Oral Glibenclamide in Preterm Infants With Hyperglycaemia (GALOP)

Preterm Clinical Trial

— GALOP  

Official title:

Oral Glibenclamide in Preterm Infants With Hyperglycaemia (GALOP)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05687500
• Other study ID #: P160916J
• Secondary ID: 2021-005766-18
• Status: Recruiting
• Phase: Phase 2
• Start date: May 20, 2023
• Est. completion date: May 2026

Study information

• Verified date: June 2023
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Elsa KERMORVANT, Pr
• Phone: 01 71 19 61 75
• Email: elsa.kermorvant[@]aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to confirm hypothesis that Glibenclamide can be administered orally and is an alternative to insulin therapy in treating transient hyperglycemia of premature newborns.

Description:

Transient hyperglycemia of premature newborns results from an overall decrease in insulin sensitivity, which is responsible at the beta cell level for abnormalities of intragranular cleavage of proinsulin into insulin, leading to reduced active insulin secretion. Intravenous administration of exogenous insulin can be used to combat insulin resistance and lower blood glucose, but it is difficult to manage in premature newborns and is associated with a substantial risk of hypoglycemia. Glibenclamide, which stimulates endogenous insulin secretion and can be administered orally, might be an alternative to insulin therapy in treating transient hyperglycemia of premature newborns.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 45
• Est. completion date: May 2026
• Est. primary completion date: February 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 34 Weeks

Eligibility

Inclusion Criteria:

• Newborn less than 34 week of amenorrhea corrected age

• Birth weight < 1500 g

• Birth term < 32 week of amenorrhea

• Hyperglycemia = 10 mmol/l in 2 measurements, 3 hours apart after potential reduction of glucose intakes following each department's protocol

• Secure venous access point (umbilical venous catheter or epicutaneo-cava catheter)

• Enteral feeding considered before inclusion or already established

• Consent obtained from persons holding parental authority

• Beneficiary of social security

Exclusion Criteria

• Contraindication to enteral feeding (at the discretion of the clinician responsible for the child)

• Contraindication to glibenclamide according to current SPC

• Foetal growth restriction (FGR) birth weight < 3rd percentile (AUDIPOG definition)

• Severe birth defect, including cardiac malformation associated with a risk of myocardial ischemia

• Severe sepsis requiring mechanical ventilation or haemodynamic support

• Severe renal dysfunction (serum creatinine > 120 µmol/l)

• Severe hepatocellular failure (V factor less than the standard laboratory range for the age) and/or severe cholestasis (> 50 µmol/L)

• Hyperglycemia associated with an error in administering glucose infusion

• Profound hypophosphoremia (< 1 mmol/l)

• Hypersensitivity to glibenclamide or other sulphonylureas or sulphonamides, or one of the excipients

• Patient with continuous insulin IV administration

• Patient treated with miconazole

Related Conditions & MeSH terms

• Hyperglycemia
• Hypoglycemia
• Premature Birth
• Preterm

Intervention

Drug:
• Glibenclamide
Amglidia®: glibenclamide oral suspension 6 mg/ml administered by gastric tube after dilution to 1/6th in human milk

Biological:
• Pharmacokinetics study
0.2 ml blood sampling at 3 hours, 6 hours, 10 hours and 24 hours after the first administration and after 24 hours of blood glucose stabilization. PK parameters of glibenclamide will be determined using nonlinear analysis: area under the plasma concentration time curve (AUC), absorption constant ,apparent clearance and volume of distribution
• C-peptide proinsulin ratio
blood sampling at before first administration and after 24 hours for measurement of C-peptide proinsulin ratio
• Blood glucose on fluorinated tube
0.3 ml blood sampling at 3 hours, 6 hours, 10 hours and 24 hours after the first administration and after 24 hours of blood glucose stabilization.
• Routine biological monitoring
If there are not performed as part of standard care, biological monitoring of ALT, AST, complete blood count, hemostasis, urea, creatinine, blood ionogram will be done before first administration at the following time frame : 48 hours after the first administration than each days during treatment period, and 48 hours after the end of treatment.
• glycose holter monitor
glucose levels will be collected with a smarter continuous glucose monitoring system, placed on inclusion and until the end of treatment

