Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT00007670 |
| Other study ID # |
428 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 3
|
| First received |
|
| Last updated |
|
| Start date |
January 1998 |
| Est. completion date |
March 2003 |
Study information
| Verified date |
October 2023 |
| Source |
VA Office of Research and Development |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
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
