SLE is a chronic autoimmune disease that often involves multiple systems and organs of the body. An autoimmune disease is one which your immune system attacks the cells and tissues in different parts of the body. SLE is characterized by inflammation that leads to tissue damage in many different organ systems. Lupus can cause fever, joint pains, rashes, and other symptoms. It can also affect organs such as the skin, the muscles, the kidneys, the heart, the lungs, the blood and the brain. The exact cause of SLE is not known. Problems with memory and concentration are common in lupus; these problems are called cognitive problems. Cognitive problems can be caused by things like depression, fatigue, medication and infections. However, previous studies that have been done in animal models of lupus and in lupus patients suggest that inflammation due to lupus can affect the brain directly. This research study is being done to test the effects of centrally-acting ACE inhibitor, named lisinopril, on resting metabolism in the brain and on cognitive function. The investigators will see if Lisinopril will decrease resting metabolism in the brain and improve cognitive function (memory and concentration) compared to a non-centrally acting ACE inhibitor called benazepril.
The study is a randomized, double blind, controlled, multi-center clinical trial to test the efficacy of a CA-ACEi, lisinopril, compared to a nonCA-ACEi, benazepril, for CI in SLE as measured by improvement in regional resting brain hypermetabolism and cognitive testing. The study will also investigate the impact of CA-ACEi compared to nonCA-ACEi on microglia cell activation as measured by PBR28 binding, behavioral function, circulating inflammatory cytokines and whole blood gene expression. The target population is SLE subjects between the ages of 18 and 55 that have stable disease activity and have no history of active or prior CNS disease of any kind. If applicable, subjects must be on stable doses of corticosteroids (less than or equal to 10 mg daily of prednisone) and non-increasing doses of other immunosuppressive medications for at least 4 weeks prior to screening.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
36
Tablets will be taken by oral administration daily, based on titration
Tablets will be taken by oral administration daily, based on titration
Yale University School of Medicine
New Haven, Connecticut, United States
Northwell Rheumatology
Great Neck, New York, United States
Andrew Shaw
Manhasset, New York, United States
New York University School of Medicine
New York, New York, United States
Columbia University Medical Center
New York, New York, United States
Hospital for Special Surgery
New York, New York, United States
Albert Einstein College of Medicine
The Bronx, New York, United States
Brain Metabolism
The primary outcome measure for evaluation of the primary objective will be the change in regional metabolism between baseline and 12 months in the posterior putamen/GP/thalamus on FDG-PET imaging.
Time frame: 3 years
PBR28
PBR28 Imaging: Normality of the imaging data will be tested with the Shapiro-Wilkes Test. If normally distributed, the two-sample Student's t-test and the MMRMA will be used to compare the \[11C\]-PBR28 Standardized Uptake Value Ratios (SUVR; primary imaging endpoint for microglial cell activation) in the regions of interest between the CA-ACEi and nonCA-ACEi treated groups at baseline and over time, respectively. The regions of interest include the posterior putamen/GP/thalamus, hippocampus, temporal lobes, orbitofrontal cortex, sensorimotor cortex and occipital lobes. If the data are found to be non-normally distributed, corresponding non-parametric tests will be used for statistical analyses.
Time frame: 3 years
Automated Neuropsychological Assessment Metrics (ANAM)
Changes in cognitive testing from baseline to 6 and 12 months as measured by Automated Neuropsychological Assessment Metrics (ANAM) subtest
Time frame: 3 years
2x2 spatial memory task
Changes in cognitive testing from baseline to 6 and 12 months as measured by 2x2 spatial memory task
Time frame: 3 years
Spatial Navigation Task
Changes in cognitive testing from baseline to 6 and 12 months as measured by Spatial Navigation Task
Time frame: 3 years
Mood Assessments
Changes in mood from baseline to 6 and 12 months as measured by the Beck Depression Inventory and the ANAM Mood Assessments
Time frame: 3 years
Patient Reported Outcomes
Changes in patient reported outcomes; the PROMIS-Cognitive Function, LFA-REAL Patient Report, LupusPRO and the patient global assessment, between baseline, 6 and 12 months
Time frame: 3 years
Disease Activity
Changes in disease activity between baseline and 12 months as measured by the SLEDAI-2K, the SELENA SLEDAI Flare Index, LFA-REAL Clinician Report and physician global assessment
Time frame: 3 years
Microglial Cell Activation
Changes in microglial cell activation from baseline to 12 months as measured by changes in regional volume of distribution of PBR28 tracer binding
Time frame: 3 years
Inflammatory Cytokines
Changes in levels of circulating inflammatory cytokines between baseline and 6 and 12 months measured by proteomics on serum using Meso Scale Discovery platform
Time frame: 3 years
RNA-Seq
Changes in RNA-Seq transcriptome profiles of whole blood between baseline and 6 and 12 months collected in PAXgene blood RNA tubes.
Time frame: 3 years
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