Does Gabapentin and Lamotriginel Have Significantly Fewer Side-Effects While Providing Equal or Better Seizure Control Than the Current Drug Choice, Carbamazepine, for the Treatment of Seizures in the Elderly.
Information source: Department of Veterans Affairs
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Seizures
Intervention: Carbamazepine (Drug); Gabapentin (Drug); Lamotrigine (Drug)
Phase: Phase 3
Status: Completed
Sponsored by: Department of Veterans Affairs
Summary
New onset epilepsy in the elderly occurs in 45,000-50,000 elderly patients each year. These
patients are especially vulnerable to side effects from medications because of changes
caused by the aging process and the fact that these patients often have many common diseases
for which they are already receiving medications for so that the likelihood of drug
interactions is increased. Two new drugs, gabapentin and lamotrigine, have recently been
approved by the FDA as antiepileptic drugs. These drugs have demonstrated efficacy in the
treatment of partial onset seizures, the most common seizures in the elderly. These new
compounds also have favorable side effect profiles and infrequent drug-drug interactions
and, therefore, would be expected to be well-tolerated in the elderly.
Clinical Details
Official title: CSP #428 - Treatment of Seizures in the Elderly Population
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind
Detailed description:
Primary Hypothesis: The primary hypothesis for this study is that one or both of two newly
FDA approved antiepileptic drugs, gabapentin and lamotrigine, will have significantly fewer
side-effects while providing equal or possibly better seizure control than the current
world-wide drug of choice, carbamazepine, for the treatment of seizures in the elderly.
Secondary Hypotheses: Secondary aims of the study are to determine which of the three drugs
being studied (1) has the fewest side-effects, (2) produces the best seizure control, (3)
has the least impairment of cognitive function, (4) has the best effect on mood and (5) has
the best effect on quality of life.
Intervention: Patients are randomized to carbamazepine, gabapentin or lamotrigine. Target
doses are 600mg for carbamazepine (200mg tablets overencapsulated), 1500mg for gabapentin
(300mg capsules), and 150mg for lamotrigine (25mg tablets). Carbamazepine and gabapentin
patients also receive a placebo tablet while lamotrigine patients also receive a placebo
capsule.
Primary Outcomes: The primary outcome measure is retention in the study at 12 months. Major
secondary outcomes are seizure frequency during first 12 months, time to first seizure,
total scores from Systemic Toxicity and Neurotoxicity Rating Scales, the Mattis Dementia
Rating Scale (cognitive function), Hamilton Depression Scale (mood) and SF-36 Health Survey
(quality of life).
Study Abstract: New onset epilepsy in the elderly occurs in 45,000-50,000 elderly patients
each year. These patients are especially vulnerable to side effects from medications
because of changes caused by the aging process and the fact that these patients often have
many common diseases for which they are already receiving medications for so that the
likelihood of drug interactions is increased. Two new drugs, gabapentin and lamotrigine,
have recently been approved by the FDA as antiepileptic drugs. These drugs have
demonstrated efficacy in the treatment of partial onset seizures, the most common seizures
in the elderly. These new compounds also have favorable side effect profiles and infrequent
drug-drug interactions and, therefore, would be expected to be well-tolerated in the
elderly. Thus, the primary objective of this study is to evaluate the tolerability and
efficacy of these two new antiepileptic drugs individually compared to a standard
antiepileptic drug, carbamazepine, in an elderly population (>60 years of age) with new
onset, unprovoked epileptic seizures.
The study is a 63-month, randomized, double-blind trial of three antiepileptic drugs:
carbamazepine, gabapentin, and lamotrigine. Patient recruitment occured during the first 51
months with each patient being followed for at least one year. There were 593 patients
enrolled from 18 VA medical centers. Patients are veterans 60 years of age or older who
have new onset, unprovoked seizures of focal onset, with or without secondary
generalization. Patients with seizures secondary to toxic-metabolic causes, acute medical
or neurological conditions or progressive diseases of the brain such as brain tumors are
excluded. A double-dummy design is being employed to preserve the blind. Target doses for
the study medications are: carbamazepine-600 mg., gabapentin-1500 mg., and lamotrigine-150
mg. Patients are assessed biweekly during the first 8 weeks, every 4 weeks until week 24
and every 8 weeks until week 52. Patients wishing to continue on their study drug after 52
weeks are seen quarterly for an additional year.
