Memantine in Systemic Lupus Erythematosus

Sponsor

Johns Hopkins University (Other)

Overall Status

Completed

CT.gov ID

NCT00181298

Collaborator

Forest Laboratories (Industry)

Enrollment

Location

Arms

Duration (Months)

4.4

Patients Per Site Per Month

Study Details

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	N/A

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

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 :

Mar 1, 2006

Actual Primary Completion Date :

May 1, 2007

Actual Study Completion Date :

May 1, 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 Names: 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

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 Names:

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

Change in ANAM, Version 3.11 [12 Weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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