Attenuation of Corticosteroid Induced Hippocampal Changes
Condition: Organic Memory Impairment
Study type: Interventional
Phase: Phase 4

Summary: 
      The purpose of the study is to determine if an investigational drug called memantine,used
      here as add-on therapy, is associated with improvements in memory, mood and asthma symptoms.
      We will also examine changes in the brain by taking images or pictures using an MRI/MRS.
    

Detailed description: 
      A total of 50 outpatients receiving chronic oral corticosteroid therapy will be enrolled in a
      52-week randomized, double-blind, placebo-controlled, crossover trial of memantine.
      Participant will receive either memantine or a placebo for 24 weeks. They have an equal
      chance of receiving memantine or placebo. After 24 weeks they will discontinue all study
      medication for 4 weeks. This process will be repeated one additional time in the study and
      the participant will crossed-over to either memantine or placebo, whichever the participant
      did not receive before, so they will have taken both placebo and memantine during one of
      these courses.

      Randomization will be stratified by prednisone dose of < 20 mg/day vs. ≥ 20 mg/day. Memantine
      or placebo starting at 5 milligrams once a day, increased to 5 milligrams twice a day (10
      total) at week 2, 15 milligrams total at week 3, and 20 milligrams total from weeks 4-24
      unless side effects require the study doctor to increase the initial doses slower than
      described above or reduce the dose. This same process will be repeated at week 28 after the
      participant have been completely off of study medication for 4 weeks. Structural MRI and
      1HMRS will be obtained at baseline and weeks 24 and 52 (after memantine and placebo).

      The clinician version of the structured Clinical Interview for DSM-IV (SCID) is a brief
      structured interview for major Axis I disorders in DSM-IV including major depressive
      disorder, dysthymic disorder, bipolar disorders, psychotic disorders, anxiety disorders,
      eating disorders, and alcohol and substance abuse/dependence. This will be given at baseline
      to screen for illnesses with CNS involvement or cognitive impairment. Blood draws will be
      performed at baseline to assess insulin and fasting glucose levels.

      Each participant will then return for follow-up appointments as scheduled and repeat outcome
      measures. Pill counts will be conducted, and a list of current medications and doses will be
      obtained at each visit. Participants will be evaluated by both the RA and PI at each
      follow-up appointment.

      The HVLT-R will be given at baseline, and weeks 12, 24, 28, 40, and 52; this will be the
      primary outcome measure. Other cognitive assessments will be performed at these same visits
      as well.
    

Intervention name(s): Memantine 10 mg capsule; Memantine-matched Placebo capsule
Intervention type(s): Drug; Drug
Intervention description(s): Memantine oral capsule was initiated at 5 mg/day at Randomization (Week 0), then titrated to 5 mg twice a day at Week 2, then increased to 10 mg in the morning and 5 mg in the evening at Week 3, and then to 10 mg twice a day (intervention dose) at Weeks 4-24. For the participants in the "Placebo, then Memantine" arm, the same titration schedule was maintained after the 4-week washout period (Week 28-52).; Memantine-matched oral Placebo capsule was initiated at Randomization (Week 0) and maintained Weeks 0-24 in a manner consistent with the active drug titration schedule. The number of placebo capsules matched the number of active drug capsules at each titration checkpoint. For the participants in the "Memantine, then Placebo" arm, the same titration schedule was maintained after the 4-week washout period (Week 28-52).
Other intervention name(s): Namenda; Sugar pill
Intervention MeSH terms: Memantine
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: memantine; cognition; corticosteroid; prednisone; memory; hippocampus