Systemic Lupus ErythematosusPhase 2NCT04486118
Centrally Acting ACE Inhibition in SLE
A Phase 2 study testing Lisinopril Pills and Benazepril Pill in people with Systemic Lupus Erythematosus, run by Northwell Health at 7 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Systemic Lupus Erythematosus
- What is being tested?
- Lisinopril Pills and Benazepril Pill
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 7 sitesUnited States
- Study dates
- 1 Oct 2021to 1 Mar 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
- No healthy volunteers
- Adult
Who may be able to join
- Subject must be able to understand and provide informed consent
- Subjects must be ≥18 and ≤65 years of age: subjects with age > 65 will be excluded to avoid confounding effects of age on cognitive testing.
- Subjects must fulfill the 1997 American College of Rheumatology (ACR) revised criteria for the diagnosis of SLE or the Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) Criteria or the EULAR/ ACR 2019 criteria for SLE.
- Subjects must have stable disease activity and medication doses for 4 weeks prior to screening. Stable disease activity is defined as no increase in disease activity requiring an increase or addition of immunosuppressive medications.
- If on corticosteroids, subjects must be on a dose that is ≤ prednisone 10 mg daily, or the equivalent.
- Must have increased resting metabolism in the posterior putamen/GP/thalamus on the screening FDG-PET scan that is
- > 1.647 for non-Black SLE subjects and
- > 1.699 for Black SLE subjects.
Who cannot join
- Inability or unwillingness of a participant to give written informed consent or comply with study protocol.
- History of neurological diseases including, but not limited to, severe head injury or history of brain surgery, stroke, seizure, toxic exposure, mental retardation, multiple sclerosis, dementia, encephalitis.
- History of documented transient ischemic attacks within 6 months of screening.
- Addition of belimumab or rituximab within 3 months of screening and/or addition of disease modifying drugs (such as mycophenolate, methotrexate, azathioprine, leflunomide, voclosporin, tacrolimus) within 3 months of screening.
- History of illicit drug or alcohol dependence/abuse within the past 12 months.
- Current use of anxiolytic, anticonvulsant, antidepressant or antipsychotic medications other than specific serotonin reuptake inhibitors (SSRIs) and gabapentin. SSRIs are allowed if the subject is on a stable dose for 12 weeks prior to the screening FDG-PET scan and is expected to remain on the same SSRI throughout the trial. Gabapentin is allowed if used on a PRN basis for pain or reason other than seizure disorder and the subject is willing not to take it for a minimum of 2 weeks prior to brain imaging or neuropsychological assessments.
Show all 25Show fewer
- Current and/or chronic use of narcotic analgesia for > 3 weeks within the last 3 months.
- Increased disease activity within 4 weeks of screening defined by an increase in SLEDAI by 3 points or more, exclusive of points from serologies, which prompts an increase in or new addition of SLE medications.
- History of a diagnosis of a primary psychiatric disorder requiring medication that preceded the diagnosis of SLE.
- Current active acute infections requiring antibiotics within 2 weeks of screening and chronic known infections (eg. hepatitis B, C, and/or HIV).
- Co-existing other autoimmune disease(s) other than autoimmune thyroid disease or secondary Sjogren's Syndrome.
- Pregnant and/or lactating women and/or women unwilling to use an acceptable form of contraception.
- The presence of uncontrolled, severe hypertension, diabetes or heart disease.
- History of hereditary or idiopathic angioedema.
- Impaired renal function with an eGFR< 60%.
- Current use of aliskiren in diabetic patients.
- Current use of naltrexone or chronic minocycline use; both are agents also known to alter microglia activation.
- Use of a centrally acting ACE inhibitor (Lisinopril, fosinopril, ramipril, captopril, perindopril, prinivil, monopril, trandolapril) or angiotensin receptor blocker for more than 4 weeks within the past 1 year. Non-centrally acting ACE inhibitors are allowed if the subject is willing to be randomized to Lisinopril or benazepril instead of their non-centrally acting ACE inhibitor.
- Known intolerance to ACE inhibitors.
