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Memantine in Systemic Lupus Erythematosus

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ClinicalTrials.gov Identifier: NCT00181298
Recruitment Status : Completed
First Posted : September 16, 2005
Last Update Posted : March 7, 2008
Forest Laboratories
Information provided by:
Johns Hopkins University

Brief Summary:
Neuropsychiatric manifestations of Systemic Lupus Erythematosus (NPSLE) are both common and an important source of morbidity. Of the case definitions for NPSLE syndromes that have recently been developed, cognitive dysfunction appears to be the most prevalent. A novel mechanism is that a subset of SLE patients with cognitive dysfunction have antibodies in the NR2 glutamate receptor. We propose, in a double -blind placebo-controlled trial, to determine whether SLE patients, with or without the NR2 glutamate receptor antibody, have significant improvement using memantine, an inhibitor of the NMDA receptor.

Condition or disease Intervention/treatment
Systemic Lupus Erythematosus Drug: Memantine Drug: Placebo

Detailed Description:

Patients with SLE frequently report cognitive and memory problems and many studies have documented significant cognitive deficits with traditional neuropsychological test batteries. Many traditional neuropsychological tests are unsuitable for repeated measures over short intervals caused by expected improvement due to test-retest or practice effects. We will utilize an automated battery (ANAM) of cognitive function tests at baseline, 6 weeks, and 12 weeks, as the outcome measure.

Betty Diamond M.D. and colleagues demonstrated that a subset of lupus anti-DNA antibodies cross-reacts with the NR2 glutamate receptor in patients with SLE. Glutamate receptors can display altered expression in major psychosis and over-stimulation of NR2 can cause excitotoxic neuron death through excessive entry of calcium into cells. Thus, antibody reactivity with NR2a or NR2b may not only serve as a marker for CNS disease in SLE but may also be neuropathogenic mechanism for some of the non-focal CNS disturbances in SLE.

Memantine is a low- to moderate-affinity, noncompetitive N-methyl-D-asparate (NMDA) receptor that represents the first member of a new class of medications showing clinical benefit and good tolerability in Alzheimer's Disease. Because of our anecdotal experience with some SLE patients with cognitive impairment improving with donepezil therapy, an approved Alzheimer's Disease therapy, and because of the known association of cognitive impairment in SLE with anti-NR2 glutamate (NMDA) receptor antibodies, we hypothesize that memantine will have benefit for cognitive dysfunction in SLE.

We believe that computerized cognitive function batteries (ANAM) can be used in clinical trials of cognitive impairment, with the benefit of efficiency, immediate results, and less patient time. However, because this is the first clinical trial of this kind in SLE, we will also use the formal American College of Rheumatology neuropsychiatric battery, as well

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 61 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Memantine in Systemic Lupus Erythematosus
Study Start Date : March 2006
Primary Completion Date : May 2007
Study Completion Date : May 2007

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lupus
U.S. FDA Resources

Arm Intervention/treatment
Active Comparator: 1 Drug: Memantine
Dispensing initially 5 mg. Dose Increased by 5 mg weekly to 20 mg/d final dose by week 4.
Other Name: Namenda
Placebo Comparator: 2 Drug: Placebo
Dispensing initially 5 mg. Dose Increased by 5 mg weekly to 20 mg/d final dose by week 4

Primary Outcome Measures :
  1. Change in ANAM, Version 3.11 [ Time Frame: 12 Weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Clinical diagnosis of SLE
  • Self-reported cognitive impairment

Exclusion Criteria:

  • Age < 18 years.
  • History of non-compliance
  • Pregnancy
  • Liver or renal insufficiency/failure (calculated creatinine clearance < 50 cc/min)
  • Severe SLE flare in the last 6 weeks (defined as SLEDAI > 12 points)
  • Recent (within 4 weeks) change in any medication relevant to cognitive function, including prednisone, anti-depressants, medications for insomnia, narcotic medications, attention deficit disorder medications
  • Current alcohol or illicit drug abuse
  • Current use of Namenda, Aricept, Provigil

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00181298

United States, Maryland
Johns Hopkins Lupus Center, 1830 East Monument Street, Suite 7500
Baltimore, Maryland, United States, 21205
Sponsors and Collaborators
Johns Hopkins University
Forest Laboratories
Principal Investigator: Michelle Petri, M.D., M.P.H. Johns Hopkins University

Responsible Party: Dr. Michelle Petri, Johns Hopkins University
ClinicalTrials.gov Identifier: NCT00181298     History of Changes
Other Study ID Numbers: NAM-MD-20
First Posted: September 16, 2005    Key Record Dates
Last Update Posted: March 7, 2008
Last Verified: March 2008

Keywords provided by Johns Hopkins University:
Anti NR2
Cognitive functioning

Additional relevant MeSH terms:
Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Antiparkinson Agents
Anti-Dyskinesia Agents
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents