Clinical trial NCT01656187
Conditions: Organic Memory Impairment
Keywords: memantine cognition corticosteroid prednisone memory hippocampus
Sponsor: University of Texas Southwestern Medical Center
Start date: 2012-01-01; Completion date: 2017-01-01
Enrollment: 46 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief 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.

Arms: arm 1: Participants first received Memantine 10 mg capsule twice a day for 24 weeks. After a washout period of 4 weeks, they then received Placebo capsule (matching Memantine 10 mg capsule) twice a day for 24 weeks. arm 2: Participants first received Placebo capsule (matching Memantine 10 mg capsule) twice a day for 24 weeks. After a washout period of 4 weeks, they then received Memantine 10 mg capsule twice a day for 24 weeks.
Interventions: intervention 1: Memantine 10 mg capsule intervention 2: Memantine-matched Placebo capsule
Intervention descriptions: intervention 1: 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). intervention 2: 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).

Protocol documents: