What is the mechanism of action of this treatment?

Common treatments for Systemic Lupus Erythematosus (SLE) include immunosuppressive drugs like cyclophosphamide, mycophenolate, and azathioprine, which work by reducing the activity of the immune system to prevent it from attacking the body's own tissues. Another treatment, hydroxychloroquine, modulates the immune response and has anti-inflammatory properties. Memantine, an NMDA receptor antagonist, is being studied for its potential to reduce cognitive symptoms in SLE by blocking excessive NMDA receptor activity, which can lead to neurotoxicity. These treatments are crucial for SLE patients as they help manage the overactive immune response and reduce inflammation, thereby preventing organ damage and improving quality of life.

What side effects are associated with this type of intervention?

Common treatments for Systemic Lupus Erythematosus (SLE) include immunosuppressive agents like mycophenolate mofetil, cyclophosphamide, and azathioprine. Mycophenolate mofetil can cause nausea, diarrhea, and increased risk of infections. Cyclophosphamide is associated with side effects such as bone marrow suppression, increased risk of infections, and potential bladder toxicity. Azathioprine may lead to bone marrow suppression, liver enzyme elevation, and increased susceptibility to infections. While memantine, an NMDA receptor antagonist, is being studied for cognitive impairment in SLE, its common side effects include dizziness, headache, and confusion. Broadly, SLE treatments often carry risks of immunosuppression and organ-specific toxicities.

What prior FDA approvals exist?

The FDA has approved several treatments for Systemic Lupus Erythematosus (SLE), including belimumab, which is a monoclonal antibody that inhibits B-lymphocyte stimulator (BLyS). Other treatments include immunosuppressive agents like cyclophosphamide and mycophenolate mofetil. However, there are no FDA-approved treatments for SLE that are similar to Memantine, an NMDA receptor antagonist. Current research is exploring the potential of NMDA receptor antagonists like Memantine for treating cognitive impairment in SLE, but these are still under investigation.

What other types of research exist?

Promising alternatives to Memantine for SLE patients include: 1) Anti-GluN2B antibodies, which have shown higher titers in SLE patients with fibromyalgia, suggesting a potential therapeutic target. 2) Laquinimod, an oral immunomodulator studied in multiple sclerosis, which may have applications in SLE due to its anti-inflammatory properties. 3) Mycophenolate mofetil, used in resistant autoimmune conditions like dermatomyositis, which could be repurposed for SLE. These alternatives are based on their mechanisms of action and recent research findings.

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NMDA Receptor Antagonist

Memantine for Cognitive Impairment in SLE (ClearMEMory Trial)

Phase 2

Recruiting

Led By Leslie J Crofford, MD

Research Sponsored by Vanderbilt University Medical Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Must not have

Metabolic derangement defined as liver function tests >3x upper limit of normal or severe renal disease defined as calculated creatinine clearance <30 mL

Male and female subjects <18 or >60 years

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 12 weeks

Summary

This trial is testing memantine, a drug that blocks certain brain receptors, in people with Systemic Lupus Erythematosus (SLE) who have a specific genetic variant. The goal is to see if memantine can safely and effectively reduce cognitive symptoms in these patients. Memantine is used to treat memory and thinking problems and has been investigated for similar issues in SLE patients.

Who is the study for?

This trial is for adults aged 18-60 with Systemic Lupus Erythematosus (SLE) who meet specific criteria and have cognitive symptoms. They must not use heavy drugs or alcohol, have had recent medication changes that affect mood/cognition, severe liver/renal disease, be pregnant, or involved in other drug studies.

What is being tested?

The study tests the safety and effectiveness of Memantine—an NMDA receptor antagonist—against a placebo over 14 weeks to reduce cognitive impairment in SLE patients. It includes blood and urine tests to monitor organ function and pregnancy status.

What are the potential side effects?

Memantine may cause dizziness, headache, confusion, constipation, or tiredness. Since it affects brain chemicals involved in learning and memory, some people might also experience mood changes.

Eligibility Criteria

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My liver tests are more than three times the normal limit or my kidneys work poorly.

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I am younger than 18 or older than 60.

Select...

I haven't changed medications affecting mood or thinking in the last 4 weeks.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 12 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~12 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and 12 weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Repeatable Battery for Assessment of Neuropsychological Status (RBANS) Total Index Score at endpoint (Visit 4)

Secondary study objectives

Beck Depression Inventory

Hospital Anxiety and Depression Scale

Incidence of Treatment-Emergent Adverse Events

+4 more

Side effects data

From 2019 Phase 4 trial • 115 Patients • NCT01902004

23%

Sleepiness/Sedation

10%

Headache

Tension/Inner Unrest

Reduced Salivation

Concentration Difficulties

Diminished Sexual Drive

Asthenia/Lassitude/Increased Fatigability

Constipation

Polyuria/Polydipsia

Orthostatic Dizziness

Nausea/Vomiting

Erectile Dysfunction

Failing Memory

Diarrhea

Increased Duration of Sleep

Reduced Duration of Sleep

Increased Dream Activity

Accomodation Disturbance

Increased Tendancy to Sweating

Weight Gain

Ejaculatory Dysfunction

Micturtion Disturbances

100%

80%

60%

40%

20%

Study treatment Arm

Escitalopram and Placebo

Escitalopram and Memantine

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: MemantineExperimental Treatment1 Intervention

At randomization, subjects will receive 5 mg twice per day for one week. They will escalate their dose to 10 mg twice per day for one week, then 10 mg in the morning and 20 mg at night for one week, and finally 20 mg twice per day for three weeks. Maximum tolerated will be determined at this time and this dose will be continued for an additional six weeks.

Group II: PlaceboPlacebo Group1 Intervention

At randomization, subjects will receive one matching placebo capsule twice per day for one week. They will also take one matching placebo capsule twice per day for the next week (week 2), then one matching placebo capsule in the morning and two capsules at night for one week (week three), and finally two capsules twice per day for three weeks (weeks 4-6). Maximum tolerated number of capsules will be determined at this time and this dose will be continued for an additional six weeks.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Memantine

2006

Completed Phase 4

~1180

0 / 3Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Systemic Lupus Erythematosus (SLE) include immunosuppressive drugs like cyclophosphamide, mycophenolate, and azathioprine, which work by reducing the activity of the immune system to prevent it from attacking the body's own tissues. Another treatment, hydroxychloroquine, modulates the immune response and has anti-inflammatory properties. Memantine, an NMDA receptor antagonist, is being studied for its potential to reduce cognitive symptoms in SLE by blocking excessive NMDA receptor activity, which can lead to neurotoxicity. These treatments are crucial for SLE patients as they help manage the overactive immune response and reduce inflammation, thereby preventing organ damage and improving quality of life.