Neonatal Diabetes Secondary to Mutation in the Potassium ChannelPhase 3NEOGLINCT02375828
Glibentek in Patients With Neonatal Diabetes Secondary to Mutations in K+-ATP Channels
A Phase 3 study testing Glibenclamide in people with Neonatal Diabetes Secondary to Mutation in the Potassium Channel, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
The understanding of the molecular mechanisms of neonatal diabetes has deeply changed the therapy of patients carrying mutations in the K-ATP channel. Indeed, those patients are not treated anymore by insulin injections but by glibenclamide an oral anti-diabetic drug widely used in type 2 diabetes. Read more about this study
- Who is it for?
- Ages 1 month to 18 years
- Conditions the study is for
- Neonatal Diabetes Secondary to Mutation in the Potassium Channel
- What is being tested?
- Glibenclamide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteFrance
- Study dates
- 20 Mar 2015to 22 Jul 2019
- Phase
- Phase 3
- 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 month to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age below 18 years
- Neonatal diabetes secondary to documented mutation in one of the 2 sub units of potassium channels
- Patients already treated by glibenclamide pills
- Signed consent
Who cannot join
- Families unable to fill in the questionnaries
- Patients unable to answer to the visual hedonic squale
- Patients unable to take the oral solution
- Known allergy to sulfonylureas or to other antidiabetic or antibiotic sulfamides
- Insulin therapy associated to glibenclamide
- Miconazole therapy
Show all 11Show fewer
- Porphyria
- Breast feeding
- Severe renal failure (creatinine clearance below 30 ml/mn)
- Liver failure (prothombine time below 70)
- Not affiliated to the health care system
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Tolerance and Acceptability of Glibentek in Patients With Neonatale Diabetes Secondary to Mutations in K+-ATP Channels
The understanding of the molecular mechanisms of neonatal diabetes has deeply changed the therapy of patients carrying mutations in the K-ATP channel. Indeed, those patients are not treated anymore by insulin injections but by glibenclamide an oral anti-diabetic drug widely used in type 2 diabetes. Anyway, its galenic form (pills of 5 mg) is not suitable for children and difficult to administrate to infants or young children. The purpose of this study is to determine if a new galenic form of this durg is more suitable and as efficient as pills in children with neonatal diabetes.
Read the detailed description
Neonatal diabetes mellitus (NDM), characterized by hyperglycaemia requiring exogenous insulin therapy, is a rare condition that appears during the first months of life with an estimated incidence of 1 in 12000 newborns. We recently published that in our large cohort, the origin of the disease is an heterozygous activating mutation of the coding sequence of KCNJ11 or ABCC8 genes in 42% of patients. These genes encode for the Kir 6.2 subunit (KCNJ11 gene) and for the SUR1 subunit (ABCC8 gene) of the ATP-sensitive K+ channel (KATP) whom function in the beta cell is to induce a membrane depolarization triggering the exocytosis of insulin-containing granules. The understanding of the molecular substrate of the disease has deeply changed the therapy, allowing the switch from insulin injections to an oral medication with sulfonylureas. Indeed, these drugs specifically bind to SUR1 subunit increasing the closing ability of the KATP by an ATP-independent mechanisms stimulating insulin secretion. Together with others we demonstrated that these drugs were efficient in replacement of subcutaneous injected insulin in children or adults with a Kir6.2 or a SUR1 activating mutation allowing an excellent metabolic control of the disease without the side effects of insulin (hypoglycemia).
Anyway, in most countries, glibenclamide has not been approved for use in children by heath authorities in france and its use is then only temporary tolerated in this specific indication.
Furthermore its galenic form (pills) is not suitable for children and especially for infants. The dosage is too high for most infants and young children or children wih neurologic defects (frequently associated to this kind of neonatal diabetes) can't swallow pills. Chewing the pill can't be an alternative as sulfamides are known induce alterations of tooth enamel color.
Most patients parents have to crush the pills and dilute the powder in water before administrating it to their child. Such process doesn't follow recommendations of administration of and medicine contradiction. It can also alter the drug cinetic.as glibenclamide is not completely soluble in water.
After our successful clinical trial, we decided then to be a part in the development of a galenice form suitable for children. The AMMtek company has created a new galenic dedicated to pediatric patients. This new oral solution has been demonstrated to be safe and effective in a phase 1 study. Its pediatric investigation plan has been validated in july 2013 by the European medicine agency. The French drug and food agency (ANSM) has asked for a tolerance and acceptability study before giving its approval for use in children and infants with neonatal diabetes.
The aim of this study is then to determine the tolerance and acceptability of an oral solution of glibenclamide (Glinbentek) developed and dedicated to pediatric patients with neonatal diabetes secondary to mutation in potassium channels.
- Being tested
- Glibenclamide
- Keywords
- Acceptability, Phase 3, Neonatal diabetes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GlibenclamideDrug
Glibenclamide pills will be administrated during one month at the previously used dosage. During the first month of the study we wwil record pharmacokinetic data, number of hypoglycaemia and the administration problems associated to this galenic form. At the end of the first month of enrolment, patients will be given oral solution of glibenclamide for the 4 remaining months. Pharmacocinetic data, number of hypoglycaemia and parents and children feeling about pratictability of administration will be then recorded.
| Study group | Role | What they receive |
|---|---|---|
| Patients with neonatal diabetes | Experimental | Patients with neonatal diabetes Receives: Drug: Glibenclamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Acceptability of an oral solution of glibenclamide (Hedonic visual scale)
Hedonic visual scale
Measured: 2 months after the change from pills to oral solution.
Acceptability of an oral solution of glibenclamide (Hedonic visual scale)
Hedonic visual scale
Measured: 3 months after the change from pills to oral solution.
Secondary outcomes (7)
Tolerance of an oral solution of glibenclamide (Self administrated questionnaries)
Self administrated questionnaries, liver and renal biology
Measured: 2 months after the change from pills to oral solution.
Tolerance of an oral solution of glibenclamide (Self administrated questionnaries)
Self administrated questionnaries, liver and renal biology
Measured: 3 months after the change from pills to oral solution.
Recording pharmaceutical data on pills and oral solution of glibenclamide (Blood drug dosage)
Blood drug dosage
Measured: At inclusion
Recording pharmaceutical data on pills and oral solution of glibenclamide (Blood drug dosage)
Blood drug dosage
Measured: 2 months after the switch from pills to oral solution
No alteration in metabolic control of the disease
HbA1C at month 3, fructosamine at month 2 and 3, self record of hypoglycaemia during month 1, 2 and 3, glycemia before and after meals during 2 consecutive days at introduction of oral solution and during 2 meals at month 2 and month 3
Measured: During the first month of administration
No alteration in metabolic control of the disease
HbA1C at month 3, fructosamine at month 2 and 3, self record of hypoglycaemia during month 1, 2 and 3, glycemia before and after meals during 2 consecutive days at introduction of oral solution and during 2 meals at month 2 and month 3
Measured: 2 months after the change from pills to oral solution
No alteration in metabolic control of the disease
HbA1C at month 3, fructosamine at month 2 and 3, self record of hypoglycaemia during month 1, 2 and 3, glycemia before and after meals during 2 consecutive days at introduction of oral solution and during 2 meals at month 2 and month 3
Measured: 3 months after the change from pills to oral solution
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2015 (estimated)
- Study start20 Mar 2015
- Primary completion4 Mar 2016
- Study completion22 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Neonatal Diabetes Secondary to Mutation in the Potassium ChannelStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- URC-CIC Paris Descartes Necker Cochin
- Responsible party
- Sponsor
- Investigators
- Michel Polak, MD, PhD, Study director, Hopital Universitaire Necker Enfants Malades, Assistance publique - hôpitaux de Paris, Faculté de medicine Paris Descartes, Université Sorbonne Paris cité
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02375828
- Sponsor's protocol ID
- 2014-003436-39
- Other IDs
- 2014
- Acronym
- NEOGLI
- Status last verified
- Sep 2025
- First submitted
- 24 Feb 2015
- Last updated
- 8 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Busiah K, Drunat S, Vaivre-Douret L, Bonnefond A, Simon A, Flechtner I, Gerard B, Pouvreau N, Elie C, Nimri R, De Vries L, Tubiana-Rufi N, Metz C, Bertrand AM, Nivot-Adamiak S, de Kerdanet M, Stuckens C, Jennane F, Souchon PF, Le Tallec C, Desiree C, Pereira S, Dechaume A, Robert JJ, Phillip M, Scharfmann R, Czernichow P, Froguel P, Vaxillaire M, Polak M, Cave H; French NDM study group. Neuropsychological dysfunction and developmental defects associated with genetic changes in infants with neonatal diabetes mellitus: a prospective cohort study [corrected]. Lancet Diabetes Endocrinol. 2013 Nov;1(3):199-207. doi: 10.1016/S2213-8587(13)70059-7. Epub 2013 Sep 6.
PubMed 24622368Pearson ER, Flechtner I, Njolstad PR, Malecki MT, Flanagan SE, Larkin B, Ashcroft FM, Klimes I, Codner E, Iotova V, Slingerland AS, Shield J, Robert JJ, Holst JJ, Clark PM, Ellard S, Sovik O, Polak M, Hattersley AT; Neonatal Diabetes International Collaborative Group. Switching from insulin to oral sulfonylureas in patients with diabetes due to Kir6.2 mutations. N Engl J Med. 2006 Aug 3;355(5):467-77. doi: 10.1056/NEJMoa061759.
PubMed 16885550Babenko AP, Polak M, Cave H, Busiah K, Czernichow P, Scharfmann R, Bryan J, Aguilar-Bryan L, Vaxillaire M, Froguel P. Activating mutations in the ABCC8 gene in neonatal diabetes mellitus. N Engl J Med. 2006 Aug 3;355(5):456-66. doi: 10.1056/NEJMoa055068.
PubMed 16885549Beltrand J, Baptiste A, Busiah K, Bouazza N, Godot C, Boucheron A, Djerada Z, Gozalo C, Berdugo M, Treluyer JM, Elie C, Polak M; GLID-KIR study group. Glibenclamide oral suspension: Suitable and effective in patients with neonatal diabetes. Pediatr Diabetes. 2019 May;20(3):246-254. doi: 10.1111/pedi.12823. Epub 2019 Feb 21.
PubMed 30684309
Study at a glance
From the registry record, last updated by the sponsor on 8 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tolerance and Acceptability of Glibentek in Patients With Neonatale Diabetes Secondary to Mutations in K+-ATP Channels
- ClinicalTrials.gov ID
- NCT02375828
- Acronym / sponsor ID
- NEOGLI / 2014-003436-39
- Keywords
- Acceptability, Phase 3, Neonatal diabetes
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- URC-CIC Paris Descartes Necker Cochin
- Study start
- 20 Mar 2015 (actual)
- Primary completion
- 4 Mar 2016 (actual)
- Study completion
- 22 Jul 2019 (actual)
- First posted
- 3 Mar 2015 (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.
The understanding of the molecular mechanisms of neonatal diabetes has deeply changed the therapy of patients carrying mutations in the K-ATP channel. Indeed, those patients are not treated anymore by insulin injections but by glibenclamide an oral anti-diabetic drug widely used in type 2 diabetes. Anyway, its galenic form (pills of 5 mg) is not suitable for children and difficult to administrate to infants or young children. The purpose of this study is to determine if a new galenic form of this durg is more suitable and as efficient as pills in children with neonatal diabetes.
Detailed description
Neonatal diabetes mellitus (NDM), characterized by hyperglycaemia requiring exogenous insulin therapy, is a rare condition that appears during the first months of life with an estimated incidence of 1 in 12000 newborns. We recently published that in our large cohort, the origin of the disease is an heterozygous activating mutation of the coding sequence of KCNJ11 or ABCC8 genes in 42% of patients. These genes encode for the Kir 6.2 subunit (KCNJ11 gene) and for the SUR1 subunit (ABCC8 gene) of the ATP-sensitive K+ channel (KATP) whom function in the beta cell is to induce a membrane depolarization triggering the exocytosis of insulin-containing granules. The understanding of the molecular substrate of the disease has deeply changed the therapy, allowing the switch from insulin injections to an oral medication with sulfonylureas. Indeed, these drugs specifically bind to SUR1 subunit increasing the closing ability of the KATP by an ATP-independent mechanisms stimulating insulin secretion. Together with others we demonstrated that these drugs were efficient in replacement of subcutaneous injected insulin in children or adults with a Kir6.2 or a SUR1 activating mutation allowing an excellent metabolic control of the disease without the side effects of insulin (hypoglycemia).
Anyway, in most countries, glibenclamide has not been approved for use in children by heath authorities in france and its use is then only temporary tolerated in this specific indication.
Furthermore its galenic form (pills) is not suitable for children and especially for infants. The dosage is too high for most infants and young children or children wih neurologic defects (frequently associated to this kind of neonatal diabetes) can't swallow pills. Chewing the pill can't be an alternative as sulfamides are known induce alterations of tooth enamel color.
Most patients parents have to crush the pills and dilute the powder in water before administrating it to their child. Such process doesn't follow recommendations of administration of and medicine contradiction. It can also alter the drug cinetic.as glibenclamide is not completely soluble in water.
After our successful clinical trial, we decided then to be a part in the development of a galenice form suitable for children. The AMMtek company has created a new galenic dedicated to pediatric patients. This new oral solution has been demonstrated to be safe and effective in a phase 1 study. Its pediatric investigation plan has been validated in july 2013 by the European medicine agency. The French drug and food agency (ANSM) has asked for a tolerance and acceptability study before giving its approval for use in children and infants with neonatal diabetes.
The aim of this study is then to determine the tolerance and acceptability of an oral solution of glibenclamide (Glinbentek) developed and dedicated to pediatric patients with neonatal diabetes secondary to mutation in potassium channels.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients with neonatal diabetes | Experimental | Drug: GlibenclamidePatients with neonatal diabetes |
Who may qualify
- Ages
- 1 month to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- Age below 18 years
- Neonatal diabetes secondary to documented mutation in one of the 2 sub units of potassium channels
- Patients already treated by glibenclamide pills
- Signed consent
Key exclusion criteria (11 listed)
- Families unable to fill in the questionnaries
- Patients unable to answer to the visual hedonic squale
- Patients unable to take the oral solution
- Known allergy to sulfonylureas or to other antidiabetic or antibiotic sulfamides
- Insulin therapy associated to glibenclamide
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 |
|---|---|---|
| GlibenclamideGlibenclamide pills will be administrated during one month at the previously used dosage. During the first month of the study we wwil record pharmacokinetic data, number of hypoglycaemia and the administration problems associated to this galenic form. At the end of the first month of enrolment, patients will be given oral solution of glibenclamide for the 4 remaining months. Pharmacocinetic data, number of hypoglycaemia and parents and children feeling about pratictability of administration will be then recorded. | Drug | Patients with neonatal diabetes |
Primary outcome
Acceptability of an oral solution of glibenclamide (Hedonic visual scale)
Time frame: 2 months after the change from pills to oral solution.
Hedonic visual scale
Acceptability of an oral solution of glibenclamide (Hedonic visual scale)
Time frame: 3 months after the change from pills to oral solution.
