Vitamin E Efficacy in HI/HA

The primary objective of this study is to determine an effective dose of vitamin E to reduce protein-induced hyperinsulinemia in subjects with HI/HA syndrome. Secondary objectives are to assess the effects of vitamin E on plasma C-peptide concentrations, serum alpha-tocopherol concentrations, blood ammonia concentrations, hypoglycemic events, and seizure frequency. The effect of vitamin E on brain glutamate levels and electroencephalogram findings will be explored. This single-group open-label dose-finding clinical study will use a before-and-after design to compare clinical and laboratory data before and after 2-3 weeks of escalating doses of oral vitamin E treatment in subjects with HI/HA syndrome. This single-site outpatient study will recruit up to 5 adult participants (18 years of age or older) with HI/HA syndrome. Each study visit will consist of blood tests, an IV leucine acute insulin response (AIR) test, home glucose meter and continuous glucose monitor (CGM) review, and a symptom questionnaire. The baseline and final visits will also include electroencephalogram (EEG) and brain magnetic resonance imaging (MRI) with glutamate chemical exchange saturation transfer (GluCEST) analysis. After baseline assessments, including a 2 week run-in period of CGM use, subjects will take twice daily oral vitamin E (alpha-tocopherol) at home. After steady-state of that dose of vitamin E has been achieved (i.e. at least 2 weeks on the dose of vitamin E), subjects will return for the next study visit. If there is no dose-limiting toxicity, then the twice daily vitamin E dose will be increased, and the subjects will return for a subsequent study visit after at least 2 weeks. If there is no dose-limiting toxicity at this visit, then the twice daily vitamin E dose will be increased again, and the subjects will return for a final study visit after at least 2 weeks. If toxicity is identified at any point, vitamin E will be discontinued and final study visit procedures will be performed.