Attenuation of Corticosteroid Induced Hippocampal Changes

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by University of Texas Southwestern Medical Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier:
NCT01656187
First received: July 31, 2012
Last updated: April 30, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Organic Memory Impairment
Drug: Memantine
Drug: Placebo
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
Official Title: Attenuation of Corticosteroid Induced Hippocampal Changes

Resource links provided by NLM:


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

Primary Outcome Measures:
  • 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.


Estimated Enrollment: 50
Study Start Date: January 2012
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: Memantine
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.
Drug: Placebo
Inactive ingredient matching the active medication in appearance
Other Name: Sugar-pill

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 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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT01656187

Contacts
Contact: Alexander J Lo, MPH 214-645-6967 alexander.lo@utsouthwestern.edu
Contact: Sherwood Brown, MD, PhD 214-645-6948 sherwood.brown@utsouthwestern.edu

Locations
United States, Texas
Aston Ambulatory Care Center, Allergy and Immunology Recruiting
Dallas, Texas, United States, 75390-8872
Contact: David Khan, MD    214-645-2866    dave.khan@utsouthwestern.edu   
Sponsors and Collaborators
University of Texas Southwestern Medical Center
Investigators
Principal Investigator: Sherwood Brown, PhD, MD UT Southwestern Medical Center
  More Information

No publications provided

Responsible Party: University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier: NCT01656187     History of Changes
Other Study ID Numbers: 032011-007, 1R01DA029596
Study First Received: July 31, 2012
Last Updated: April 30, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Texas Southwestern Medical Center:
memantine
cognition
corticosteroid
prednisone
memory
hippocampus

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

ClinicalTrials.gov processed this record on September 18, 2014