Hedonic visual scale
7 secondary outcomes
Tolerance of an oral solution of glibenclamide (Self administrated questionnaries)
Time frame: 2 months after the change from pills to oral solution.
Tolerance of an oral solution of glibenclamide (Self administrated questionnaries)
Time frame: 3 months after the change from pills to oral solution.
Recording pharmaceutical data on pills and oral solution of glibenclamide (Blood drug dosage)
Time frame: At inclusion
Recording pharmaceutical data on pills and oral solution of glibenclamide (Blood drug dosage)
Time frame: 2 months after the switch from pills to oral solution
No alteration in metabolic control of the disease
Time frame: During the first month of administration
No alteration in metabolic control of the disease
Time frame: 2 months after the change from pills to oral solution
No alteration in metabolic control of the disease
Time frame: 3 months after the change from pills to oral solution
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Sep 2025.
- Background: PubMed 24622368Busiah K, Drunat S, Vaivre-Douret L, Bonnefond A, Simon A, Flechtner I, Gerard B, Pouvreau N, Elie C, Nimri R, De Vries L, Tubiana-Rufi N, Metz C, Bertrand AM, Nivot-Adamiak S, de Kerdanet M, Stuckens C, Jennane F, Souchon PF, Le Tallec C, Desiree C, Pereira S, Dechaume A, Robert JJ, Phillip M, Scharfmann R, Czernichow P, Froguel P, Vaxillaire M, Polak M, Cave H; French NDM study group. Neuropsychological dysfunction and developmental defects associated with genetic changes in infants with neonatal diabetes mellitus: a prospective cohort study [corrected]. Lancet Diabetes Endocrinol. 2013 Nov;1(3):199-207. doi: 10.1016/S2213-8587(13)70059-7. Epub 2013 Sep 6.
- Background: PubMed 16885550Pearson ER, Flechtner I, Njolstad PR, Malecki MT, Flanagan SE, Larkin B, Ashcroft FM, Klimes I, Codner E, Iotova V, Slingerland AS, Shield J, Robert JJ, Holst JJ, Clark PM, Ellard S, Sovik O, Polak M, Hattersley AT; Neonatal Diabetes International Collaborative Group. Switching from insulin to oral sulfonylureas in patients with diabetes due to Kir6.2 mutations. N Engl J Med. 2006 Aug 3;355(5):467-77. doi: 10.1056/NEJMoa061759.
- Background: PubMed 16885549Babenko AP, Polak M, Cave H, Busiah K, Czernichow P, Scharfmann R, Bryan J, Aguilar-Bryan L, Vaxillaire M, Froguel P. Activating mutations in the ABCC8 gene in neonatal diabetes mellitus. N Engl J Med. 2006 Aug 3;355(5):456-66. doi: 10.1056/NEJMoa055068.
- Results publication: PubMed 30684309Beltrand J, Baptiste A, Busiah K, Bouazza N, Godot C, Boucheron A, Djerada Z, Gozalo C, Berdugo M, Treluyer JM, Elie C, Polak M; GLID-KIR study group. Glibenclamide oral suspension: Suitable and effective in patients with neonatal diabetes. Pediatr Diabetes. 2019 May;20(3):246-254. doi: 10.1111/pedi.12823. Epub 2019 Feb 21.
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.
Michel Polak, MD, PhD study director
Hopital Universitaire Necker Enfants Malades, Assistance publique - hôpitaux de Paris, Faculté de medicine Paris Descartes, Université Sorbonne Paris cité
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Glibenclamide in people with Neonatal Diabetes Secondary to Mutation in the Potassium Channel, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 4 inclusion and 11 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: finished, as of the sponsor's last update on 8 Sep 2025. 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 France. 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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Acceptability of an oral solution of glibenclamide (Hedonic visual scale) (time frame: 2 months after the change from pills to oral solution.). 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 NCT02375828, which also lists 4 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 8 Sep 2025.