Systemic Lupus ErythematosusNCT02456168
Development of a Novel Glutamate Receptor Ligand for PET Scans in Neuropsychiatric Systemic Lupus Erythematosus
An observational study of Systemic Lupus Erythematosus, run by Northwell Health at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Systemic Lupus Erythematosus
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Jan 2014to 28 Oct 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
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.
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 14Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
The Feinstein Institute for Medical Research
Manhasset, New York, 11030
About this study
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.
Read the detailed description
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).
- Conditions
- Systemic Lupus Erythematosus
- Keywords
- Lupus, SLE
- Medical subject headings
- Lupus Erythematosus, Systemic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| SLE | Not described | |
| Healthy control | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in brain activity
Measured: 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
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 May 2015 (estimated)
- Study start21 Jan 2014
- Primary completion28 Oct 2020
- Study completion28 Oct 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Systemic Lupus ErythematosusStudies of the same condition, open and under way.
- More trials run by Northwell HealthThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwell Health
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Meggan Mackay, MD, Northwell Health
- Investigators
- Meggan Mackay, MD, Principal investigator, Northwell Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02456168
- Sponsor's protocol ID
- PET CNS5161
- Status last verified
- Feb 2023
- First submitted
- 15 May 2015
- Last updated
- 15 Feb 2023
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Development of a Novel Glutamate Receptor Ligand for PET Scans in Neuropsychiatric Systemic Lupus Erythematosus
- ClinicalTrials.gov ID
- NCT02456168
- Acronym / sponsor ID
- PET CNS5161
- Conditions
- Systemic Lupus Erythematosus
- Keywords
- Lupus, SLE
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Northwell HealthUniversity, hospital or other
- Study start
- 21 Jan 2014 (actual)
- Primary completion
- 28 Oct 2020 (actual)
- Study completion
- 28 Oct 2020 (actual)
- First posted
- 28 May 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| SLE | – | – |
| Healthy control | – | – |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- 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.
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Changes in brain activity
Time frame: hippocampal metabolism from baseline over the 2 years
1 secondary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2023.
Related trials for Systemic Lupus Erythematosus
Not yet recruitingPhase 1
An Ascending Dose Study of DKB903 in Participants With Rheumatoid Arthritis (RA) and Participants With Systemic Lupus Erythematosus (SLE)
Rheumatoid Arthritis and Systemic Lupus Erythematosus
RecruitingPhase 4
Dapagliflozin in Active Lupus Nephritis
Lupus Nephritis (LN)
RecruitingObservational study
Electroencephalogram Recording in Patients With Systemic Lupus Erythematosus
Systemic Lupus Erythematosus
RecruitingObservational study
Deciphering the Genetic Architecture of Autoimmune Diseases
Autoimmune Diseases
RecruitingPhase 1
A Trial in Healthy Adult Participants and Adults With Autoimmune Diseases to Test How HBM7020 is Tolerated and How it Behaves in the Body
Rheumatoid Arthritis, Systemic Lupus Erythematosus
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Meggan Mackay, MD principal investigator
Northwell Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Systemic Lupus Erythematosus, run by Northwell Health at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in brain activity (time frame: hippocampal metabolism from baseline over the 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Feb 2023.