Epilepsy
Conditions
Keywords
epilepsy, cardiac risk factors, memory, cognition, n-3 fatty acids, fish oil, EPA, DHA, seizures
Brief summary
The purpose of this study is to determine if Omega-3 fatty acids reduce seizures and modify cardiac risk factors in people with epilepsy.
Detailed description
Epilepsy is a common and disabling condition, characterized by recurrent seizures. Sudden unexpected death (SUDEP) is a major cause of mortality in people with epilepsy. SUDEP accounts for up to 20% of all cause mortality, and is most common in younger people, especially in their 20's to 40's year olds. In those with drug resistant epilepsy, SUDEP is five times more common than in well-controlled epilepsy. Likely causes of death include cardiac arrhythmias due to impaired autonomic regulation and reduced heart rate variability. Similarly, patients with recent myocardial infarction and congestive heart failure are at higher risk for sudden death, and manifest markedly reduced heart rate variability. Clinical studies of heart disease indicate that n-3 fatty acids, prevent cardiac arrhythmias, reduce mortality after myocardial infarction, and reduce the risk of sudden cardiac death. The mechanism by which EPA and DHA exert their anti-arrhythmia effect is due to inactivation of high frequency sodium and L-type calcium channels in the heart. In addition, n-3 fatty acids improve HRV in cardiac patients, and this reduction in HRV is postulated to be a marker of the anti-arrhythmic effect of n-3 fatty acids. Preliminary data from our group indicates that n-3 fatty acids improve HRV in people with epilepsy, especially those with low HRV (SDNN \< 50). The commonality between n-3 fatty acids and improvement in HRV in patients with heart disease and epilepsy serves as a basis for our hypothesis that n-3 fatty acids may reduce the risk of SUDEP in epilepsy. The purpose of this proposal is to determine if n-3 fatty acids reduce seizures and modify cardiac risk in people with epilepsy who are at risk of SUDEP.
Interventions
DRUGPlacebo
corn oil (n-6 fatty acids)
n-3 fatty acids, 1060 mg EPA + DHA
n-3 fatty acids, 2160 mg EPA + DHA
Sponsors
National Center for Complementary and Integrative Health (NCCIH)
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Male or female, age 18 - 70 * History of intractable localization related/partial onset seizures and generalized tonic/clonic or tonic seizures defined according to International League Against Epilepsy (ILAE) classification as: * A history compatible with localization related partial epilepsy * A history of generalized tonic clonic or tonic seizures with loss of consciousness * Three or more simple partial, complex partial or tonic-clonic seizures per month * An EEG and/or an MRI consistent with a localization related epilepsy * Evidence of at least three seizures per month for at least two months prior to the study * Exposure to at least one antiepileptic drug at adequate dose
Exclusion criteria
* Significant or progressive medical, cardiac, or other illness * Allergy to fish products or fish oil * History of a coagulation disorder * History of non-epileptic seizures * Consumption of Fish Oil at any time 30 days or less prior to enrollment * Any change in antiepileptic drugs for 30 days or less prior to enrollment * Treatment with Warfarin for 30 days or less prior to enrollment * Previous poor compliance with therapy * Drug or alcohol abuse * Uncountable seizures as a result of seizure clustering, or inadequate supervision if the patient cannot count their own seizures. * Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Seizure Frequency | Study completion (42 weeks) | Seizure frequency (seizures per day or seizures per month) |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited from the local epilepsy society, and from flyers posted in the epilepsy clinic at UCLA, and from referrals within the UCLA Department of Neurology
Participants by arm
| Arm | Count |
|---|---|
| Baseline The study began on Visit 1 when baseline data was collected and Intervention 1 was initiated. | 24 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| First Intervention (10 Weeks) | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 1 |
| First Intervention (10 Weeks) | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 | 0 |
| Third Intervention (10 Weeks) | Death | 0 | 0 | 0 | 1 | 0 | 0 |
| Washout (6 Weeks) | Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Baseline |
|---|---|
| Age, Continuous | 33.04 years STANDARD_DEVIATION 10.33 |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 20 | 0 / 20 | 0 / 22 |
| serious Total, serious adverse events | 1 / 20 | 0 / 20 | 0 / 22 |
Outcome results
Primary
Seizure Frequency
Seizure frequency (seizures per day or seizures per month)
Time frame: Study completion (42 weeks)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Seizure Frequency | 0.655 Seizures per Day | Standard Error 0.153 |
| Fish Oil Low Dose | Seizure Frequency | 0.435 Seizures per Day | Standard Error 0.097 |
| Fish OIl High Dose | Seizure Frequency | 0.631 Seizures per Day | Standard Error 0.163 |