EpilepsyPhase 4NCT01318408
Levetiracetam: The Anti-Convulsant of Choice for Elderly Patients With Dementia
A Phase 4 study testing Levetiracetam in people with Epilepsy, run by Drexel University College of Medicine at 1 site in United States.
Trial summary
Elderly persons with dementia are at risk for seizures, however, traditional anticonvulsants are poorly tolerated in this population. Our goal is to examine Levetiracetam (Keppra) in elderly dementia patients with seizures. Read more about this study
- Who is it for?
- Ages 60 to 90 years
- Conditions the study is for
- Epilepsy
- What is being tested?
- Levetiracetam
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2006to Mar 2008
- 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 60 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Able to give written informed consent
- Meet validated clinical criteria for Alzheimer's disease, mixed dementia or MCI
- Age range greater than or equal to 60 years
- Stable general medical condition as assessed by the investigator
- Seizures which are partial in onset (with or without secondary generalization)
- Subjects with 4 or fewer seizures per month
- MMSE score of less than 28 at baseline
- Patients who are currently being treated with anticonvulsants or those with new onset seizures.
Who cannot join
- Patients with other clinically significant organic or neurological diseases. Patients considered medically unstable
- Patients in end stage renal disease requiring hemodialysis
- Patients with a known hypersensitivity to Levetiracetam
- Patients with primary generalized epilepsy
- Patients with brain tumors or other significant CNS abnormalities that are the primary cause of the seizures
- Patients with a history of status epilepticus
- Patients with severe psychiatric diagnoses or severe behavioral problems
- Dementia patients lacking a caregiver.
Trial locations and contacts
1 site in 1 country.
United States1 site
Drexel University College of Medicine, Dept of Neurology
Philadelphia, Pennsylvania, 19102
About this study
Official title: A Prospective, Phase 4, Open-Label, Twelve-Week Study to Examine the Cognitive Impact and Tolerability of Levetiracetam (Keppra) in Elderly Patients With Seizures of Partial Onset
Elderly persons with dementia are at risk for seizures, however, traditional anticonvulsants are poorly tolerated in this population. Our goal is to examine Levetiracetam (Keppra) in elderly dementia patients with seizures. While it has been established that Keppra controls seizures in this age group, it is important to demonstrate that treatment with Keppra would not affect cognitive abilities in this large population of patients . As this population is already cognitively impaired, the best choice of anticonvulsant would be one that does not further compromise their cognitive abilities. Keppra is an excellent anticonvulsant agent in the elderly for a variety of reasons, including safety, favorable side effect profile, lack of interaction with other drugs, and efficacy. Our retrospective pilot data suggests that cognition is not negatively affected by Keppra. The current prospective study will assess the cognitive abilities of persons with cognitive impairment at baseline and at weeks 4 and 12. The overall objective is to determine the cognitive tolerability of Keppra for seizures in elderly cognitively impaired patients.
Read the detailed description
This is a prospective, phase 4, open label, twelve week study. The study will consist of a 4 week titration phase followed by an 8 week assessment phase. All clinic visits will be conducted at Drexel University College of Medicine Department of Neurology at 219 N. Broad St., Phila., PA.
Visit one will include reviewing and signing the written informed consent form, obtaining relevant demographic data, and then routine blood work. The baseline frequency, duration and type of seizures our subjects experience will be documented, as will their current antiepileptic medications. Baseline history and a physical and neurological examination will be performed, including vital signs. Testing will include baseline measurements of cognition, function (activities of daily living), and behavior. Cognitive testing will include Folstein's Minimental State examination (MMSE), and the ADAS-cog. Our overall assessment will include the Modified Schwab and England Activities of Daily Living Scale. Behavioral assessment will include Tariot's Behavior Ratings Scale and the Cohen-Mansfield Agitation Inventory (CMAI; long form). Levetiracetam will be initiated and instructions for follow up will be given. Because the goal is cognitive tolerability, Levetiracetam will be used as either an add-on agent or as primary monotherapy.
During week two, a follow up telephone assessment will be done to review the instructions and to determine whether any medical changes or adverse events occurred. Adverse events will be assessed by direct questioning and spontaneous patient/caregiver reports. The date, number, duration and type of seizures any of our subjects experience will also be documented.
At the third assessment (week 4), a follow up physical and neurological examination will be done, including vital signs, and the mental testing, including the tests of cognition, function and behavior will be repeated. An assessment will be made to determine whether adverse events occurred. Adverse events will be assessed by review of the subject's seizure log, physician observation, direct questioning and spontaneous reports. The date, number, duration and type of seizures any subject experiences will also be documented. In cases where levetiracetam is an add-on agent, we will attempt to taper the preceding medications if seizure control has been demonstrated. Cognitive testing will be done when subjects are not in a post-ictal state. Any subject who has had a seizure with generalization within 24 hours of their scheduled testing will be rescheduled to another day within one week.
