Glucocorticoids Deficiency Clinical Trial
Official title:
Ascorbic Acid Treatment for Patients With Combined Mineralocorticoid and Glucocorticoid Deficiency Secondary to Nicotinamide Nucleotide Transhydrogenase Mutation
Nicotinamide nucleotide transhydrogenase (NNT) mutations cause glucocorticoid and
mineralocorticoid deficiencies through decreased detoxification of reactive oxygen species
(ROS) in adrenocortical cells.
Ascorbic acid is well known by its high antioxidant activity due to the neutralization of
free radicals and other reactive oxygen species.
Preliminary results of NNT_p.G200S homozygous fibroblasts' treatment with 10 micro molar
L-ascorbic acid shows significant improvement in mitochondrial morphology and in ROS
content.
The aim of this study is to figure out if ascorbic acid treatment improves the phenotype of
NNT patients by reducing ROS in their adrenocortical cells and preventing their apoptosis.
Most cases of familial glucocorticoid and mineralocorticoid deficiency are caused by
mutations interrupting steroidogenesis such as 21- hydroxylase deficiency. Recently,
nicotinamide nucleotide transhydrogenase (NNT) mutations were found to cause isolated
glucocorticoid deficiency or combined mineralocorticoid and glucocorticoid deficiency
through decreased detoxification of reactive oxygen species (ROS) in adrenocortical cells.
NNT mutation in mice causes also glucose intolerance. Ascorbic acid is an essential
water-soluble vitamin with excellent reducing properties, well known by its high antioxidant
activity due to the neutralization of free radicals and other reactive oxygen species. This
vitamin acts as the first line of defense during oxidative stress in the human body.
Ascorbic acid treatment for variant disease (e.g. - cancer, type 2 diabetes, anxiety,
depression, asthma and cardiovascular diseases) have been meticulously studies with no major
adverse effects.
In a previous study, the investigators demonstrated a higher ROS levels, a lower ATP content
and a change in mitochondrial morphology in NNT_p.G200S homozygous fibroblasts compared with
control fibroblasts.
Preliminary results of NNT_p.G200S homozygous fibroblasts' treatment with 10 micro molar
L-ascorbic acid shows significant improvement in mitochondrial morphology and in ROS
content.
The aim of this study is to figure out if ascorbic acid treatment improves the phenotype of
NNT patients by reducing ROS in their adrenocortical cells and preventing their apoptosis.
During the study NNT_p.G200S homozygous patients (no.-3) will be hospitalised for ACTH and
OGTT tests and start ascorbic acid treatment at a doses of 75-80% of the upper limit of
allowance according to IOM. ACTH and OGTT will be repeated 6 months later to assess
improvement in glucocorticoids production and insulin resistance.
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Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment