Reversing Corticosteroid Induced Memory Impairment
This study is currently recruiting participants.
Verified April 2013 by University of Texas Southwestern Medical Center
Sponsor:
University of Texas Southwestern Medical Center
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: April 10, 2013
Last verified: April 2013
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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: | June 2015 |
| Estimated Primary Completion Date: | December 2013 (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
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: | April 10, 2013 |
| 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 Calcium Channel Blockers |
Membrane Transport Modulators Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Cardiovascular Agents Therapeutic Uses Anticonvulsants Central Nervous System Agents |
ClinicalTrials.gov processed this record on May 19, 2013