Attenuation of Corticosteroid Induced Hippocampal Changes

Study ID
032011-007

Cancer Related
No

Healthy Volunteers
No

Study Sites

  • UT Southwestern-Other
  • Clements University Hospital
  • UT Southwestern-Clinical Translational Research Center (CTRC)
  • UT Southwestern Ambulatory Services
  • Parkland Health & Hospital System

Contact
Kendra Malone
469/569-0168
kendra.malone@utsouthwestern.edu

Principal Investigator
Edson Brown

Official Title

Attenuation of Corticosteroid Induced Hippocampal Changes

Brief Overview


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.

Summary


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.

Participant Eligibility


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