Memantine for the Treatment of Cognitive Impairment in Systemic Lupus Erythematosus

NCT ID: NCT03527472

Last Updated: 2025-08-29

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 111 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-08-23
• Study Completion Date: 2025-12-31

Brief Summary

A phenome-wide association study (PheWAS) identified an association between a variant in the human gene for the N2A subunit of the N-methyl-D-aspartate (NMDA) receptor, GRIN2A, and Systemic Lupus Erythematosus (SLE). A single nucleotide polymorphism (SNP) in this gene encodes for increased NMDA receptor activity. Based on the potential function of the associated SNP and published literature, alterations in SNP function signaling may underlie a cluster of symptoms. The objective of this study is to evaluate the safety, tolerability and efficacy of memantine, an NMDA receptor antagonist, in a precise patient subset with SLE. Participants will complete a full 14-week clinical trial, receiving either memantine or a placebo. Participants' blood will be drawn to test for various antibodies as well as organ function. Patients' urine will also be collected to assess organ function and pregnancy for females at a number of specific time points. The overall goal is to develop a safe and inexpensive therapeutic approach to reduce debilitating cognitive symptoms in a precisely selected SLE sub-population.

Conditions

Lupus Erythematosus, Systemic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Memantine

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 Type: EXPERIMENTAL

Memantine

Intervention Type: DRUG

Memantine is an FDA-approved drug for the treatment of Alzheimer's disease.

Placebo

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

The placebo will match the study drug in appearance, dose, and frequency. It will not contain any active drug (memantine).

Interventions

Memantine

Memantine is an FDA-approved drug for the treatment of Alzheimer's disease.

Intervention Type: DRUG

Placebo

The placebo will match the study drug in appearance, dose, and frequency. It will not contain any active drug (memantine).

Intervention Type: DRUG

Other Intervention Names

Namenda

Eligibility Criteria

Inclusion Criteria

1. Meet American College of Rheumatology (ACR) criteria for SLE

2. Report NPSLE symptoms on the screening survey recommended by EULAR guideline but limited to the psychiatric manifestations questions

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

Exclusion Criteria

1. Male and female subjects <18 or >60 years

2. Change in medication that may affect mood or cognition including prednisone, antidepressant medications, or stimulants within the last 4 weeks

3. Regular (daily) use of opioids or other drugs of abuse including heavy alcohol or marijuana use

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

5. Severe psychiatric disease including schizophrenia, psychosis, suicidal depression

6. Other factors which in the opinion of the investigator could potentially impact the study outcomes (e.g., underlying disease, medications, history)* or prevent the participant from completing the protocol (poor compliance or unpredictable schedule)

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

8. Patients who are pregnant

9. Patients who are enrolled in other investigational drug studies

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Evergreen Therapeutics, Inc.

INDUSTRY

Sponsor Role: collaborator

The University of Texas Health Science Center, Houston

OTHER

Sponsor Role: collaborator

The Cleveland Clinic

OTHER

Sponsor Role: collaborator

Vanderbilt University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Leslie Crofford

Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Leslie J Crofford, MD

Role: PRINCIPAL_INVESTIGATOR

Professor of Medicine - Rheumatology

Locations

The Cleveland Clinic

Cleveland, Ohio, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

The University of Texas Health Science Center, Houston

Houston, Texas, United States

Countries

United States

Provided Documents

Document Type: Informed Consent Form

View Document

Other Identifiers

180256

Identifier Type: -

Identifier Source: org_study_id