Memantine for Cognitive Impairment in SLE

(ClearMEMory Trial)

Not currently recruiting at 2 trial locations

Overseen By Jillian P Rhoads, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Vanderbilt University Medical Center

Must not be taking: Opioids, Antidepressants, Stimulants, others

Disqualifiers: Severe psychiatric disease, Pregnancy, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether memantine, a drug, can alleviate cognitive issues in individuals with Systemic Lupus Erythematosus (SLE), a condition where the immune system attacks its own tissues. Researchers aim to determine if memantine can safely and effectively reduce cognitive problems, such as memory and thinking difficulties, in a specific group of SLE patients. Participants will take either memantine or a placebo (a pill with no active drug) over a 14-week period. Eligible participants are those diagnosed with SLE who experience psychiatric symptoms and have noticeable memory or thinking difficulties. As a Phase 2 trial, this study measures how well memantine works in an initial, smaller group, offering participants a chance to contribute to important research.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot have changed medications that affect mood or cognition in the last 4 weeks. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that memantine is likely to be safe for humans?

Research shows that memantine, the treatment under study, has been safely used in conditions like Alzheimer's disease. Patients generally tolerate memantine well, with common side effects such as dizziness and headaches, while serious side effects remain rare. Studies involving people with Systemic Lupus Erythematosus (SLE) have not shown major safety issues either. This study aims to determine if memantine can help with thinking and memory problems in people with SLE. Although full results are not yet available, previous studies have not reported major safety concerns, suggesting that memantine is likely safe for participants in this new study. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for SLE?

Unlike the standard treatments for cognitive impairment in systemic lupus erythematosus (SLE), which primarily focus on managing symptoms of SLE itself, memantine is unique because it specifically targets the brain's NMDA receptors. This mechanism of action is different because NMDA receptors are involved in cognitive processes, so memantine has the potential to directly improve cognitive function. Researchers are excited about memantine because it could offer a more targeted approach to enhancing cognition in SLE patients, possibly leading to better outcomes than current therapies that don't directly address cognitive impairment.

What evidence suggests that memantine might be an effective treatment for cognitive impairment in SLE?

Research shows that memantine, a drug typically used for Alzheimer's disease, is being studied in this trial to assess its potential benefits for memory and thinking problems in people with systemic lupus erythematosus (SLE). Participants will receive either memantine or a placebo to evaluate its effectiveness. Although early studies have not found significant improvements in thinking skills for SLE patients, researchers are interested in memantine because it affects certain brain receptors important for brain function. This might help with memory and thinking issues in SLE. More research is needed to determine its effectiveness for this condition. ^{1 2 4 5 6}

Who Is on the Research Team?

Leslie J Crofford, MD

Principal Investigator

Professor of Medicine - Rheumatology

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

I have reported symptoms of psychiatric issues related to lupus.

Score ≤ 85 on the RBANS total index (≤ 1 SD below the normative mean of 100)

Meet American College of Rheumatology (ACR) criteria for SLE

Exclusion Criteria

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

Inability or refusal to give informed consent for any reason including a diagnosis of dementia or significant cognitive impairment

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either memantine or placebo with dose escalation over 6 weeks, followed by a stable dose for an additional 6 weeks

12 weeks

Multiple visits for dose adjustments and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Memantine
• Placebo

Trial Overview 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.

How Is the Trial Designed?

Group I: Memantine Experimental Treatment 1 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: Placebo Placebo Group 1 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.

Memantine is already approved in European Union, United States for the following indications:

Approved in European Union as Ebixa for:

• Alzheimer's disease

Approved in United States as Namenda for:

• Moderate to severe Alzheimer's disease

Approved in United States as Namenda XR for:

• Moderate to severe Alzheimer's disease

Approved in United States as Namzaric for:

• Moderate to severe Alzheimer's disease

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

Evergreen Therapeutics, Inc.

