Memantine for the Treatment of Cognitive Impairment in Systemic Lupus Erythematosus

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years - 70 Years
Gender	All

More Inclusion & Exclusion 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

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT03527472
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 2
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Vanderbilt University Medical Center
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Leslie J Crofford, MD
Principal Investigator Affiliation	Professor of Medicine - Rheumatology
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other, Industry
Overall Status	Recruiting
Countries	United States
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Lupus Erythematosus, Systemic

Arms & Interventions

Arms

Experimental: 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.

Placebo Comparator: 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.

Interventions

Drug: - Memantine

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

Drug: - Placebo

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

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

The Cleveland Clinic, Cleveland, Ohio

Status

Recruiting

Address

The Cleveland Clinic

Cleveland, Ohio, 44195

Site Contact

Andy Wiecek

[email protected]

216-444-7722

Vanderbilt University Medical Center, Nashville, Tennessee

Status