Clinical trial NCT01656187: Attenuation of Corticosteroid Induced Hippocampal Changes
Official title: Attenuation of Corticosteroid Induced Hippocampal Changes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Organic Memory Impairment
Keywords: memantine
cognition
corticosteroid
prednisone
memory
hippocampus
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2012-08-02
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of any chronic medical condition requiring treatment with oral corticosteroids confirmed by chart review and/or patient assessment by Dr. Khan (co-I).
* Receiving prednisone therapy of at least 5 mg of prednisone/day for at least 6 months with anticipated treatment for ≥ 12 additional months.
* Age 18-65 years.
* Baseline CVLT-II total T score ≤ 54.

Exclusion Criteria:

* Illnesses associated with CNS involvement (e.g., seizures, brain tumors, head injury with loss of consciousness) or cognitive impairment (e.g., substance dependence within the past 2 years, bipolar disorder) Potential participants with mood symptoms secondary to corticosteroids (based on SCID) will not be excluded because this could selectively exclude subjects who are sensitive to the CNS effects of corticosteroids.
* Vulnerable populations (e.g. severe cognitive impairment, pregnant or nursing women, prisoners).
* Severe or life-threatening medical illness that would make completion of study unlikely
* Contraindications to memantine therapy (e.g. severe side effects in the past)
* Danger to self or others as defined by \> 1 lifetime suicide attempt or assault, any suicide attempt or assault within the past year, and active suicidal or homicidal ideation with plan and intent.
* Metal implants, claustrophobia, or other contraindications to MRI

Primary outcomes:
measure: Hopkins Verbal Learning Test-Revised (HVLT-R) Total Score
timeFrame: Baseline and 24 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Aston Ambulatory Care Center, Allergy and Immunology
state: Texas
Study officials:
affiliation: UT Southwestern Medical Center
name: Sherwood Brown, PhD, MD
role: PRINCIPAL_INVESTIGATOR
References: