Memantine in Systemic Lupus Erythematosus

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

Study Description

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	Phase
Systemic Lupus Erythematosus	Drug: Memantine; Drug: Placebo	Not Applicable

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 Design

• 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
• Actual Primary Completion Date: May 2007
• Actual Study Completion Date: May 2007

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

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

Investigators

• Principal Investigator: Michelle Petri, M.D., M.P.H.; Johns Hopkins University

More Information

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

Keywords provided by Johns Hopkins University:

Memantine; SLE; Anti NR2; ANAM; Cognitive functioning

Additional relevant MeSH terms:

Lupus Erythematosus, Systemic; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Memantine; 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