- Presence of any active medical condition that in the opinion of the investigator may contribute to cognitive and/or behavioral disturbances.
- Use of investigational drugs within 30 days or 5 half-lives before Visit 1 (Day 1), whichever is longer.
- Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study.
- 23. A systolic blood pressure less than 100 mmHg at screening. If the investigator feels that the patient is insufficiently hydrated, the patient may be re-evaluated for blood pressure within the screening period.
- 24. Current treatment with Cyclophosphamide. 25. The presence of suicidal ideation on the Beck Depression Inventory at screening or sufficient depressive symptoms to warrant intervention with pharmacologic therapy and/or referral for treatment.
- 26. For subjects consenting to the MRI scans: the presence of ferromagnetic implants or devices that cannot be removed and/or a history of claustrophobia or intolerance of MRI.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Northwell Rheumatology
Great Neck, New York, 11021
Andrew Shaw
Manhasset, New York, 11030
Yale University School of Medicine
New Haven, Connecticut, 06519
New York University School of Medicine
New York, New York, 10016
Columbia University Medical Center
New York, New York, 10032
Hospital for Special Surgery
New York, New York, 20021
Albert Einstein College of Medicine
The Bronx, New York, 10461
About this study
Official title: A Novel Phase 2 Double-blind, Randomized, Controlled Clinical Trial to Evaluate the Efficacy of Centrally Acting, Non-toxic ACE Inhibition in Cognitive Impairment Associated With SLE
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.
Read the detailed description
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.
- Conditions
- Systemic Lupus Erythematosus
- Being tested
- Lisinopril Pills, Benazepril Pill
- 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.
Lisinopril PillsDrug
Tablets will be taken by oral administration daily, based on titration
Benazepril PillDrug
Tablets will be taken by oral administration daily, based on titration
| Study group | Role | What they receive |
|---|---|---|
| CA-ACEi | Active comparator | Enrolled subjects will begin treatment with a low dose of study drug (5 mg) Study drug will then be titrated up as follows, provided the increased dose is tolerated:
Day 3-15 (dosing begins after completion of FIMR Visit 1.1): 5 mg Day 29: 10 mg Day 43: 20 mg Day 57: 40 mg if tolerated Subjects will be required to achieve and maintain a minimum dose of 20 mg daily to ensure adequate dosage of the ACE inhibitor. Receives: Drug: Lisinopril Pills |
| nonCA-ACEi | Placebo comparator | Enrolled subjects will begin treatment with a low dose of study drug (5 mg) Study drug will then be titrated up as follows, provided the increased dose is tolerated:
Day 3-15 (dosing begins after completion of FIMR Visit 1.1): 5 mg Day 29: 10 mg Day 43: 20 mg Day 57: 40 mg if tolerated Subjects will be required to achieve and maintain a minimum dose of 20 mg daily to ensure adequate dosage of the ACE inhibitor. Receives: Drug: Benazepril Pill |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 3 years
Secondary outcomes (10)
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.
Measured: 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
Measured: 3 years
2x2 spatial memory task
Changes in cognitive testing from baseline to 6 and 12 months as measured by 2x2 spatial memory task
Measured: 3 years
Spatial Navigation Task
Changes in cognitive testing from baseline to 6 and 12 months as measured by Spatial Navigation Task
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2020
- Study start1 Oct 2021
- Primary completion3 Jun 2025
- Study completion1 Mar 2026 (estimated)
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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Northwell Health
- Sponsor type
- University, hospital or other
- Collaborators
- Lupus Research Alliance
- Responsible party
- Principal investigator, Meggan Mackay, MD, Northwell Health
- Investigators
- Meggan Mackay, MD, Principal investigator, Northwell Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04486118
- Sponsor's protocol ID
- 20-0034
- Status last verified
- Sep 2025
- First submitted
- 28 Oct 2019
- Last updated
- 19 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Novel Phase 2 Double-blind, Randomized, Controlled Clinical Trial to Evaluate the Efficacy of Centrally Acting, Non-toxic ACE Inhibition in Cognitive Impairment Associated With SLE
- ClinicalTrials.gov ID
- NCT04486118
- Acronym / sponsor ID
- 20-0034
- Conditions
- Systemic Lupus Erythematosus
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- Northwell HealthUniversity, hospital or other
- Collaborators
- Lupus Research Alliance
- Study start
- 1 Oct 2021 (actual)
- Primary completion
- 3 Jun 2025 (actual)
- Study completion
- 1 Mar 2026 (estimated)
- First posted
- 24 Jul 2020 (actual)
- 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.