RESULTS: For the primary outcome measure of retention at 12 months, there was a
statistically significant (p=0. 0002) overall difference between the treatment groups
(lamotrigine=55. 8%, gabapentin=49. 0%, and carbamazepine=35. 5%). The paired comparisons
indicated significant differences between lamotrigine and carbamazepine (p<0. 0001) and
gabapentin and carbamazepine (p=0. 008). Consideration of reasons for early terminations
indicates significant overall differences (p=0. 001) between treatment groups for early
terminations due to adverse events (lamotrigine=12. 1%, gabapentin=21. 6%, and
carbamazepine=31. 0%. There were significant paired comparisons for lamotrigine vs
carbamazepine (p<0. 0001) and lamotrigine vs gabapentin (p=0. 015). There were no differences
between the treatment groups for percent of patients seizure free at 3, 6, and 12 months or
for the time to first, second, fifth, or tenth seizure (all p>0. 05). When individual
adverse events during the first 12 months on study drug were considered, it was seen that
more gabapentin patients had significantly more weight gain, severe weight gain (>18
pounds), and water retention than patients on either lamotrigine or carbamazepine.
Hypersensitivity (rash of any degree) occurred more frequently with carbamazpine than with
lamotrigine (p=0. 007). The overall conclusion is that lamotrigine and gabapentin should be
considered as initial therapy for older patients with newly diagnosed seizures.
Rowan, A. J., Ramsay, R. E., Collins, J. F., Pryor, F., Boardman, K. D., Uthman, B. M., Spitz,
M., Frederick, T., Towne, A., Carter, G. S., Marks, W., Felicetta, J., Tomyanovich, M. L., and
the VA Cooperative Study 428 Group - New onset geriatric epilepsy. A randomized study of
gabapentin, lamotrigine, and carbamazepine. Neurology 64 1868-1873, 2005
Eligibility
Minimum age: 60 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Veterans 60 years of age or older who have new onset, unprovoked seizures of focal onset,
with or without secondary generalization.
Locations and Contacts
Birmingham VA Medical Center, Birmingham, Alabama 35233, United States
Carl T. Hayden VA Medical Center, Phoenix, Arizona 85012, United States
Vamc - West Los Angeles, Los Angeles, Ca, Los Angeles, California 90073, United States
Vamc - San Diego, San Diego, Ca, San Diego, California 92161, United States
San Francisco VAMC, San Francisco, California 94121, United States
Denver VA Medical Center, Denver, Colorado 80220, United States
Vamc - Bay Pines, Fl, Bay Pines, Florida 33744, United States
Gainesville VA Medical Center, Gainesville, Florida 32608-1197, United States
Miami VA Medical Center, Miami, Florida 33125, United States
Study Chairperson, Miami, Florida 33125, United States
Chicago VA Medical Center (West Side), Chicago, Illinois 60612, United States
Edward Hines Jr. VA Hospital, Hines, Illinois 60141, United States
New Orleans VAMC, New Orleans, Louisiana 70112, United States
Boston VA Medical Center, Boston, Massachusetts 02130, United States
Bronx VA Medical Center, Bronx, New York 10468, United States
Study Chairman, Bronx, New York 10468, United States
Oklahoma City VA Medical Center, Oklahoma City, Oklahoma 73104, United States
Vamc - Pittsburgh, Pittsburgh, Pa, Pittsburgh, Pennsylvania 15240-1001, United States
Dallas VA Medical Center, Dallas, Texas 75216, United States
Hunter Holmes McGuire VA Medical Center, Richmond, Virginia 23249, United States
Additional Information
Starting date: January 1998
Last updated: January 20, 2009
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