Memantine for Corticosteroid-Induced Mood and Declarative Memory Changes
Condition: Physiological Effects of Drugs
Study type: Interventional
Phase: Phase 4

Summary: 
      The purpose of this research is to determine if patients on corticosteroids who are given
      memantine will show improvement in memory compared to those receiving placebo (an inactive
      substance). This research also seeks to determine if such patients, when given memantine,
      will experience improvement in manic/hypomanic symptoms (feelings of agitation,
      overexcitement, or hyperactivity) and/or depressive symptoms. Subjects will be randomized to
      a crossover trial of memantine and placebo for 8 weeks, followed by a 4 week washout and then
      8 more weeks of the study medication. Memantine and placebo will start at 5 mg/day for one
      week, increased to 5 mg twice a day in the second week. During the third week patients will
      take 10 mg in the morning and 5 mg in the evening. At weeks 4-8, patients will take 10 mg
      twice a day. One 8 week course of study medication will be memantine and the other 8 week
      course of study medication will be placebo, both assigned in a random fashion.
    

Detailed description: 
      Twenty (20) outpatients with pulmonary (e.g. asthma), rheumatic (e.g. rheumatoid arthritis,
      dermatomyositis) illnesses or renal transplants (all populations we have used in prior
      clinical trials) receiving a course of prednisone or other corticosteroid for at least 12
      weeks will be enrolled. To participate, patients must be between the ages of 18 and 70 and
      taking at least 5 mg/day of prednisone, or a prednisone equivalent, for at least 3 months and
      with the expectation that they will be continuing such treatment at the same dose for at
      least 20 additional weeks. At baseline, the research assistant or study doctor will ask
      patients about their health, any prior corticosteroid therapy and other medications patients
      may take for any health problems, medication allergies, and any surgical procedures or
      cognitive impairments they may have. Patients will have memory tests and answer questions
      about their mood, sleep, appetite, and daily activities.

      The subjects will be randomized to a crossover trial of memantine and placebo for 8 weeks
      followed by a 4 week washout and then 8 more weeks of study drug. Memantine will be started
      at 5 mg/day for 1 week, increased to 5 mg BID in the second week, 10 mg QAM and 5 mg QHS the
      next week and to 10 mg BID in weeks 4-8 as directed in the package insert. One 8 week course
      will be memantine and the other placebo assigned in a random fashion. Measures of memory will
      be compared within subjects at baseline, week 4, week 8, week 12 (beginning of second course
      of study drug), week 16 and week 20 (exit). At weeks 2 and 14, participants will be given 3
      questionnaires that will measure mood; medication management will be conducted during these
      assessments. Each visit, including baseline, should take approximately one and a half hours.

      Detailed Experimental: Baseline measures of mood will be assessed with the Activation
      subscale of the Internal State Scale (ISS) (primary measure), Hamilton Depression Rating
      Scale (17-item version), and Young Mania Rating Scale (YMRS). Cognition will be assessed with
      the HVLT-R (primary measure), and STROOP color word task. The subjects will be given
      memantine or identical appearing placebo as described above. Reductions in dosage will be
      allowed should clinically significant side effects emerge based on the judgment of a blinded
      psychiatrist. The above cognitive measures will be administered at each assessment visit (8
      total); during the assessments at week 2 and week 14 patients will also be given 3 mood
      questionnaires. Each visit will be approximately an hour and half in length. The RA doing
      assessments will be blinded at all times. Alternative but equivalent versions of the HVLT-R
      will be given to minimize practice or learning effects. Current and cumulative corticosteroid
      dose (mg each day X number of days) will be determined and recorded.

      In the case of missing data we will use the last observation carried forward. In our
      lamotrigine study in a similar population, we found a change in the total words recalled on a
      word list and on the Stroop. Assuming a similar change with memantine and using double-sided,
      paired t-tests, we could detect a difference with a change in the placebo group with
      participants on the HVLT-R and with participants on the STROOP. Thus, although this is
      primarily a pilot study to obtain effect sizes for future, larger trials funded by NIH, it
      should have power to detect clinically meaningful differences between medication and placebo.
    

Intervention name(s): Memantine
Intervention type(s): Drug
Intervention MeSH terms: Memantine
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Double
Primary purpose: Treatment
Keywords: corticosteroid; prednisone; memantine; Patients who are taking a corticosteroid for a; pulmonary illness; rheumatic illness; kidney transplant