Industry Sponsor

Trials

5

Recruited

650+

The University of Texas Health Science Center, Houston

Collaborator

Trials

974

Recruited

361,000+

The Cleveland Clinic

Collaborator

Trials

1,072

Recruited

1,377,000+

Kleberg Foundation

Collaborator

Trials

1

Recruited

80+

Published Research Related to This Trial

Memantine is an NMDA receptor antagonist that provides neuroprotective effects by reducing glutamate overstimulation, making it effective for treating moderate to severe Alzheimer's dementia without the adverse effects commonly seen with stronger antagonists.

It is the first drug approved for Alzheimer's treatment in both Europe and the United States, and ongoing research is exploring its potential benefits in earlier stages of Alzheimer's and other types of dementia, particularly when used in combination with cholinesterase inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The clinical relevance of memantine use]. Sobów, T.[2013]

Memantine is an uncompetitive NMDA receptor antagonist that helps reduce glutamatergic excitotoxicity, showing modest improvement in clinical symptoms and potentially slowing disease progression in moderate-to-severe Alzheimer's disease and other forms of dementia.

Unlike cholinesterase inhibitors, which only provide symptomatic relief, memantine has been effective in severe stages of dementia and is the first drug to completely eliminate pendular nystagmus in multiple sclerosis patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Memantine: pharmacological properties and clinical uses. Kumar, S.[2013]

Cognitive impairment was found in 21% of patients with systemic lupus erythematosus (SLE), significantly higher than the 4% observed in both rheumatoid arthritis patients and healthy controls, indicating a notable risk for cognitive issues in SLE.

The study suggests that cognitive impairment in SLE patients can occur even without clinically overt neuropsychiatric symptoms and is more prevalent in those with active disease and those using corticosteroids, highlighting the need for careful monitoring of cognitive function in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive impairment in patients with systemic lupus erythematosus. Hanly, JG., Fisk, JD., Sherwood, G., et al.[2006]

Memantine is the first clinically useful NMDA inhibitor for dementia, showing significant improvements in cognitive and functional assessments, although its efficacy can vary across different trials.

As a selective NMDA receptor antagonist, memantine works by partially blocking glutamatergic neurotransmission, which may help delay dementia progression, but it has not been directly compared to acetylcholinesterase inhibitors in controlled studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug forecast: memantine, prototype of a new approach to treatment of dementia. Guay, DR.[2006]

In a study of 43 patients with systemic lupus erythematosus (SLE) without major neuropsychiatric syndromes, only 14% had elevated levels of anti-NR2 antibodies, which was not significantly different from the 7.4% found in healthy controls.

There was no association between elevated anti-NR2 levels and cognitive or memory impairments, nor with depressive symptoms, suggesting that these antibodies are unlikely to contribute to cognitive dysfunction in SLE patients without a history of neuropsychiatric issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibodies against N-methyl-D-aspartate receptors in patients with systemic lupus erythematosus without major neuropsychiatric syndromes. Kozora, E., West, SG., Maier, SF., et al.[2021]

Memantine hydrochloride, an NMDA antagonist, was approved for the treatment of moderately severe-to-severe Alzheimer's disease in the EU, with marketing authorization expected in 2002, indicating its efficacy in managing this condition.

The drug is also being explored for various other conditions, including neuropathic pain and ocular diseases, showcasing its potential versatility beyond dementia treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Memantine. Merz. Kilpatrick, GJ., Tilbrook, GS.[2013]

In a study using mice that produce anti-DNA antibodies similar to those found in lupus patients, cognitive impairment and neuronal death occurred only after the blood-brain barrier was compromised, highlighting the role of the immune system in cognitive decline without direct CNS inflammation.

The NMDA receptor antagonist memantine was effective in preventing neuronal damage when administered before the triggering of the immune response, suggesting that NMDA receptor antagonists could be a potential new treatment strategy for cognitive dysfunction in lupus patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognition and immunity; antibody impairs memory. Kowal, C., DeGiorgio, LA., Nakaoka, T., et al.[2022]

Cognitive impairment in MRL/lpr mice, a model for systemic lupus erythematosus (SLE), was linked to high levels of anti-NR2a/b antibodies and inflammatory factors, indicating a potential autoimmune mechanism affecting brain function.

