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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
Sponsor:
Collaborator:
Forest Laboratories
Information provided by:
Johns Hopkins University

Tracking Information
First Submitted Date  ICMJE September 13, 2005
First Posted Date  ICMJE September 16, 2005
Last Update Posted Date March 7, 2008
Study Start Date  ICMJE March 2006
Actual Primary Completion Date May 2007   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 5, 2008)
Change in ANAM, Version 3.11 [ Time Frame: 12 Weeks ]
Original Primary Outcome Measures  ICMJE
 (submitted: September 13, 2005)
  • Change in ANAM, Version 3.11
  • Change in ACR Neuropsychological Battery
  • Change in Anti-glutamate receptor antibody ELISA
  • Change in SELENA SLEDAI score
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Memantine in Systemic Lupus Erythematosus
Official Title  ICMJE Memantine in Systemic Lupus Erythematosus
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.
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  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Systemic Lupus Erythematosus
Intervention  ICMJE
  • Drug: Memantine
    Dispensing initially 5 mg. Dose Increased by 5 mg weekly to 20 mg/d final dose by week 4.
    Other Name: Namenda
  • Drug: Placebo
    Dispensing initially 5 mg. Dose Increased by 5 mg weekly to 20 mg/d final dose by week 4
Study Arms  ICMJE
  • Active Comparator: 1
    Intervention: Drug: Memantine
  • Placebo Comparator: 2
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 5, 2008)
61
Original Enrollment  ICMJE
 (submitted: September 13, 2005)
60
Actual Study Completion Date  ICMJE May 2007
Actual Primary Completion Date May 2007   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00181298
Other Study ID Numbers  ICMJE NAM-MD-20
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Dr. Michelle Petri, Johns Hopkins University
Study Sponsor  ICMJE Johns Hopkins University
Collaborators  ICMJE Forest Laboratories
Investigators  ICMJE
Principal Investigator: Michelle Petri, M.D., M.P.H. Johns Hopkins University
PRS Account Johns Hopkins University
Verification Date March 2008

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP