Ignite Creation Date:
2024-05-05 @ 11:08 AM
Last Modification Date:
2024-10-26 @ 9:06 AM
Study NCT ID:
NCT00007670
Status:
COMPLETED
Last Update Posted:
2023-10-30
First Post:
2000-12-29
Brief Title:
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
Sponsor:
US Department of Veterans Affairs
Organization:
VA Office of Research and Development
Study Overview
Official Title:
CSP 428 - Treatment of Seizures in the Elderly Population
Status:
COMPLETED
Status Verified Date:
2023-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
New onset epilepsy in the elderly occurs in 45000-50000 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
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 45000-50000 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 p00002 overall difference between the treatment groups lamotrigine558 gabapentin490 and carbamazepine355 The paired comparisons indicated significant differences between lamotrigine and carbamazepine p00001 and gabapentin and carbamazepine p0008 Consideration of reasons for early terminations indicates significant overall differences p0001 between treatment groups for early terminations due to adverse events lamotrigine121 gabapentin216 and carbamazepine310 There were significant paired comparisons for lamotrigine vs carbamazepine p00001 and lamotrigine vs gabapentin p0015 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 p005 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 p0007 The overall conclusion is that lamotrigine and gabapentin should be considered as initial therapy for older patients with newly diagnosed seizures
Rowan AJ Ramsay RE Collins JF Pryor F Boardman KD Uthman BM Spitz M Frederick T Towne A Carter GS Marks W Felicetta J Tomyanovich ML and the VA Cooperative Study 428 Group - New onset geriatric epilepsy A randomized study of gabapentin lamotrigine and carbamazepine Neurology 64 1868-1873 2005
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 45000-50000 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 p00002 overall difference between the treatment groups lamotrigine558 gabapentin490 and carbamazepine355 The paired comparisons indicated significant differences between lamotrigine and carbamazepine p00001 and gabapentin and carbamazepine p0008 Consideration of reasons for early terminations indicates significant overall differences p0001 between treatment groups for early terminations due to adverse events lamotrigine121 gabapentin216 and carbamazepine310 There were significant paired comparisons for lamotrigine vs carbamazepine p00001 and lamotrigine vs gabapentin p0015 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 p005 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 p0007 The overall conclusion is that lamotrigine and gabapentin should be considered as initial therapy for older patients with newly diagnosed seizures
Rowan AJ Ramsay RE Collins JF Pryor F Boardman KD Uthman BM Spitz M Frederick T Towne A Carter GS Marks W Felicetta J Tomyanovich ML and the VA Cooperative Study 428 Group - New onset geriatric epilepsy A randomized study of gabapentin lamotrigine and carbamazepine Neurology 64 1868-1873 2005
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None