General Clinical Research Center

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and investigate the usefulness of the EEC as a predictor of the subjects response to the KD, In Phase 1, the current practices for initiation of the ketogenic diet and its efficacy (defined as >50% reduction of seizure frequency at the 3-month interval compared to baseline) will be investigated. We propose that a gradual introduction of the KD, without a 24 to 48 hour preceding fast (Grad-KD), is as safe and efficacious as the currently recommended initiation of the KD (CR-KD) with fast. Safety of the two protocols will be evaluated during a six-day inpatient admission and the first three months of exposure. Efficacy will be determined at three months. Baseline and 1- month changes in the routine electroencephalogram (EEG) will be examined simultaneously. The predictive power of the changes between the baseline and 1-month EEG for the 3-month response (defined above) will be shown in those EEG records that have diminished background slowing or reduction of potentially epileptogenic discharges. In a pilot study we will investigate the mechanistic hypothesis that the antiepileptic properties of the KD is dueto anincrease in CNS-Gamma Amino Butyric Acid (GABA), asmeasured by MRI Spectroscopy at baseline, 0.5-month and3- month in the CR-KD therapy. We will also examine the association between changes in CNS-GABA at 0.5- month andresponse to KD therapy (defined above). In Phase 2, subjects who have demonstrated a positive response at 3 months will be followed. The maintenance KD in responders on two caloric intakes will be evaluated. The currently recommended KD is hypocaloric, providing only 75% of subject's caloric needs, and does not allow any weight gain for the 12 months duration of treatment. The necessity of semi-starvation to maintain a positive clinical response has not been evaluated scientifically. We will examine if a Eucaloric KD (Eu-KD), with adequate calories for the subject allowing for normal weight gain, is as effective as the currently recommended Hypocaloric KD (Hypo-KD) with no weight gain or loss over 12 months. As part of this evaluation, comparisons of two methods used to estimate caloric needs, Recommended Daily Allowance (RDA) tables and Resting Energy Expenditure (by indirect calorimetry), will be made. In addition, the effect of the KD on several nutritional Darameters including anthropometry, body composition and bone mineral status, will be evaluated, allowing the 12-month impact of the Eu-KD versus Hypo-KD diets on nutritional status to be compared.