Reversing Corticosteroid Induced Memory Impairment

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by University of Texas Southwestern Medical Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Sherwood Brown, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier:
NCT01142310
First received: June 9, 2010
Last updated: May 14, 2014
Last verified: May 2014
  Purpose

Stress and corticosteroid exposure are associated with changes in both the human and animal hippocampus. An extensive literature suggests that corticosteroid-induced changes in the hippocampus are, in part, mediated through increases in extracellular glutamate. In animals, agents that decrease glutamate release prevent dendritic changes in the hippocampus secondary to stress or corticosterone. We have developed a research program using patients receiving prescription corticosteroids (e.g., prednisone) to explore the effects of corticosteroids on the human hippocampus. Our research program is translational in focus, with a goal of exploring whether the reported effects of corticosteroids on the animal hippocampus are also found in humans. A current focus of our research is examining glutamate release inhibitors in patients taking corticosteroids. We have both open-label and placebo-controlled pilot data suggesting that the glutamate release inhibitor lamotrigine is associated with significant improvement in declarative memory (a measure of hippocampal performance) in this population. A definitive study examining declarative memory in corticosteroid-dependent patients receiving lamotrigine vs. placebo is proposed. Neuroimaging and mood will also be assessed.


Condition Intervention Phase
Memory Impairment
Drug: Lamotrigine
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Health Services Research
Official Title: Reversing Corticosteroid Induced Memory Impairment

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Determine if lamotrigine is associated with greater improvement in declarative memory than placebo in patients receiving prescription corticosteroids. [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    The Rey Auditory Verbal Learning Test (RAVLT) will be the cognitive assessment used for primary outcome measure.


Estimated Enrollment: 50
Study Start Date: June 2010
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Lamotrigine
Lamotrigine has a complex mechanism of action that appears to involve the inhibition of voltage-sensitive sodium channels resulting in a stabilization of membranes and inhibition of presynaptic glutamate release. Lamotrigine attenuates cerebral release of glutamate associated with cerebral ischemia in vitro and in vivo. Lamotrigine prevents cognitive and histologic changes in the hippocampus in animal models of ischemia. In patients with seizure disorders, decreases in plasma glutamate levels with lamotrigine are associated with a reduction in seizures
Drug: Lamotrigine
Lamotrigine has a complex mechanism of action that appears to involve the inhibition of voltage-sensitive sodium channels resulting in a stabilization of membranes and inhibition of presynaptic glutamate release. Lamotrigine attenuates cerebral release of glutamate associated with cerebral ischemia in vitro and in vivo. Lamotrigine prevents cognitive and histologic changes in the hippocampus in animal models of ischemia. In patients with seizure disorders, decreases in plasma glutamate levels with lamotrigine are associated with a reduction in seizures. Lamotrigine or identical appearing placebo will be initiated at 25 mg/day and upwardly titrated to a dose of 400 mg/day over 10 weeks.
Placebo Comparator: Placebo Drug: Placebo
Placebo matching active medication in all other physical aspects.

  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 men and women
  • Physician diagnosis of any chronic medical condition requiring treatment with oral corticosteroids confirmed by chart review and/or patients assessment by the PI or co-I.s.
  • Receiving prednisone therapy of at least 5 mg of prednisone daily for at least 6 months with anticipated treatment for ≥ 15 additional months.

Exclusion Criteria:

  • Baseline RAVLT total T-Score ≥ 60
  • Illnesses associated with CNS involvement (e.g., multiple sclerosis, lupus, seizures, brain tumors, head injury with loss of consciousness of more than 30 minutes) or cognitive impairment (e.g., lifetime drug or alcohol dependence, schizophrenia, and mood disorders — e.g., bipolar disorder, major depressive disorder) that appear to be unrelated to corticosteroid use or history of ventilator use that suggests hypoxia. We will include patients with lupus if they do not appear, based on medical history and discussion with treating physician, have significant CNS involvement. We will include participants with brief loss of consciousness. In prior studies we have found that many otherwise eligible participants were excluded due to very brief LOC in childhood or in a motor vehicle accident.
  • Mental retardation or other severe cognitive impairment.
  • Pregnant or nursing women.
  • Severe or life-threatening medical illness that would make completion of study unlikely or study participation potentially unsafe (e.g., highly unstable asthma requiring frequent hospitalization)
  • Contraindications to lamotrigine therapy (severe side effects in the past, taking medications such as some anticonvulsants with drug-drug interactions with lamotrigine).
  • High risk or 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 that includes a plan and intent
  • Therapy with medications (valproate, carbamazepine, primidone, phenytoin, rifampin, phenobarbital) that alter the metabolism of lamotrigine
  • 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: NCT01142310

Contacts
Contact: Nasreen Sayed, MS 214-645-6965 nasreen.sayed@utsouthwestern.edu
Contact: Sherwood Brown, MD, PhD 214-645-6950 Sherwood.Brown@UTSouthwestern.edu

Locations
United States, Texas
Parkland Health and Hospital System (Asthma, Allergy, & Arthritis Clinics) Recruiting
Dallas, Texas, United States, 75235
Contact: David Khan, MD    214-648-3004 ext 83004    David.Khan@utsouthwestern.edu   
Sponsors and Collaborators
University of Texas Southwestern Medical Center
  More Information

No publications provided

Responsible Party: Sherwood Brown, Professor, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier: NCT01142310     History of Changes
Other Study ID Numbers: 122009-028
Study First Received: June 9, 2010
Last Updated: May 14, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Memory Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Lamotrigine
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Voltage-Gated Sodium Channel Blockers
Sodium Channel Blockers

ClinicalTrials.gov processed this record on September 14, 2014