NCT02838472

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
3

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started Jun 2016

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 1, 2016

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

July 17, 2016

Completed
3 days until next milestone

First Posted

Study publicly available on registry

July 20, 2016

Completed
1 year until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2017

Completed
4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2017

Completed
Last Updated

July 20, 2016

Status Verified

June 1, 2016

Enrollment Period

1.2 years

First QC Date

July 17, 2016

Last Update Submit

July 19, 2016

Conditions

Glucocorticoids Deficiency

Outcome Measures

Primary Outcomes (2)

  • glucocorticoids secretion in response to ACTH test

    1 year

  • basal ACTH levels

    1 year

Secondary Outcomes (1)

  • insulin and glucose levels in OGTT

    1 year

Interventions

Ascorbic AcidDRUG

Ascorbic acid administration at a doses of 75-80% of the upper limit of allowance according to IOM

Also known as: Vitamin C

Eligibility Criteria

Age1 Year+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • NNT mutation homozygous patients with glucocorticoids deficiency

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Hadassah medical center

Jerusalem, Israel, 99305, Israel

Location

Related Publications (3)

  • 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.

    PMID: 22634753BACKGROUND

  • Institute of Medicine (US) Panel on Dietary Antioxidants and Related Compounds. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington (DC): National Academies Press (US); 2000. Available from http://www.ncbi.nlm.nih.gov/books/NBK225483/

    PMID: 25077263BACKGROUND

  • Weinberg-Shukron A, Abu-Libdeh A, Zhadeh F, Carmel L, Kogot-Levin A, Kamal L, Kanaan M, Zeligson S, Renbaum P, Levy-Lahad E, Zangen D. Combined mineralocorticoid and glucocorticoid deficiency is caused by a novel founder nicotinamide nucleotide transhydrogenase mutation that alters mitochondrial morphology and increases oxidative stress. J Med Genet. 2015 Sep;52(9):636-41. doi: 10.1136/jmedgenet-2015-103078. Epub 2015 Jun 12.

    PMID: 26070314RESULT

MeSH Terms

Interventions

Ascorbic Acid

Intervention Hierarchy (Ancestors)

Sugar AcidsAcids, AcyclicCarboxylic AcidsOrganic ChemicalsHydroxy AcidsCarbohydrates

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 17, 2016

First Posted

July 20, 2016

Study Start

June 1, 2016

Primary Completion

August 1, 2017

Study Completion

December 1, 2017

Last Updated

July 20, 2016

Record last verified: 2016-06

Data Sharing

IPD Sharing
Will not share

Locations

IL(1)