NCT03797222

Vitamin E Supplementation in Hyperinsulinism/Hyperammonemia Syndrome

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 14 (actual)
• Sponsor: Elizabeth A Rosenfeld · Academic / Other
• Sex: All
• Age: 1 Year – 40 Years
• Healthy volunteers: Not accepted

Summary

Investigators will assess the tolerability of oral Vitamin E supplementation in subjects with congenital hyperinsulinism (HI) and hyperammonemia (HA) syndrome.

Detailed description

Congenital hyperinsulinism (HI) is a rare disorder of pancreatic beta cell insulin secretion that causes persistent and severe hypoglycemia starting at birth. Hyperinsulinism/hyperammonemia (HI/HA) syndrome is the second most common type of congenital HI and is caused by activating mutations in glutamate dehydrogenase (GDH). Patients with HI/HA exhibit fasting hyperinsulinemic hypoglycemia, protein-induced hypoglycemia, hyperammonemia, seizures, and intellectual disability independent of hypoglycemia. These effects result from abnormal GDH activity in the beta cells, liver and kidney cells, neurons, and astrocytes. The only available treatment for HI/HA syndrome is diazoxide, which acts on the beta cells to decrease insulin secretion but has no effect on GDH activity itself or on other cell types. Thus, there remains a significant unmet need for improved therapies for this disorder. Preliminary data show that Vitamin E (alpha-tocopherol) inhibits GDH activity in cell lines and improves hypoglycemia in a GDH HI mouse model. Based on these preclinical studies, Investigators hypothesize that Vitamin E will inhibit GDH activity and may impact hyperinsulinemic hypoglycemia and hyperammonemia in subjects with HI/HA syndrome. This hypothesis will be tested in a future study. In this initial pilot study, investigators will assess the tolerability of oral Vitamin E supplementation in subjects with HI/HA syndrome.

Conditions

• Hyperinsulinism-Hyperammonemia Syndrome

Interventions

Type	Name	Description
DIETARY_SUPPLEMENT	Vitamin E	Subjects will take an oral Vitamin E (alpha-tocopherol) supplement once daily with a fat-containing meal for 2 weeks. The dose will be based on subject age (150 IU if 1-3 years old, 300 IU if 4-8 years old, 450 IU if 9-17 years old, 600 IU if \>17 years old). Formulations include 50 IU/mL liquid and 200 IU capsules. The liquid formulation will be used for subjects who will receive \<600 IU daily, or for any subjects who prefer liquid medication to capsules.

Timeline

• Start date: 2019-04-15
• Primary completion: 2020-03-23
• Completion: 2020-03-23
• First posted: 2019-01-09
• Last updated: 2022-11-25
• Results posted: 2022-11-25

Locations

1 site across 1 country: United States