Back to resultsReversing Corticosteroid Induced Memory Impairment
Primary Purpose
Memory Impairment
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Lamotrigine
Placebo
Sponsored by
About this trial
This is an interventional health services research trial for Memory Impairment
Eligibility 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
Sites / Locations
- Parkland Health and Hospital System (Asthma, Allergy, & Arthritis Clinics)
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Lamotrigine
Placebo
Arm Description
Dose titration: begin at Baseline at 25mg PO QD for two weeks. Increase to 50mg PO QD at Week 2 for two weeks. Increase to 100mg PO QD at Week 4. Increase to 150mg PO QD at Week 5. Increase to 200mg PO QD at Week 6. Increase to 250mg PO QD at Week 7. Increase to 300mg PO QD at Week 8. Increase to 350mg PO QD at Week 9. Increase to 400mg PO QD at Week 10. Stay at 400mg PO QD from Week 10 to Week 48.
Placebo administered the same as the Lamotrigine just described.
Outcomes
Primary Outcome Measures
The Rey Auditory Verbal Learning Test (RAVLT)
The Rey Auditory Verbal Learning Test (RAVLT) measures verbal or declarative learning and memory. The test consists of 15 nouns read aloud for five consecutive trials with each trial followed by a free-recall trial. Following the fifth trial, an interference list of 15 different words is presented followed by a free-recall trial of that list. Delayed recall of the first list is tested immediately following the interference list and after a 20-minute delay. A recognition test of 50 words including the 15 original words is presented after the delayed recall. Equivalent, alternative versions (different words) were used to minimize practice or learning effects from repeated administration. The raw scores (number of words correct across trials 1-5) are converted to standardized T-scores (M=50; SD=10). This score is used to determine the participant's performance in relation to norm-referenced expectations based on age and sex. A higher score reflects better performance.
Secondary Outcome Measures
Full Information
NCT ID
NCT01142310
First Posted
June 9, 2010
Last Updated
July 27, 2018
Sponsor
University of Texas Southwestern Medical Center
Collaborators
National Institute of Mental Health (NIMH)
1. Study Identification
Unique Protocol Identification Number
NCT01142310
Brief Title
Reversing Corticosteroid Induced Memory Impairment
Official Title
Reversing Corticosteroid Induced Memory Impairment
Study Type
Interventional
2. Study Status
Record Verification Date
July 2018
Overall Recruitment Status
Completed
Study Start Date
June 2010 (undefined)
Primary Completion Date
June 2015 (Actual)
Study Completion Date
June 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Texas Southwestern Medical Center
Collaborators
National Institute of Mental Health (NIMH)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Medically stable outpatients receiving chronic oral corticosteroid therapy were enrolled in a 48-week randomized, double-blind, placebo-controlled, parallel-group, trial of lamotrigine.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Memory Impairment
7. Study Design
Primary Purpose
Health Services Research
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
54 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Lamotrigine
Arm Type
Active Comparator
Arm Description
Dose titration: begin at Baseline at 25mg PO QD for two weeks. Increase to 50mg PO QD at Week 2 for two weeks. Increase to 100mg PO QD at Week 4. Increase to 150mg PO QD at Week 5. Increase to 200mg PO QD at Week 6. Increase to 250mg PO QD at Week 7. Increase to 300mg PO QD at Week 8. Increase to 350mg PO QD at Week 9. Increase to 400mg PO QD at Week 10. Stay at 400mg PO QD from Week 10 to Week 48.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo administered the same as the Lamotrigine just described.
Intervention Type
Drug
Intervention Name(s)
Lamotrigine
Other Intervention Name(s)
Lamictal
Intervention Description
Lamotrigine will be initiated at 25 mg/day and upwardly titrated to a dose of 400 mg/day over 10 weeks.
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
The Rey Auditory Verbal Learning Test (RAVLT)
Description
The Rey Auditory Verbal Learning Test (RAVLT) measures verbal or declarative learning and memory. The test consists of 15 nouns read aloud for five consecutive trials with each trial followed by a free-recall trial. Following the fifth trial, an interference list of 15 different words is presented followed by a free-recall trial of that list. Delayed recall of the first list is tested immediately following the interference list and after a 20-minute delay. A recognition test of 50 words including the 15 original words is presented after the delayed recall. Equivalent, alternative versions (different words) were used to minimize practice or learning effects from repeated administration. The raw scores (number of words correct across trials 1-5) are converted to standardized T-scores (M=50; SD=10). This score is used to determine the participant's performance in relation to norm-referenced expectations based on age and sex. A higher score reflects better performance.
Time Frame
48 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
E. Sherwood Brown, M.D., Ph.D.
Organizational Affiliation
UT Southwestern Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Parkland Health and Hospital System (Asthma, Allergy, & Arthritis Clinics)
City
Dallas
State/Province
Texas
ZIP/Postal Code
75235
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Reversing Corticosteroid Induced Memory Impairment
We'll reach out to this number within 24 hrs