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.
Detailed description
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CA-ACEi | Active comparator | Drug: Lisinopril PillsEnrolled subjects will begin treatment with a low dose of study drug (5 mg) Study drug will then be titrated up as follows, provided the increased dose is tolerated: Day 3-15 (dosing begins after completion of FIMR Visit 1.1): 5 mg Day 29: 10 mg Day 43: 20 mg Day 57: 40 mg if tolerated Subjects will be required to achieve and maintain a minimum dose of 20 mg daily to ensure adequate dosage of the ACE inhibitor. |
| nonCA-ACEi | Placebo comparator | Drug: Benazepril PillEnrolled subjects will begin treatment with a low dose of study drug (5 mg) Study drug will then be titrated up as follows, provided the increased dose is tolerated: Day 3-15 (dosing begins after completion of FIMR Visit 1.1): 5 mg Day 29: 10 mg Day 43: 20 mg Day 57: 40 mg if tolerated Subjects will be required to achieve and maintain a minimum dose of 20 mg daily to ensure adequate dosage of the ACE inhibitor. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Subject must be able to understand and provide informed consent
- Subjects must be ≥18 and ≤65 years of age: subjects with age > 65 will be excluded to avoid confounding effects of age on cognitive testing.
- Subjects must fulfill the 1997 American College of Rheumatology (ACR) revised criteria for the diagnosis of SLE or the Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) Criteria or the EULAR/ ACR 2019 criteria for SLE.
- Subjects must have stable disease activity and medication doses for 4 weeks prior to screening. Stable disease activity is defined as no increase in disease activity requiring an increase or addition of immunosuppressive medications.
- If on corticosteroids, subjects must be on a dose that is ≤ prednisone 10 mg daily, or the equivalent.
Key exclusion criteria (25 listed)
- Inability or unwillingness of a participant to give written informed consent or comply with study protocol.
- History of neurological diseases including, but not limited to, severe head injury or history of brain surgery, stroke, seizure, toxic exposure, mental retardation, multiple sclerosis, dementia, encephalitis.
- History of documented transient ischemic attacks within 6 months of screening.
- Addition of belimumab or rituximab within 3 months of screening and/or addition of disease modifying drugs (such as mycophenolate, methotrexate, azathioprine, leflunomide, voclosporin, tacrolimus) within 3 months of screening.
- History of illicit drug or alcohol dependence/abuse within the past 12 months.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lisinopril PillsTablets will be taken by oral administration daily, based on titration | Drug | CA-ACEi |
| Benazepril PillTablets will be taken by oral administration daily, based on titration | Drug | nonCA-ACEi |
Primary outcome
Brain Metabolism
Time frame: 3 years
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.
10 secondary outcomes
PBR28
Time frame: 3 years
Automated Neuropsychological Assessment Metrics (ANAM)
Time frame: 3 years
2x2 spatial memory task
Time frame: 3 years
Spatial Navigation Task
Time frame: 3 years
Mood Assessments
Time frame: 3 years
Patient Reported Outcomes
Time frame: 3 years
Disease Activity
Time frame: 3 years
Microglial Cell Activation
Time frame: 3 years
Inflammatory Cytokines
Time frame: 3 years
RNA-Seq
Time frame: 3 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2025.
- Individual participant dataSharing planned: No
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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
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lisinopril Pills and Benazepril Pill in people with Systemic Lupus Erythematosus, run by Northwell Health at 7 sites 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 8 inclusion and 25 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: under way, not looking for participants, as of the sponsor's last update on 19 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
Brain Metabolism (time frame: 3 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 19 Sep 2025.