subjects with dyslipidemia secondary to nephrotic syndrome and treated with atorvastatin will be recruited. Alirocumab or placebo will be co-administered biweekly. Safety, efficacy chemistries, vital signs, anthropometry and monitoring for adverse events also will done at each visit.

Eligibility criteria: Inclusion Criteria:

* Nephrotic Syndrome (NS) (FSGS, IMN or NS and type 2 DM)
* atorvastatin
* LDL C \>= 70 mg/dl or non-HDL C \>= 100 mg/dl
* Plasma trigycerides \< 800 mg/dl.
* Highly effective methods of contraception for pre-menopausal women
* Post-menopausal women must be amenorrheic for at least 12 months.

Exclusion Criteria:

* homozygous FH
* Fibrates within 6 weeks of screening visit
* Uncontrolled hypothyroidism
* Known history of hemorrhagic stroke
* Known history of loss of function of PCSK9
* use of systemic corticosteroids unless used as replacement therapy for pituitary/adrenal disease with a stable regimen for at least 6 weeks of randomization
* Previous treatment with at least a single dose of alirocumab or any other anti-PCSK9 monoclonal antibody
* Other conditions or situations per protocol
* Laboratory findings or contraindications to background therapies
* Warnings/precautions of use (when appropriate) as displayed in the respective national product labeling
* Any currently known contra-indication to study drug, pregnancy or breastfeeding of infants.

Primary outcomes:
measure: Levels of plasma lipoproteins
timeFrame: up to 10 months
Secondary outcomes:
measure: Levels of PCSK9
timeFrame: up to 10 months
measure: Triglyceride-rich lipoproteins (Remnants)
timeFrame: up to 10 months
measure: Lipidomics
timeFrame: up to 10 months
Other outcomes:
Locations:
city: Dallas
country: United States
facility: DallasVAMC
state: Texas
Study officials:
affiliation: Dallas VAMC
name: Gloria L Vega, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dallas VA Medical Center
name: Yin Oo, MD
role: STUDY_DIRECTOR
affiliation: Dallas VA Medical Center
name: Michael Concepcion, MD
role: STUDY_DIRECTOR
References:
citation: Vega GL, Grundy SM. Lovastatin therapy in nephrotic hyperlipidemia: effects on lipoprotein metabolism. Kidney Int. 1988 Jun;33(6):1160-8. doi: 10.1038/ki.1988.125.
citation: Toto RD, Grundy SM, Vega GL. Pravastatin treatment of very low density, intermediate density and low density lipoproteins in hypercholesterolemia and combined hyperlipidemia secondary to the nephrotic syndrome. Am J Nephrol. 2000 Jan-Feb;20(1):12-7. doi: 10.1159/000013549.
citation: Vega GL, Toto RD, Grundy SM. Metabolism of low density lipoproteins in nephrotic dyslipidemia: comparison of hypercholesterolemia alone and combined hyperlipidemia. Kidney Int. 1995 Feb;47(2):579-86. doi: 10.1038/ki.1995.73.
citation: Jin K, Park BS, Kim YW, Vaziri ND. Plasma PCSK9 in nephrotic syndrome and in peritoneal dialysis: a cross-sectional study. Am J Kidney Dis. 2014 Apr;63(4):584-9. doi: 10.1053/j.ajkd.2013.10.042. Epub 2013 Dec 4.