Vitamin E Supplementation in Hyperinsulinism/Hyperammonemia Syndrome

2019-01-15 13:04:17 | BioPortfolio


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


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.

Study Design


Hyperinsulinism-Hyperammonemia Syndrome


Vitamin E


Children's Hospital of Philadelphia
United States


Enrolling by invitation


Children's Hospital of Philadelphia

Results (where available)

View Results


Published on BioPortfolio: 2019-01-15T13:04:17-0500

Clinical Trials [2237 Associated Clinical Trials listed on BioPortfolio]

Monitoring the Hyperammonaemia:TOXicity of Drugs (AmmoTOX)

Several drugs and chemotherapies seem to have an impact on the metabolic system. This study investigates reports of metabolic toxicities such as hyperammonemia, including the International...

Utility of [F-18] fluoroDOPA for Neonatal Hyperinsulinism

Children with congenital hyperinsulinism have low blood sugar, and some of these children may require surgery. In this study, researchers affiliated with the University of Pennsylvania wil...

Compassionate Use of SOM230 for Hyperinsulinemic/Hypoglycemia

Congenital hyperinsulinism is a rare condition that can cause life-threatening hypoglycemia. Current treatment for congenital hyperinsulinism is often suboptimal, and such individuals may ...

Sandostatine® LP and Hyperinsulinism

To replace Sandostatine® in three daily subcutaneous injections by a single intramuscular injection of Sandostatine® LP per month in patients with a diffuse form of hyperinsulinism.

Sirolimus for the Treatment of Hyperinsulinism

The purpose of this pilot study is to generate data to assess feasibility of study design/procedures and for formal sample size estimation for a larger multicenter study of the efficacy an...

PubMed Articles [6004 Associated PubMed Articles listed on BioPortfolio]

Contribution of CYP27B1 and CYP24A1 Genetic Variations to the Incidence of Acute Coronary Syndrome and to Vitamin D Serum Level.

Cardiovascular diseases remain a major public health burden worldwide. It was reported that vitamin D protects the cardiovascular system through several mechanisms mainly by hindering atherosclerosis ...

Vitamin D supplementation after malnutrition associated with time-related increase of cancer diagnoses: A cohort study of 389 patients with Wernicke-Korsakoff syndrome.

Vitamin deficiencies may reflect less-than-optimal health in select populations. The aim of this study was to determine whether vitamin D supplementation (VDs) after malnutrition may be adversely rela...

Characteristics and outcomes of critically ill patients with severe hyperammonemia.

To determine the etiology and outcomes of critically ill patients with severe hyperammonemia.

Effects of vitamin D supplementation on follicular development, gonadotropins and sex hormone concentrations, and insulin resistance in induced polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) as a reproductive disorder disturbs ovarian follicular development, vitamin D stimulated insulin activity, and sex hormone concentrations. This study aimed to examine ...

Active vitamin D supplementation alleviates initiation and progression of nonalcoholic fatty liver disease by repressing the p53 pathway.

Recent studies have found vitamin D deficiency promotes fat deposition into the hepatocytes, thus contributing to the development of nonalcoholic fatty liver disease (NAFLD), which is a hepatic manife...

Medical and Biotech [MESH] Definitions

A syndrome with excessively high INSULIN levels in the BLOOD. It may cause HYPOGLYCEMIA. Etiology of hyperinsulinism varies, including hypersecretion of a beta cell tumor (INSULINOMA); autoantibodies against insulin (INSULIN ANTIBODIES); defective insulin receptor (INSULIN RESISTANCE); or overuse of exogenous insulin or HYPOGLYCEMIC AGENTS.

A lipid cofactor that is required for normal blood clotting. Several forms of vitamin K have been identified: VITAMIN K 1 (phytomenadione) derived from plants, VITAMIN K 2 (menaquinone) from bacteria, and synthetic naphthoquinone provitamins, VITAMIN K 3 (menadione). Vitamin K 3 provitamins, after being alkylated in vivo, exhibit the antifibrinolytic activity of vitamin K. Green leafy vegetables, liver, cheese, butter, and egg yolk are good sources of vitamin K.

A nutritional condition produced by a deficiency of VITAMIN D in the diet, insufficient production of vitamin D in the skin, inadequate absorption of vitamin D from the diet, or abnormal conversion of vitamin D to its bioactive metabolites. It is manifested clinically as RICKETS in children and OSTEOMALACIA in adults. (From Cecil Textbook of Medicine, 19th ed, p1406)

OXIDOREDUCTASES which mediate vitamin K metabolism by converting inactive vitamin K 2,3-epoxide to active vitamin K.

An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction.

More From BioPortfolio on "Vitamin E Supplementation in Hyperinsulinism/Hyperammonemia Syndrome"

Quick Search

Relevant Topics

Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...

Congenital Diseases
Congenital conditions are those which are present from birth. They include structural deformities or loss of function in organs such as the <!--LGfEGNT2Lhm-->heart, gut or skeletal system. They can be corrected by <!--LGfEGNT2Lhm-->surgery, m...

Pancreatic Cancer
The pancreas secretes a number of important hormones into the digestive tract and the blood stream. Cancers are most commonly exocrine than endocrine (neuroendocrine) tumors. Functional tumors secrete hormones; Insulinoma, Gastrinoma, Somatostatinoma, VI...

Searches Linking to this Trial