Attenuation of Corticosteroid Induced Hippocampal Changes
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Attenuation of Corticosteroid Induced Hippocampal Changes|
- Hopkins Verbal Learning Test-Revised (HVLT-R) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]The Hopkins Verbal Learning Test-Revised (HVLT-R) consists of 12 nouns read aloud for three consecutive trials with each trial followed by a free-recall trial. Delayed recall and recognition of the wordlist is tested following a 20- to 25-minute delay. Six comparable alternate forms, given in a set order, will be used to minimize practice effects. The proposed study will examine total words learned over 3 trials and delayed recall.
|Study Start Date:||January 2012|
|Estimated Study Completion Date:||June 2017|
|Estimated Primary Completion Date:||December 2016 (Final data collection date for primary outcome measure)|
Active Comparator: Intervention
This arm will be given memantine intervention at the beginning of the trial. Following the washout period, this arm will be switched to placebo.
Memantine is a noncompetitive NMDA receptor antagonist used to help treat Alzheimer's disease.
Other Name: Namenda
Placebo Comparator: Placebo
This group will start off on placebo at the beginning of the study. Following the washout period, this arm will be switched to the memantine intervention.
Inactive ingredient matching the active medication in appearance
Other Name: Sugar-pill
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 compensated and receive bus passes at each appointment, plus a monetary incentive for compliance. 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01656187
|United States, Texas|
|Aston Ambulatory Care Center, Allergy and Immunology|
|Dallas, Texas, United States, 75390-8872|
|Principal Investigator:||Sherwood Brown, PhD, MD||UT Southwestern Medical Center|