Memantine in Systemic Lupus Erythematosus

This study has been completed.
Sponsor:
Collaborator:
Forest Laboratories
Information provided by:
Johns Hopkins University
ClinicalTrials.gov Identifier:
NCT00181298
First received: September 13, 2005
Last updated: March 5, 2008
Last verified: March 2008
  Purpose

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 Intervention
Systemic Lupus Erythematosus
Drug: Memantine
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Memantine in Systemic Lupus Erythematosus

Resource links provided by NLM:


Further study details as provided by Johns Hopkins University:

Primary Outcome Measures:
  • Change in ANAM, Version 3.11 [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]

Enrollment: 61
Study Start Date: March 2006
Study Completion Date: May 2007
Primary Completion Date: May 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00181298

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

No publications provided

Responsible Party: Dr. Michelle Petri, Johns Hopkins University
ClinicalTrials.gov Identifier: NCT00181298     History of Changes
Other Study ID Numbers: NAM-MD-20
Study First Received: September 13, 2005
Last Updated: March 5, 2008
Health Authority: United States: Food and Drug Administration

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
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 23, 2014