At week twelve, a full follow up mental status assessment will be done for the final assessment. Testing will be the same as that done at weeks 1 (baseline) and 4. Again, cognitive testing will not be done when subjects are in a post-ictal state. Any subject who has had a seizure with generalization within 24 hours of their scheduled testing will be rescheduled to the next available day, within one week.
Follow up blood work and a screen for adverse events will also be obtained at that time. Again, adverse events will be assessed by review of their seizure log, physician observation, direct questioning and spontaneous reports. The date, number, duration and type of seizures will be documented.
- Conditions
- Epilepsy
- Being tested
- Levetiracetam
- Medical subject headings
- Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LevetiracetamDrug
Also called Levetiracetam is the brand name for Keppra
Titration of Keppra will start at 250 mg by mouth twice daily for three days. Then 500 mg by mouth twice daily for three days. Then 750 mg by mouth twice daily for the duration of the study, or for as long as treatment is necessary. This titration schedule is subject to change based on subject's tolerability.
| Study group | Role | What they receive |
|---|---|---|
| Levetiracetam | Experimental | Levetiracetam was titrated over 4 weeks, with initial dosing of 250 mg bis in die (BID). Dosing was flexible and was based on the prescribing physician's discretion. Receives: Drug: Levetiracetam |
What is being measured
The primary outcome is the main question the study is designed to answer.
MMSE at Baseline and at Three (3) Months.
The MMSE (Folstein et al 1975) is a brief cognitive test assessing general cognitive function that has been employed in numerous clinical trials of Food and Drug Administration (FDA) products approved for the treatment of AD. The MMSE consists of five components; 1) orientation to time and place, 2) registration of three words, 3) attention and calculation, 4) recall of three words, and 5) language. The scores from each of the five components are summed to obtain the overall MMSE score. The score can range from 0 to 30, with lower scores indicating greater impairment in function.
Measured: Baseline and Three months
ADAS-cog at Baseline and at 3 Months.
ADAScog (Alzheimer's Disease Assessment Scale-cognitive subscale) consists of 11 tasks measuring the disturbances of memory, language, praxis, attention and other cognitive abilities which are often referred to as the core symptoms of AD. Score ranges from 0 - 70.
Lower scores (negative change) indicate improvements on the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-cog).
Measured: Baseline and Three (3) months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2011 (estimated)
- Study startNov 2006
- Primary completionMar 2008
- Study completionMar 2008
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for EpilepsyStudies 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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Drexel University College of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- UCB Pharma
- Responsible party
- Sponsor
- Investigators
- Carol Lippa, MD, Principal investigator, Drexel University College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01318408
- Sponsor's protocol ID
- KEPPRA
- Other IDs
- WIRB # 20061543
- Status last verified
- Sep 2018
- First submitted
- 16 Mar 2011
- Last updated
- 12 Oct 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Ritchie K, Touchon J. Mild cognitive impairment: conceptual basis and current nosological status. Lancet. 2000 Jan 15;355(9199):225-8. doi: 10.1016/S0140-6736(99)06155-3. No abstract available.
PubMed 10675135
Study at a glance
From the registry record, last updated by the sponsor on 12 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Phase 4, Open-Label, Twelve-Week Study to Examine the Cognitive Impact and Tolerability of Levetiracetam (Keppra) in Elderly Patients With Seizures of Partial Onset
- ClinicalTrials.gov ID
- NCT01318408
- Acronym / sponsor ID
- KEPPRA
- Conditions
- Epilepsy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Drexel University College of MedicineUniversity, hospital or other
- Collaborators
- UCB Pharma
- Study start
- Nov 2006
- Primary completion
- Mar 2008 (actual)
- Study completion
- Mar 2008 (actual)
- First posted
- 18 Mar 2011 (estimated)
- Results
- Posted 23 Jun 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Elderly persons with dementia are at risk for seizures, however, traditional anticonvulsants are poorly tolerated in this population. Our goal is to examine Levetiracetam (Keppra) in elderly dementia patients with seizures. While it has been established that Keppra controls seizures in this age group, it is important to demonstrate that treatment with Keppra would not affect cognitive abilities in this large population of patients . As this population is already cognitively impaired, the best choice of anticonvulsant would be one that does not further compromise their cognitive abilities. Keppra is an excellent anticonvulsant agent in the elderly for a variety of reasons, including safety, favorable side effect profile, lack of interaction with other drugs, and efficacy. Our retrospective pilot data suggests that cognition is not negatively affected by Keppra. The current prospective study will assess the cognitive abilities of persons with cognitive impairment at baseline and at weeks 4 and 12. The overall objective is to determine the cognitive tolerability of Keppra for seizures in elderly cognitively impaired patients.
Detailed description
This is a prospective, phase 4, open label, twelve week study. The study will consist of a 4 week titration phase followed by an 8 week assessment phase. All clinic visits will be conducted at Drexel University College of Medicine Department of Neurology at 219 N. Broad St., Phila., PA.