The NMDA receptor antagonist memantine improved cell proliferation and reduced inflammatory markers in micro-vascular endothelial cells, suggesting it may help mitigate cognitive deficits associated with SLE by modulating inflammatory responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive impairment of MRL mice is related to NMDA receptor-mediated inflammatory response and production of adhesion molecules in MRL/lpr mice-derived micro-vascular endothelial cells. Guan, X., Wang, J.[2023]

Memantine is an NMDA receptor antagonist that has shown neuroprotective and cognition-enhancing effects in animal models, and it has been clinically effective in improving cognitive performance in patients with Alzheimer's disease and vascular dementia.

Clinical trials have demonstrated that memantine is well-tolerated, with a low incidence of adverse events, making it a safe option for treating moderately severe to severe Alzheimer's disease, leading to its approval in both Europe and the US.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Memantine hydrochloride: pharmacological and clinical profile. Möbius, HJ., Stöffler, A., Graham, SM.[2017]

In a study using MRL/lpr mice, memantine (MEM) showed some improvement in exploratory behavior, suggesting a potential role in addressing neuropsychiatric symptoms associated with systemic lupus erythematosus (SLE), but it did not prevent the overall development of CNS SLE-like symptoms.

Chronic treatment with MEM negatively impacted body growth and spontaneous activity in control mice, indicating that its effects are complex and may not solely target autoimmunity mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of prolonged treatment with memantine in the MRL model of CNS lupus. Marcinko, K., Parsons, T., Lerch, JP., et al.[2021]

In a 12-week trial involving 51 patients with systemic lupus erythematosus (SLE), memantine did not show significant overall improvement in cognitive performance compared to a placebo, based on various neuropsychological assessments.

However, there was a notable improvement in the Controlled Oral Word Association Test for the memantine group at 12 weeks, suggesting a potential specific benefit in verbal fluency, although this was not observed in the broader cognitive assessments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Memantine in systemic lupus erythematosus: a randomized, double-blind placebo-controlled trial. Petri, M., Naqibuddin, M., Sampedro, M., et al.[2021]

The case describes a man with systemic lupus erythematosus (SLE) who exhibited rare neurological symptoms, including pachymeningitis and encephalitis, which responded positively to immunosuppressive treatment, highlighting the potential for effective management of neuropsychiatric manifestations of SLE.

Cerebrospinal fluid analysis revealed significantly elevated protein levels and a white cell count indicative of inflammation, and the patient's condition improved with a combination of antibiotics and corticosteroids, demonstrating the importance of timely and appropriate treatment in complex SLE cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An unusual case of inflammatory meningitis in a young man with systemic lupus erythematosus. Smith, R., Hadjivassiliou, M., Hoggard, N., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3153605/

Memantine in Systemic Lupus Erythematosus: A Randomized ... In this first clinical trial of memantine in SLE, patients treated with memantine did not exhibit significant improvement in cognitive performance compared to ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0049017211000333

Memantine in Systemic Lupus Erythematosus Cognitive impairment affects up to 80% of systemic lupus erythematosus (SLE) patients within 10 years of diagnosis. Memantine, a seronergic receptor and ...

3. news.vumc.org news.vumc.org/2022/10/06/vumc-to-test-whether-alzheimers-drug-can-ease-lupus-symptoms/

VUMC to test whether Alzheimer's drug can ease lupus ... ... memantine, can improve cognitive symptoms associated with systemic lupus erythematosus (SLE), an autoimmune disease. The external licensing ...

4. ctv.veeva.com ctv.veeva.com/study/memantine-for-the-treatment-of-cognitive-impairment-in-systemic-lupus-erythematosus

Memantine for the Treatment of Cognitive Impairment in ... The objective of this study is to evaluate the safety, tolerability and efficacy of memantine, an NMDA receptor antagonist, in a precise patient ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2762361/

Memantine: a review of studies into its safety and efficacy in ... This review covers key studies of memantine's safety and efficacy in treating moderate to severe AD. It also covers current research into other dementias.

6. withpower.com withpower.com/trial/phase-3-lupus-erythematosus-systemic-7-2018-221b7

Memantine for Cognitive Impairment in SLE This trial is testing memantine, a drug that blocks certain brain receptors, in people with Systemic Lupus Erythematosus (SLE) who have a specific genetic ...