Centrally Acting ACE Inhibition in SLE

NCT04486118 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 20-0034
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 7

Brief 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. 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.

Conditions

Systemic Lupus Erythematosus

Outcome Measures

Primary Outcomes (1)

• 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.

  3 years

Secondary Outcomes (10)

• PBR28

  3 years

• Automated Neuropsychological Assessment Metrics (ANAM)

  3 years

• 2x2 spatial memory task

  3 years

• Spatial Navigation Task

  3 years

• Mood Assessments

  3 years

Study Arms (2)

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.

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.

Drug: Benazepril Pill

Interventions

Lisinopril Pills DRUG

Tablets will be taken by oral administration daily, based on titration

CA-ACEi

Benazepril Pill DRUG

Tablets will be taken by oral administration daily, based on titration

nonCA-ACEi

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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%.

Sponsors & Collaborators

• Northwell Health: lead
• Lupus Research Alliance: collaborator

Study Sites (7)

Yale University School of Medicine

New Haven, Connecticut, 06519, United States

Location

Northwell Rheumatology

Great Neck, New York, 11021, United States

Location

Andrew Shaw

Manhasset, New York, 11030, United States

Location

New York University School of Medicine

New York, New York, 10016, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Hospital for Special Surgery

New York, New York, 20021, United States

Location

Albert Einstein College of Medicine

The Bronx, New York, 10461, United States

Location

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Interventions

benazepril

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: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 28, 2019
• First Posted: July 24, 2020
• Study Start: October 1, 2021
• Primary Completion: June 3, 2025
• Study Completion: March 1, 2026
• Last Updated: September 19, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)