Locations

Country	Name	City	State
France	Hopital Necker - Enfants malades	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Blood glucose control	The primary evaluation criteria is 72 hours blood glucose control on glibenclamide treatment (success of the treatment). This is defined as the non-use of insulin and absence of severe hypoglycemia (< 1.5 mmol/l) or persistent moderate hypoglycemia (< 2.6 mmol/l in 2 successive measurements (dextro) at an interval of more than 3 hours)	At 72 hours after the first administration
Secondary	Overall success of the treatment	Overall success of the treatment defined by continuation to the end of treatment without recourse to insulin.	At 36 week of amenorrhea corrected age
Secondary	Blood glucose profile on glibenclamide	Time between the start of glibenclamide treatment and the 1st blood glucose < 10 mmol/l	At the end of treatment assessed up to 15 days
Secondary	Blood glucose profile on glibenclamide	Time between the start of glibenclamide treatment and the 1st blood glucose < 8 mmol/l	At the end of treatment assessed up to 15 days
Secondary	Blood glucose profile on glibenclamide	Proportion of time spent within the target blood glucose range (= 4 and < 10 mmol/l) during the period of glibenclamide treatment	At the end of treatment assessed up to 15 days
Secondary	Blood glucose profile on glibenclamide	Proportion of time spent above the target level (= 10 mmol/l) during the period of glibenclamide treatment	At the end of treatment assessed up to 15 days
Secondary	Blood glucose profile on glibenclamide	Proportion of time spent in hypoglycemia (< 2.6 mmol/l) during the period of glibenclamide treatment	At the end of treatment assessed up to 15 days
Secondary	Duration of glibenclamide treatment	Duration of glibenclamide treatment.	At the end of treatment assessed up to 15 days
Secondary	Nutritional intakes and growth	Carbohydrate	At the end of treatment assessed up to 15 days
Secondary	Nutritional intakes and growth:	lipid	At the end of treatment assessed up to 15 days
Secondary	Nutritional intakes and growth:	protein	At the end of treatment assessed up to 15 days
Secondary	Nutritional intakes and growth:	mean caloric intake (kcal/kg/day) during treatment	At the end of treatment assessed up to 15 days
Secondary	Nutritional intakes and growth:	mean weight gain (g/kg/day)	At the end of treatment assessed up to 15 days
Secondary	Nutritional intakes and growth	Carbohydrate	At 36 week of amenorrhea corrected age
Secondary	Nutritional intakes and growth:	lipid	At 36 week of amenorrhea corrected age
Secondary	Nutritional intakes and growth:	protein	At 36 week of amenorrhea corrected age
Secondary	Nutritional intakes and growth:	mean caloric intake (kcal/kg/day) during treatment	At 36 week of amenorrhea corrected age
Secondary	Nutritional intakes and growth:	mean weight gain ((g/kg/day)	At 36 week of amenorrhea corrected age
Secondary	Number of children with episode of hypoglycemia	Number of children with at least one episode of moderate (blood glucose < 2.6 mmol/l) or severe (< 1.5 mmol/l) hypoglycemia	At 72 hours after first administration
Secondary	Number of children with episode of hypoglycemia	Number of children with at least one episode of moderate (blood glucose < 2.6 mmol/l) or severe (< 1.5 mmol/l) hypoglycemia	At the end of treatment assessed up to 15 days
Secondary	Type of adverse reactions on glibenclamide	evaluation of the type of adverse reactions identified during the study	At 36 week of amenorrhea corrected age
Secondary	Number of adverse reactions on glibenclamide	evaluation of number of adverse reactions identified during the study	At 36 week of amenorrhea corrected age
Secondary	Number of participants with co-morbidity	Neonatal morbidity assessed at 36 WA corrected age: intraventricular haemorrhage, periventricular leukomalacia, retinopathy of premature newborns, haemodynamic disorders, ulcerative necrotising enterocolitis	At 36 week of amenorrhea corrected age
Secondary	Mortality	Mortality will be assessed	At 36 week of amenorrhea corrected age
Secondary	Dose adjustment	Number of dose adjustments, to evaluate the easy of use	At the end of treatment assessed up to 15 days
Secondary	ease of use by caregivers	Assessment scores by visual-analogue scale for ease of use by caregivers; 0 as the lowest score, 10 as the highest score	At day one of treatment
Secondary	ease of use by caregivers	Assessment scores by visual-analogue scale for ease of use by caregivers; 0 as the lowest score, 10 as the highest score	At day two of treatment
Secondary	ease of use by caregivers	Assessment scores by visual-analogue scale for ease of use by caregivers; 0 as the lowest score, 10 as the highest score	At day three of treatment
Secondary	Plasma concentrations of glibenclamide	Evaluated by the pharmacokinetics study	At 3 hours after the first administration
Secondary	Plasma concentrations of glibenclamide	Evaluated by the pharmacokinetics study	At 6 hours after the first administration
Secondary	Plasma concentrations of glibenclamide	Evaluated by the pharmacokinetics study	At 10 hours after the first administration
Secondary	Plasma concentrations of glibenclamide	Evaluated by the pharmacokinetics study	At 24 hours after the first administration
Secondary	Plasma concentrations of glibenclamide	Evaluated by the pharmacokinetics study	At 24 hours of blood glucose stabilization