Ascorbic Acid Treatment in Congenital Glucocorticoids and... | NCT02838472

Studies
Ascorbic Acid Treatment in Congenital Glucocorticoids and Mineralocorticoids Deficiency Due to NNT Mutation

NCT02838472

Sponsor

Hadassah Medical Organization

Status

Unknown status

Last Update Posted

Jul 20, 2016Estimated

Enrollment

3Estimated

Phase

Not Applicable

Conditions

Glucocorticoids Deficiency

Interventions

Ascorbic Acid

Countries

Israel

Protocol Section

Identification Module Status Module Sponsor/Collaborators Module Oversight Module Description Module Conditions Module Design Module Arms/Interventions Module Outcomes Module Eligibility Module Contacts/Locations Module References Module IPD Sharing Statement Module

Results Section

Participant Flow Module Baseline Characteristics Module Outcome Measures Module Adverse Events Module More Info Module

Annotation Section

Annotation Module

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module Condition Browse Module Intervention Browse Module

Protocol Section

Identification Module

NCT ID

Results Section

No data available

No data is available for this block.

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Version Holder

Status Module

Record Verification Date

Jun 2016

Overall Recruitment Status or Expanded Access Status

Unknown status

Last Known Status

Enrolling by invitation

Delayed Posting

Not provided

Why Stopped

Not provided

Expanded Access Info

Start Date

Jun 2016

Primary Completion Date

Aug 2017Estimated

Completion Date

Dec 2017Estimated

First Submitted Date

Jul 17, 2016

First Submission Date that Met QC Criteria

Jul 19, 2016

First Posted Date

Jul 20, 2016Estimated

Results Waived

Not provided

Results First Submitted Date

Not provided

Results First Submitted that Met QC Criteria

Not provided

Results First Posted Date

Not provided

Certification/Extension (aka Delayed Results) First Submitted Date

Not provided

Certification/Extension First Submitted that Passed QC Review

Not provided

Certification/Extension First Posted Date

Not provided

Last Update Submitted Date

Jul 19, 2016

Last Update Posted Date

Jul 20, 2016Estimated

Name	Class
Soroka University Medical Center	OTHER

Oversight Module

Has Data Monitoring Committee (DMC)

Is FDA Regulated Drug

Not provided

Is FDA Regulated Device

Not provided

Is Unapproved Device

Not provided

Pediatric Postmarket Surveillance of a Device Product

Not provided

Product Exported from US

Not provided

FDAAA801 Violation

Not provided

Description Module

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_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.

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 (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.

Design Module

Study Type

Interventional

Number of References to an Expanded Access Study

Not provided

Expanded Access Types

Not provided

Patient Registry

Not provided

Target Follow-Up Duration

Not provided

Phases

Not Applicable

Interventional Study Design

Allocation

Biospecimen

No data available

No data is available for this block.

Enrollment

3Estimated

Arms/Interventions Module

Arm Groups

Not provided

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Ascorbic Acid	Drug	Ascorbic acid administration at a doses of 75-80% of the upper limit of allowance according to IOM		Vitamin C

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
glucocorticoids secretion in response to ACTH test		1 year
basal ACTH levels		1 year

Secondary Outcomes

Measure	Description	Time Frame
insulin and glucose levels in OGTT		1 year

Other Outcomes

Not provided

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

NNT mutation homozygous patients with glucocorticoids deficiency

Accepts Healthy Volunteers

Sex

All

Sex/Gender Based

Not provided

Sex/Gender Description

Not provided

Minimum Age

1 Year

Maximum Age

Not provided

Standard Ages

ChildAdultOlder Adult

Study Population

Not provided

Sampling Method

Not provided

Contacts/Locations Module

Central Contacts

Not provided

Overall Officials

Not provided

Locations

Facility	Status	City	State	ZIP	Country	Contacts
Hadassah medical center		Jerusalem	Israel	99305	Israel

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
22634753	Background	Meimaridou E, Kowalczyk J, Guasti L, Hughes CR, Wagner F, Frommolt P, Nurnberg P, Mann NP, Banerjee R, Saka HN, Chapple JP, King PJ, Clark AJ, Metherell LA. Mutations in NNT encoding nicotinamide nucleotide transhydrogenase cause familial glucocorticoid deficiency. Nat Genet. 2012 May 27;44(7):740-2. doi: 10.1038/ng.2299.
25077263

ID	Term
D013400	Sugar Acids
D000144	Acids, Acyclic
D002264	Carboxylic Acids
D009930	Organic Chemicals