Glucocorticoids DeficiencyNCT02838472
Ascorbic Acid Treatment in Congenital Glucocorticoids and Mineralocorticoids Deficiency Due to NNT Mutation
A study testing Ascorbic Acid in people with Glucocorticoids Deficiency, run by Hadassah Medical Organization at 1 site in Israel.
Trial summary
Nicotinamide nucleotide transhydrogenase (NNT) mutations cause glucocorticoid and mineralocorticoid deficiencies through decreased detoxification of reactive oxygen species (ROS) in adrenocortical cells. Read more about this study
- Who is it for?
- Ages 1 year and older
- Conditions the study is for
- Glucocorticoids Deficiency
- What is being tested?
- Ascorbic Acid
- How many people
- 3 participants
- Where
- 1 siteIsrael
- Study dates
- Jun 2016to Dec 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- NNT mutation homozygous patients with glucocorticoids deficiency
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read more
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.
Read the 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.
- Conditions
- Glucocorticoids Deficiency
- Being tested
- Ascorbic Acid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ascorbic AcidDrug
Also called Vitamin C
Ascorbic acid administration at a doses of 75-80% of the upper limit of allowance according to IOM
What is being measured
The primary outcome is the main question the study is designed to answer.
glucocorticoids secretion in response to ACTH test
Measured: 1 year
basal ACTH levels
Measured: 1 year
Secondary outcomes (1)
insulin and glucose levels in OGTT
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jul 2016 (estimated)
- Study startJun 2016
- Primary completionAug 2017 (estimated)
- Study completionDec 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Glucocorticoids DeficiencyStudies of the same condition, open and under way.
- More trials run by Hadassah Medical OrganizationThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hadassah Medical Organization
- Sponsor type
- University, hospital or other
- Collaborators
- Soroka University Medical Center
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02838472
- Sponsor's protocol ID
- 0631-15-HMO
- Status last verified
- Jun 2016
- First submitted
- 17 Jul 2016
- Last updated
- 20 Jul 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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.
PubMed 22634753Institute 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/
PubMed 25077263Weinberg-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.
PubMed 26070314
Study at a glance
From the registry record, last updated by the sponsor on 20 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ascorbic Acid Treatment for Patients With Combined Mineralocorticoid and Glucocorticoid Deficiency Secondary to Nicotinamide Nucleotide Transhydrogenase Mutation
- ClinicalTrials.gov ID
- NCT02838472
- Acronym / sponsor ID
- 0631-15-HMO
- Conditions
- Glucocorticoids Deficiency
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 3 participants (estimated)
- Lead sponsor
- Hadassah Medical OrganizationUniversity, hospital or other
- Collaborators
- Soroka University Medical Center
- Study start
- Jun 2016
- Primary completion
- Aug 2017 (estimated)
- Study completion
- Dec 2017 (estimated)
- First posted
- 20 Jul 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 1 year and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- NNT mutation homozygous patients with glucocorticoids deficiency
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ascorbic AcidAlso: Vitamin CAscorbic acid administration at a doses of 75-80% of the upper limit of allowance according to IOM | Drug | – |
Primary outcome
glucocorticoids secretion in response to ACTH test
Time frame: 1 year
basal ACTH levels
Time frame: 1 year
1 secondary outcome
insulin and glucose levels in OGTT
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jul 2016.
- Background: PubMed 22634753Meimaridou 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.
- Background: PubMed 25077263Institute 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/
- Results publication: PubMed 26070314Weinberg-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.
- Individual participant dataSharing planned: No
Related trials for Glucocorticoids Deficiency
RecruitingObservational study
Adrenal Diseases in the Population of Modena: A Clinical-Epidemiological Database of Patients Referred to the Adrenal Disorders Outpatient Clinic of the Clinical Unit of Endocrinology at the Modena University Hospital (AOU Modena)
Cushing s Syndrome, Cushing Disease
Active, not recruitingObservational study
The Austrian LEAD (Lung hEart sociAl boDy) Study
Respiration Disorders, Body Composition, Beneficial
Not yet recruiting
Prevention of AIDS With Opportunistic Infection Paradoxical IRIS
HIV (Human Immunodeficiency Virus), IRIS
RecruitingObservational study
Predictive Factors for Treatment Response in Patients With Newly-diagnosed Polymyalgia Rheumatica and Giant Cell Arteritis
Polymyalgia Rheumatica (PMR), Giant Cell Arteritis (GCA)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ascorbic Acid in people with Glucocorticoids Deficiency, run by Hadassah Medical Organization at 1 site in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 20 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
glucocorticoids secretion in response to ACTH test (time frame: 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02838472, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jul 2016.