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.

Condition	Treatment or Intervention	Phase
seizures in the elderly	Drug: Carbamazepine  Drug: Gabapentin  Drug: Lamotrigine	Phase III

Further Study Details: 

Expected Total Enrollment:  720

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 594 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.

Ages Eligible for Study:  60 Years and above,  Genders Eligible for Study:  Both

Criteria

Veterans 60 years of age or older who have new onset, unprovoked seizures of focal onset, with or without secondary generalization.

Alabama
      Birmingham VA Medical Center, Birmingham,  Alabama,  35233,  United States
Arizona
      Carl T. Hayden VA Medical Center, Phoenix,  Arizona,  85012,  United States
California
      San Francisco VAMC, San Francisco,  California,  94121,  United States
      Vamc - San Diego, San Diego, Ca, San Diego,  California,  92161,  United States
      Vamc - West Los Angeles, Los Angeles, Ca, Los Angeles,  California,  90073,  United States
Colorado
      Denver VA Medical Center, Denver,  Colorado,  80220,  United States
Florida
      Study Chairperson, Miami,  Florida,  33125,  United States
      Gainesville VA Medical Center, Gainesville,  Florida,  32608-1197,  United States
      Miami VA Medical Center, Miami,  Florida,  33125,  United States
      Vamc - Bay Pines, Fl, Bay Pines,  Florida,  33744,  United States
Illinois
      Edward Hines Jr. VA Hospital, Hines,  Illinois,  60141,  United States
      Chicago VA Medical Center (West Side), Chicago,  Illinois,  60612,  United States
Louisiana
      New Orleans VAMC, New Orleans,  Louisiana,  70112,  United States
Massachusetts
      Boston VA Medical Center, Boston,  Massachusetts,  02130,  United States
New York
      Study Chairman, Bronx,  New York,  10468,  United States
      Bronx VA Medical Center, Bronx,  New York,  10468,  United States
Oklahoma
      Oklahoma City VA Medical Center, Oklahoma City,  Oklahoma,  73104,  United States
Pennsylvania
      Vamc - Pittsburgh, Pittsburgh, Pa, Pittsburgh,  Pennsylvania,  15240-1001,  United States
Texas
      Dallas VA Medical Center, Dallas,  Texas,  75216,  United States
Virginia
      Hunter Holmes McGuire VA Medical Center, Richmond,  Virginia,  23249,  United States

Study ID Numbers:  428
Record last reviewed:  January 2004
Last Updated:  October 13, 2004
Record first received:  December 29, 2000
ClinicalTrials.gov Identifier:  NCT00007670
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08