Memantine or Riluzole Prophylaxis for Corticosteroid-induced Mood and Declarative Memory Changes

This study has been terminated.
(Study finished enrollment but data was never sent for publishing.)
Sponsor:
Information provided by (Responsible Party):
Sherwood Brown, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier:
NCT00283309
First received: January 24, 2006
Last updated: April 19, 2013
Last verified: April 2013
  Purpose

The primary purpose is to determine if patients scheduled to receive prescription corticosteroid therapy for inflammatory illnesses who are given either memantine or riluzole pretreatment will show lesser declarative memory impairment than those receiving placebo.

The exploratory purpose is to determine if patients scheduled to receive prescription corticosteroid therapy for inflammatory illnesses who are given memantine or riluzole pretreatment will show a smaller increase in manic/hypomanic symptom severity than those receiving placebo.


Condition Intervention Phase
Mood
Memory Deficit
Drug: Memantine
Drug: Riluzole
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

Resource links provided by NLM:


Further study details as provided by University of Texas Southwestern Medical Center:

Enrollment: 20
Study Start Date: November 2005
Study Completion Date: April 2007
Primary Completion Date: April 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Memantine
Memantine is used to determine if patients given pretreatment to corticosteroid therapy for inflammatory illnesses will show lesser declarative memory impairment than those receiving placebo. Baseline 10mg x 3 days, then 10mg BID x 4 days.
Drug: Memantine
Placebo Comparator: Placebo
Inactive ingredient matching the active medication in appearance
Drug: Memantine Drug: Riluzole
Active Comparator: Riluzole
Riluzole is given to patients receiving corticosteroid therapy for inflammatory illnesses pretreatment to determine if they show lesser declarative memory impairment than those receiving placebo. Baseline 50mg x 3 days, then 50mg BID x 4 days.
Drug: Riluzole

Detailed Description:

Twenty five (25) outpatients with pulmonary (e.g. asthma, cystic fibrosis) or rheumatic (e.g. rheumatoid arthritis, dermatomyositis) illnesses scheduled to receive a brief course ("burst") of prednisone will be enrolled. The subjects will be randomized to receive memantine, riluzole or placebo beginning immediately prior to the corticosteroid therapy and continuing for one week. Measures of cognition and mood will be compared between the two groups at baseline, day 3, and day 7.

Demographic information including age, gender, frequency and duration of prior corticosteroid therapy and current anticipated dose and duration will be collected at baseline. Baseline measures of mood will be assessed with the Activation subscale of the Internal State Scale (ISS) (primary measure), Hamilton Depression Rating Scale (17-item version), and Young Mania Rating Scale (YMRS). Cognition will be assessed with the RAVLT (primary measure), Stroop, and Digit Span Backwards. The subjects will be given memantine (10 mg), riluzole (50 mg), or identical appearing placebo 1 tablet daily for 3 days and then at the first follow up appointment (day 3) the dose will be increased to BID if no side effects are reported. The subjects will be reassessed twice, at day 3 and day 7. Mood and cognitive measures will be repeated. The study visits will last approximately an hour and a half. Participants will discontinue memantine when they discontinue prednisone. The RA administering assessments will be blinded at all times. Alternative but equivalent versions of the RAVLT and Digit Span Backwards will be given to minimize practice or learning effects. Current and cumulative corticosteroid dose (mg each day X number of days) will be determined and recorded.

HVLT-R test total words recalled scores will be compared between baseline and exit of the active medication phase and placebo phase using a within subjects design and paired t-tests. Based on our prior experience working with corticosteroid-dependent patients we have found them to be very compliant with clinical treatment. Thus, we do not anticipate large numbers of dropouts or missing data. In the case of missing data we will use the last observation carried forward. In our lamotrigine study in a similar population, we found a change in total words recalled on a word list and on the Stroop. Assuming a similar change with memantine, using double-sided, paired t-tests, we could detect a difference with a change in the placebo group with participants on the HVLT-R and up to with participants on the Stroop. Thus, although this is primarily a pilot study to obtain effect sizes for future, larger trials funded by NIH, it should have power to detect clinically meaningful differences between medication and placebo.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 18-70 years old
  • English speaking
  • Able to provide informed consent
  • Scheduled to receive a corticosteroid burst of at least 20 mg prednisone or equivalent for at least 7 days

Exclusion Criteria:

  • History of allergic reaction to memantine and/or riluzole
  • Pregnant or nursing women
  • History of liver disease, myocardial infarction, renal failure, diabetes with poor glycemic control, or other unstable medical condition
  • Mental retardation, dementia, or other severe cognitive disorder
  • Prior prednisone therapy in the last 14 days
  • Current alcohol/substance abuse/dependence
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00283309

Locations
United States, Texas
UT Southwestern
Dallas, Texas, United States, 75390
Sponsors and Collaborators
University of Texas Southwestern Medical Center
Investigators
Principal Investigator: Sherwood Brown The University of Texas Southwestern Medical Center at Dallas
  More Information

Additional Information:
No publications provided

Responsible Party: Sherwood Brown, Principal Investigator, MD/PhD, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier: NCT00283309     History of Changes
Other Study ID Numbers: 042005-018
Study First Received: January 24, 2006
Last Updated: April 19, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Texas Southwestern Medical Center:
Corticosteroids
Riluzole
Memantine
Memory

Additional relevant MeSH terms:
Memantine
Riluzole
Anti-Dyskinesia Agents
Anticonvulsants
Antiparkinson Agents
Central Nervous System Agents
Dopamine Agents
Excitatory Amino Acid Agents
Excitatory Amino Acid Antagonists
Molecular Mechanisms of Pharmacological Action
Neuroprotective Agents
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014