Memory ImpairmentPhase 4NCT01142310
Reversing Corticosteroid Induced Memory Impairment
A Phase 4 study testing Lamotrigine in people with Memory Impairment, run by University of Texas Southwestern Medical Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Memory Impairment
- What is being tested?
- Lamotrigine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 54 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2010to Jun 2015
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
Show all 9Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Parkland Health and Hospital System (Asthma, Allergy, & Arthritis Clinics)
Dallas, Texas, 75235
About this study
Medically stable outpatients receiving chronic oral corticosteroid therapy were enrolled in a 48-week randomized, double-blind, placebo-controlled, parallel-group, trial of lamotrigine.
Read the 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.
- Conditions
- Memory Impairment
- Being tested
- Lamotrigine, Placebo
- Medical subject headings
- Memory Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LamotrigineDrug
Also called Lamictal
Lamotrigine will be initiated at 25 mg/day and upwardly titrated to a dose of 400 mg/day over 10 weeks.
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Lamotrigine | Active comparator | 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. Receives: Drug: Lamotrigine |
| Placebo | Placebo comparator | Placebo administered the same as the Lamotrigine just described. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2010 (estimated)
- Study startJun 2010
- Primary completionJun 2015
- Study completionJun 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Memory ImpairmentStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Texas Southwestern Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Sherwood Brown, University of Texas Southwestern Medical Center
- Investigators
- E. Sherwood Brown, M.D., Ph.D., Principal investigator, University of Texas Southwestern Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01142310
- Sponsor's protocol ID
- 122009-028
- Other IDs
- R01MH082845
- Status last verified
- Jul 2018
- First submitted
- 9 Jun 2010
- Last updated
- 27 Aug 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 27 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Reversing Corticosteroid Induced Memory Impairment
- ClinicalTrials.gov ID
- NCT01142310
- Acronym / sponsor ID
- 122009-028
- Conditions
- Memory Impairment
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 54 participants (actual)
- Lead sponsor
- University of Texas Southwestern Medical CenterUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- Jun 2010
- Primary completion
- Jun 2015 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 11 Jun 2010 (estimated)
- Results
- Posted 27 Aug 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Lamotrigine | Active comparator | Drug: LamotrigineDose 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 | Placebo comparator | Drug: PlaceboPlacebo administered the same as the Lamotrigine just described. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (9 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LamotrigineAlso: LamictalLamotrigine will be initiated at 25 mg/day and upwardly titrated to a dose of 400 mg/day over 10 weeks. | Drug | Lamotrigine |
| Placebo | Drug | Placebo |
Primary outcome
The Rey Auditory Verbal Learning Test (RAVLT)
Time frame: 48 weeks
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Aug 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
E. Sherwood Brown, M.D., Ph.D. principal investigator
University of Texas Southwestern Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Lamotrigine in people with Memory Impairment, run by University of Texas Southwestern Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Aug 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Rey Auditory Verbal Learning Test (RAVLT) (time frame: 48 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Aug 2018; AzTrials last refreshed its copy on 28 Oct 2026.