Centrally Acting ACE Inhibition in SLE

• Status: Not yet recruiting
• Trial end date: 2024-07-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Northwell Health
• Collaborator: Lupus Research Alliance
• Treatments: Benazepril; Lisinopril

Criteria

Inclusion Criteria:

1. Must be able to understand and provide informed consent. 2. Must be ≥18 and ≤55 years of age: subjects with age > 55 will be excluded to avoid confounding effects of age on cognitive testing.

3. 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 for SLE.

4. 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 change in medications.

5. Must be on a corticosteroid dose that is ≤ prednisone 10 mg daily, or equivalent.

6. 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.

1. Inability or unwillingness to give written informed consent or comply with study protocol

2. 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

3. History of documented transient ischemic attacks within 6 months of screening.

4. Limited fluency with English that in the opinion of the investigator would limit the subject's performance on the written assessments.

5. History of illicit drug or alcohol dependence/abuse within the past 12 months.

6. Current use of anxiolytic, anticonvulsant, antidepressant or antipsychotic medications.

7. Current and/or chronic use of narcotic analgesia for > 3 weeks within the last 3 months.

8. 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.

9. History of a diagnosis of a primary psychiatric disorder preceding SLE diagnosis.

10. Current active acute infections requiring antibiotics within 2 weeks of screening and chronic known infections (eg. hepatitis B, C, and/or HIV).

11. Co-existing other autoimmune disease(s) other than autoimmune thyroid disease and secondary Sjogren's Syndrome.

12. Pregnant and/or lactating women and/or women unwilling to use an acceptable form of contraception.

13. The presence of uncontrolled, severe hypertension, diabetes or heart disease.

14. History of hereditary or idiopathic angioedema.

15. Impaired renal function with an eGFR< 60%.

16. Current use of aliskiren in diabetic patients.

17. Current use of naltrexone or chronic minocycline use; both are agents also known to alter microglia activation.

18. Current use of an ACE inhibitor or angiotensin receptor blocker or use for more than 4 weeks within the past 1 year.

19. Known intolerance to ACE inhibitors.

20. Presence of any active medical condition that in the opinion of the investigator may contribute to cognitive and/or behavioral disturbances.

21. Use of investigational drugs within 30 days or 5 half-lives before Visit 1 (Day 1), whichever is longer.

22. 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 during the screening period.

24. A severe lupus flare within the 6 months prior to screening defined as increased disease activity requiring an increased or added dose of corticosteroids greater than 0.5 mg/kg and/or the addition of a new immunosuppressive drug to control the increased disease activity.

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.

Exclusion Criteria:

1. The participant elects to withdraw consent from all future study activities, including follow-up.

2. The participant is "lost to follow-up" (i.e., no further follow-up is possible because attempts to reestablish contact with the participant have failed).

3. The participant dies.

4. The Investigator no longer believes participation is in the best interest of the participant.

5. The participant is unable to titrate up to and tolerate the minimum ACE inhibitor dose of 20 mg daily for any reason.

6. The participant is unable to demonstrate a minimum compliance rate of 75% (based on the returned pill count) at Visits 2.0, 2.1 and 3.0 in order to titrate up to the next dose level of study drug.

7. The participant experiences a disease flare necessitating increased doses of corticosteroids and/or changes in immunosuppressive medications between Screening and the FIMR Visit 1.1.