Systemic lupus erythematosus
Memantine in Systemic Lupus Erythematosus: A Randomized, Double-Blind Placebo-Controlled Trial

https://doi.org/10.1016/j.semarthrit.2011.02.005Get rights and content

Objectives

Cognitive impairment affects up to 80% of systemic lupus erythematosus (SLE) patients within 10 years of diagnosis. Memantine, a seronergic receptor and nicotine acetylcholine receptor antagonist, acts on the glutamatergic system through the NMDA receptor and is used to treat dementia. We investigated whether it had benefit for SLE cognitive impairment.

Methods

A randomized double-blind, placebo-controlled single-center 12-week trial of memantine titrated to 20 mg/d was performed, using a 2:1 randomization ratio, in 51 SLE patients. The primary outcome measures were change in the Automated Neuropsychological Assessment Metrics throughput scores at 12 weeks.

Results

There were no statistically significant differences between treatment groups or change from baseline in any of the Automated Neuropsychological Assessment Metrics throughput scores at 6 or 12 weeks. For the American College of Rheumatology cognitive battery, the only statistically significant findings were for the Controlled Oral Word Association Test—S words at 6 and 12 weeks. At 12 weeks, the memantine group exhibited greater improvement compared with the placebo group (3.6 ± 1.8 vs 0.5 ± 3.8 words, P = 0.03). In a subset analysis limited to patients that scored ≥1 standard deviation below normal controls at baseline, no significant differences between treatment groups were found.

Conclusions

In this first clinical trial of memantine in SLE, patients treated with memantine did not exhibit significant improvement in cognitive performance compared with the placebo group, regardless of the degree of impairment at baseline, with the exception of controlled oral word association.

Section snippets

Methods

The study was approved by The Johns Hopkins University School of Medicine Institutional Review Board and was registered with clinicaltrials.gov (clinical trials.gov identifier NCT00181298). All patients gave signed informed consent.

The study was a single-center (Hopkins Lupus Center), double-blind, randomized, placebo-controlled phase 2 trial. The randomization allocation was 2:1 memantine to placebo. Enrollment took place between March 2006 and February 2007 at the Johns Hopkins Hospital. The

Results

The consort diagram is shown in Figure 1. One patient was found to be ineligible after randomization (due to renal dysfunction). Two patients withdrew from the study after 1 month. Demographic and clinical characteristics of the 51 patients that completed the baseline visit are presented in Table 1. The memantine and placebo groups did not differ in demographic characteristics, or in the 11 ACR criteria. The only historical clinical characteristics that significantly differed between treatment

Discussion

This trial is the first randomized trial for mild cognitive impairment in SLE. As such, important lessons were learned. One unexpected finding was that 12 patients (24%) with cognitive impairment by self-report and physician targeted questioning using EULAR guidelines [28] did not score at least a 1 SD below normative data on at least 1 ANAM test and 6 (12%) patients did not on at least 1 ACR cognitive test. The ACR Neuropsychiatric Battery appears to be more sensitive than ANAM in detecting

Conclusion

In conclusion, the trial was slightly underpowered, because 12% of patients with self-reported and physician-confirmed cognitive impairment did not exhibit significant impairment at baseline on any of the cognitive measures. Possible improvement was seen in 2 cognitive domains: continuous performance and simple reaction time, with significant improvement in 1 domain: oral word association. These results can be used to select appropriate patients and to power future clinical trials for cognitive

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  • Cited by (0)

    This study was supported in part by Forest Laboratories, Inc., NIH RO1 AR049125, and by Grant UL1 RR 025005 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) and NIH Roadmap for Medical Research, and its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH.

    The authors have no conflicts of interest to disclose.

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