Development of a Novel Glutamate Receptor Ligand for PET Scans in Neuropsychiatric Systemic Lupus Erythematosus
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|ClinicalTrials.gov Identifier: NCT02456168|
Recruitment Status : Active, not recruiting
First Posted : May 28, 2015
Last Update Posted : March 13, 2019
|Condition or disease|
|Systemic Lupus Erythematosus|
Neuropsychiatric lupus is comprised of numerous, complex central and peripheral nervous system symptoms whose pathophysiologic mechanisms remain poorly understood. Cross-reactive anti-dsDNA antibodies have been shown to bind NR2A/NR2B subunits of the N-methyl D-aspartate receptor (NMDAR) on neurons and synergize with glutamate in a concentration dependent manner to either modulate receptor function or cause an excitotoxic, non-inflammatory neuronal death. Mice immunized to express anti-NMDAR Aab demonstrate a causal relationship between anti-NMDAR Aab and persistent behavioral and cognitive neuropathology following compromise to the blood brain barrier (BBB) which is necessary for Aab access to the brain.
The investigators' previous cross-sectional FDG-PET studies of resting brain glucose metabolism demonstrate robust hypermetabolism in the hippocampus of SLE subjects that associates independently with serum Anti-NMDAR Aab titer and impaired memory. Moreover, the combination of hippocampus hypermetabolism and elevated serum titers of Anti-NMDAR Aab has a higher predictive value for memory impairment than either variable alone. These significant correlations must be tested in a longitudinal study to evaluate the utility of FDG-PET as a biomarker for Anti-NMDAR Aab-mediated brain damage. The proposed longitudinal studies will inform the investigators about correlates of cognitive and behavioral change over time using FDG-PET imaging (Aim 1). Additionally, the investigators will explore NMDAR biology with a novel PET ligand, [11C]-CNS5161, used to localize and quantify NMDAR activation (Aim 2) and explore the role of blood brain barrier (BBB) integrity in cognitive and behavioral impairment (Aim 3).
|Study Type :||Observational|
|Actual Enrollment :||30 participants|
|Official Title:||Development of a Novel Glutamate Receptor Ligand for PET Scans in Neuropsychiatric Systemic Lupus Erythematosus|
|Study Start Date :||January 2015|
|Estimated Primary Completion Date :||December 2021|
|Estimated Study Completion Date :||December 2021|
- Changes in brain activity [ Time Frame: hippocampal metabolism from baseline over the 2 years ]
- Use of PET ligand CNS 5161 tracer as an assessment and imaging biomarker for regional brain dysfunction [ Time Frame: Specific activity of CNS5161, determined by the UV absorbance of the radioactive peak as compared with a standard curve of CNS5161 from baseline over the 2 years ]
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Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02456168
|United States, New York|
|The Feinstein Institute for Medical Research|
|Manhasset, New York, United States, 11030|
|Principal Investigator:||Meggan Mackay, MD||The Feinstein Institute for Medical Research|