Visit one will include reviewing and signing the written informed consent form, obtaining relevant demographic data, and then routine blood work. The baseline frequency, duration and type of seizures our subjects experience will be documented, as will their current antiepileptic medications. Baseline history and a physical and neurological examination will be performed, including vital signs. Testing will include baseline measurements of cognition, function (activities of daily living), and behavior. Cognitive testing will include Folstein's Minimental State examination (MMSE), and the ADAS-cog. Our overall assessment will include the Modified Schwab and England Activities of Daily Living Scale. Behavioral assessment will include Tariot's Behavior Ratings Scale and the Cohen-Mansfield Agitation Inventory (CMAI; long form). Levetiracetam will be initiated and instructions for follow up will be given. Because the goal is cognitive tolerability, Levetiracetam will be used as either an add-on agent or as primary monotherapy.
During week two, a follow up telephone assessment will be done to review the instructions and to determine whether any medical changes or adverse events occurred. Adverse events will be assessed by direct questioning and spontaneous patient/caregiver reports. The date, number, duration and type of seizures any of our subjects experience will also be documented.
At the third assessment (week 4), a follow up physical and neurological examination will be done, including vital signs, and the mental testing, including the tests of cognition, function and behavior will be repeated. An assessment will be made to determine whether adverse events occurred. Adverse events will be assessed by review of the subject's seizure log, physician observation, direct questioning and spontaneous reports. The date, number, duration and type of seizures any subject experiences will also be documented. In cases where levetiracetam is an add-on agent, we will attempt to taper the preceding medications if seizure control has been demonstrated. Cognitive testing will be done when subjects are not in a post-ictal state. Any subject who has had a seizure with generalization within 24 hours of their scheduled testing will be rescheduled to another day within one week.
At week twelve, a full follow up mental status assessment will be done for the final assessment. Testing will be the same as that done at weeks 1 (baseline) and 4. Again, cognitive testing will not be done when subjects are in a post-ictal state. Any subject who has had a seizure with generalization within 24 hours of their scheduled testing will be rescheduled to the next available day, within one week.
Follow up blood work and a screen for adverse events will also be obtained at that time. Again, adverse events will be assessed by review of their seizure log, physician observation, direct questioning and spontaneous reports. The date, number, duration and type of seizures will be documented.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Levetiracetam | Experimental | Drug: LevetiracetamLevetiracetam was titrated over 4 weeks, with initial dosing of 250 mg bis in die (BID). Dosing was flexible and was based on the prescribing physician's discretion. |
Who may qualify
- Ages
- 60 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Able to give written informed consent
- Meet validated clinical criteria for Alzheimer's disease, mixed dementia or MCI
- Age range greater than or equal to 60 years
- Stable general medical condition as assessed by the investigator
- Seizures which are partial in onset (with or without secondary generalization)
Key exclusion criteria (8 listed)
- Patients with other clinically significant organic or neurological diseases. Patients considered medically unstable
- Patients in end stage renal disease requiring hemodialysis
- Patients with a known hypersensitivity to Levetiracetam
- Patients with primary generalized epilepsy
- Patients with brain tumors or other significant CNS abnormalities that are the primary cause of the seizures
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 |
|---|---|---|
| LevetiracetamAlso: Levetiracetam is the brand name for KeppraTitration of Keppra will start at 250 mg by mouth twice daily for three days. Then 500 mg by mouth twice daily for three days. Then 750 mg by mouth twice daily for the duration of the study, or for as long as treatment is necessary. This titration schedule is subject to change based on subject's tolerability. | Drug | Levetiracetam |
Primary outcome
MMSE at Baseline and at Three (3) Months.
Time frame: Baseline and Three months
The MMSE (Folstein et al 1975) is a brief cognitive test assessing general cognitive function that has been employed in numerous clinical trials of Food and Drug Administration (FDA) products approved for the treatment of AD. The MMSE consists of five components; 1) orientation to time and place, 2) registration of three words, 3) attention and calculation, 4) recall of three words, and 5) language. The scores from each of the five components are summed to obtain the overall MMSE score. The score can range from 0 to 30, with lower scores indicating greater impairment in function.
ADAS-cog at Baseline and at 3 Months.
Time frame: Baseline and Three (3) months
ADAScog (Alzheimer's Disease Assessment Scale-cognitive subscale) consists of 11 tasks measuring the disturbances of memory, language, praxis, attention and other cognitive abilities which are often referred to as the core symptoms of AD. Score ranges from 0 - 70. Lower scores (negative change) indicate improvements on the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-cog).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Oct 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 10675135Ritchie K, Touchon J. Mild cognitive impairment: conceptual basis and current nosological status. Lancet. 2000 Jan 15;355(9199):225-8. doi: 10.1016/S0140-6736(99)06155-3. No abstract available.
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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.
Carol Lippa, MD principal investigator
Drexel University College of Medicine
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 Levetiracetam in people with Epilepsy, run by Drexel University College of Medicine 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 8 inclusion and 8 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 12 Oct 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. 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 23 Jun 2015). 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?
MMSE at Baseline and at Three (3) Months. (time frame: Baseline and Three months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01318408, which also lists 1 linked publication.
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 12 Oct 2018.