Memantine for the Treatment of Cognitive Impairment in Systemic Lupus Erythematosus

NCT03527472 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: 180256
• Study Type: interventional
• Target: 111
• Locations: 1 country
• Sites: 3

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

Keywords

cognitive dysfunction; memantine; lupus

Outcome Measures

Primary Outcomes (1)

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

  RBANS is a widely used psychiatric tool that objectively measures cognitive impairment. It is comprised of 12 subtests and takes approximately 30 minutes. For scoring, the RBANS index scores are converted to classifications including Very Superior (130 and above), Superior (120-129), High Average (110-119), Average (90-109), Low Average (80-89), Borderline (70-79), and Extremely Low (69 and below). A score of Extremely Low equates to severe cognitive impairment. The primary outcome measure will be analyzed using ANCOVA controlling for memantine/placebo, baseline RBANS, sex, age, and NMDAR status.

  12 weeks

Secondary Outcomes (7)

• Incidence of Treatment-Emergent Adverse Events

  12 weeks

• Polysymptomatic Distress Scale

  12 weeks

• Beck Depression Inventory

  12 weeks

• Hospital Anxiety and Depression Scale

  12 weeks

• Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2K

  12 weeks

Study Arms (2)

Memantine

EXPERIMENTAL

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.

Drug: Memantine

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Memantine DRUG

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

Also known as: Namenda

Memantine

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Meet American College of Rheumatology (ACR) criteria for SLE
• Report NPSLE symptoms on the screening survey recommended by EULAR guideline but limited to the psychiatric manifestations questions
• Score ≤ 85 on the RBANS total index (≤ 1 SD below the normative mean of 100)

You may not qualify if:

• Male and female subjects \<18 or \>60 years
• Change in medication that may affect mood or cognition including prednisone, antidepressant medications, or stimulants within the last 4 weeks
• Regular (daily) use of opioids or other drugs of abuse including heavy alcohol or marijuana use
• Metabolic derangement defined as liver function tests \>3x upper limit of normal or severe renal disease defined as calculated creatinine clearance \<30 mL
• Severe psychiatric disease including schizophrenia, psychosis, suicidal depression
• 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)
• Inability or refusal to give informed consent for any reason including a diagnosis of dementia or significant cognitive impairment\*\*
• Patients who are pregnant
• Patients who are enrolled in other investigational drug studies

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead
• Evergreen Therapeutics, Inc.: collaborator
• The University of Texas Health Science Center, Houston: collaborator
• The Cleveland Clinic: collaborator

Study Sites (3)

The Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

The University of Texas Health Science Center, Houston

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Lupus Erythematosus, Systemic; Cognitive Dysfunction

Interventions

Memantine

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Amantadine; Adamantane; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Leslie J Crofford, MD

  Professor of Medicine - Rheumatology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Model Details: Double-blind, randomized, placebo-controlled

Study Record Dates

• First Submitted: May 3, 2018
• First Posted: May 17, 2018
• Study Start: August 23, 2018
• Primary Completion: February 28, 2026
• Study Completion: February 28, 2026
• Last Updated: April 22, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)