Memantine in Systemic Lupus Erythematosus

Systemic Lupus Erythematosus Clinical Trial

Official title:

Memantine in Systemic Lupus Erythematosus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00181298
• Other study ID #: NAM-MD-20
• Status: Completed
• Phase: N/A
• First received: September 13, 2005
• Last updated: March 5, 2008
• Start date: March 2006
• Est. completion date: May 2007

Study information

• Verified date: March 2008
• Source: Johns Hopkins University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 61
• Est. completion date: May 2007
• Est. primary completion date: May 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus

Intervention

Drug:
• Memantine
Dispensing initially 5 mg. Dose Increased by 5 mg weekly to 20 mg/d final dose by week 4.
• Placebo
Dispensing initially 5 mg. Dose Increased by 5 mg weekly to 20 mg/d final dose by week 4

Locations

Country	Name	City	State
United States	Johns Hopkins Lupus Center, 1830 East Monument Street, Suite 7500	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Johns Hopkins University	Forest Laboratories

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in ANAM, Version 3.11		12 Weeks	No