Efficacy and Safety of Ketogenic Diet as Adjunctive Treatment in Adults With Refractory Epilepsy

The goal of the present open label study is to obtain pilot data to evaluate the efficacy and
safety of KD in adults with intractable epilepsy. Investigators will evaluate the effect of
KD on seizure frequency and on adverse events. Investigators will also evaluate serum levels
of the ketone body, βhydroxybutyrate (BOH) and of glucose in order to determine whether
changes in serum levels of these substances correlate with KD-associated changes in seizure
frequency. The data from the present study will be used to design a large randomized study.

Laboratory evaluations will include complete blood count (CBC), serum electrolytes, including
calcium, phosphate and magnesium, renal and liver functions, including total protein and
albumin, uric acid, fasting serum lipid profile, glucose and b- hydroxybutyrate (BOH) levels,
serum carnitine level, serum a.m. trough antiepilepsy drugs levels, and urine calcium and
creatinine level. They will be obtained twice at baseline a month apart and monthly during KD
treatment.

Primary outcome measures will include average monthly seizure frequency and adverse events.
Secondary outcome measures will include treatment compliance, quality of life questionnaire
(QOLIE-31-P) scores, and Epworth Sleepiness Scale scores.

Inclusion Criteria:

1. Age 18-65

2. Stable epilepsy, either primary generalized or localization-related with partial
complex seizures including partial complex seizures with or without secondary
generalization, partial simple seizures with a clear motor component with or without
secondary generalization, and partial simple seizures with secondary generalization;
primary generalized tonic clonic seizures; and absence seizures of > 10 sec duration.

3. Stable AED doses for at least 30 days

4. Epilepsy duration for > 1 year

5. Past/current treatment with > 3 AEDs. Vagal nerve stimulation treatment will be
allowed and will not count as an AED. Vagal nerve stimulation setting must be stable
for 3 months prior to enrollment

6. Seizure frequency of > 0.5/month

Exclusion Criteria:

1. Exclusively myoclonic seizures or absence seizures of ≤ 10 sec duration; simple
partial seizures without motor components or secondary generalization

2. Non-epileptic seizures

3. Progressive neurological disease including neoplasm, central nerve system degenerative
disorders including Alzheimer's disease, other forms of dementia

4. Any systemic illness or unstable medical condition that might pose additional risk,
including: renal or liver disease, past history of renal calculi, hyperuricemia,
hypercalcemia, mitochondrial disease, known disorder of fatty acid metabolism,
porphyria, other unstable metabolic or endocrine disturbances, and active systemic
cancer

5. Familial hyperlipidemia or uncontrolled hyperlipidemia

6. Body Mass Index (BMI) < 18

7. Change in the dose of any Antiepileptic Drug within 30 days prior to enrollment

8. Psychosis within six months of enrollment.

9. Active drug or alcohol dependence or any other factors that, in the opinion of the
site investigators would interfere with adherence to study requirements;

10. Pregnancy

11. Use of any CNS-active investigational drugs within 3 months of enrollment.

12. Inability or unwillingness of subject or legal guardian/representative to give written
informed consent.