Development of a Novel Glutamate Receptor Ligand for PET Scans in Neuropsychiatric Systemic Lupus Erythematosus

NCT02456168 | Completed

• 1 other identifier: PET CNS5161
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Cognitive impairment occurs in as many as 80% of lupus patients and affective disorders, depression and anxiety, are also common. Both of these problems contribute significantly to disease burden and disability. Associations between serum anti-NMDAR Aab and cognitive and behavioral changes in human SLE have remained controversial, however, elevated titers of these Aabs in cerebrospinal fluid (CSF) correlate with severe central nervous system manifestations, such as coma and psychosis. The aim is to study the progression of disease (cognitive and behavioral impairment) over a 2 year period in SLE subjects with neuropsychologic and behavioral testing and correlates of disease progression using resting FDG-PET and serum Anti-NMDAR Aab. The correlations between hippocampal hypermetabolism, Anti-NMDAR Aab and memory impairment observed in the cross-sectional studies will be validated by baseline measurements in the proposed studies.

Conditions

Systemic Lupus Erythematosus

Keywords

Lupus; SLE

Outcome Measures

Primary Outcomes (1)

• Changes in brain activity

  hippocampal metabolism from baseline over the 2 years

Secondary Outcomes (1)

• Use of PET ligand CNS 5161 tracer as an assessment and imaging biomarker for regional brain dysfunction

  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

Study Arms (2)

SLE

Healthy control

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Probability Sample

Study Population

24 lupus subjects will be recruited based on the following Inclusion/Exclusion criteria and serum anti-NMDAR antibody status. The investigators are not selecting for SLE patients known to have cognitive or psychiatric disturbances because attribution of these problems is very difficult given the confounding effects of medications, co-morbid disease, metabolic disturbances and infections. The investigators are interested in the effects of the anti-NMDAR Aab and will stratify lupus subject population on this variable. The PET and MRI imaging studies will be performed only during times of stable disease activity and medication use to avoid confounding influences of acute changes in disease activity and steroids/immunosuppressive medications. The 17 healthy control subjects should have no history of chronic illness and be on no prescribed medications other than oral contraception. Subjects older than age 55 will also be excluded to avoid confounding effects of age on cognitive testing.

You may qualify if:

• Must be ≥18 and ≤55 years of age.
• Must fulfill the current American College of Rheumatology (ACR) revised criteria for the diagnosis of SLE.
• Must be willing and able to sign informed consent.
• Must have stable disease activity and medication doses for 8 weeks prior to screening.

You may not qualify if:

• History of neurological diseases including head injury resulting in a loss of consciousness, strokes (secondary to hypertension, atherosclerosis, diabetes), seizures, toxic exposure, any difficulties at birth, mental retardation.
• History of documented transient ischemic attacks within six months of screening.
• Currently taking anti-convulsant medication.
• Limited fluency with English that in the opinion of the investigator would limit the subject's performance on the ACR battery of cognitive tests or the N-back task chosen for the working memory task during the PET scan.
• History of illicit drug use (cocaine, cannabis, heroin) that can result in altered cognition.
• Increased disease activity within 8 weeks defined by an increase in SLEDAI by 3 points or more, exclusive of points from serologies.
• Any increase in steroid dose or addition of disease modifying agents within 8 weeks.
• Exceeding the weight limit on the MRI scanner.
• Suffering from claustrophobia.
• Have any of the following: cardiac pacemakers, auto defibrillators, neural stimulators, aneurysm clips, metallic prostheses, cochlear implants, any implanted devices (pumps, infusion devices, stents), permanent eye make-up, IUD's, shrapnel injuries.
• Current use of anxiolytic, antidepressant or antipsychotic medications.
• Pregnant and/or lactating women
• A glomerular filtration rate less than ≤60 mL/min or any evidence of active renal disease from any cause that would put the subject at risk for increased toxicity from gadolinium contrast for the MRI study.
• The presence of uncontrolled or severe hypertension, diabetes mellitus or liver disease that would increase the risk of increased toxicity from gadolinium contrast.

Sponsors & Collaborators

• Northwell Health: lead

Study Sites (1)

The Feinstein Institute for Medical Research

Manhasset, New York, 11030, United States

Location

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Meggan Mackay, MD

  Northwell Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Investigator, MD

Study Record Dates

• First Submitted: May 15, 2015
• First Posted: May 28, 2015
• Study Start: January 21, 2014
• Primary Completion: October 28, 2020
• Study Completion: October 28, 2020
• Last Updated: February 15, 2023

Record last verified: 2023-02

Locations

US (1)