Ignite Creation Date:
2024-05-06 @ 8:51 AM
Last Modification Date:
2024-10-26 @ 12:06 PM
Study NCT ID:
NCT02838472
Status:
UNKNOWN
Last Update Posted:
2016-07-20
First Post:
2016-07-17
Brief Title:
Ascorbic Acid Treatment in Congenital Glucocorticoids and Mineralocorticoids Deficiency Due to NNT Mutation
Sponsor:
Hadassah Medical Organization
Organization:
Hadassah Medical Organization
Study Overview
Official Title:
Ascorbic Acid Treatment for Patients With Combined Mineralocorticoid and Glucocorticoid Deficiency Secondary to Nicotinamide Nucleotide Transhydrogenase Mutation
Status:
UNKNOWN
Status Verified Date:
2016-06
Last Known Status:
ENROLLING_BY_INVITATION
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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_pG200S 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
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_pG200S 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
Detailed Description:
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 eg - 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_pG200S homozygous fibroblasts compared with control fibroblasts
Preliminary results of NNT_pG200S 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_pG200S 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
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 eg - 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_pG200S homozygous fibroblasts compared with control fibroblasts
Preliminary results of NNT_pG200S 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_pG200S 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None