Study: NCT06422494

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: hyperinsulinaemic hypoglycaemic clamp
Description: Insulin will be infused at a continuous rate of 60 mU∙m-2 ∙min-1 and glucose 20% will be infused at a variable rate, aiming for stable plasma glucose levels of 5.0 mmol/L. The infusion rate of glucose will be adjusted by plasma glucose levels, measured at 5-minute intervals. After 30 minutes of stable euglycaemia, plasma glucose levels will be allowed to drop gradually to 2.8 mmol/L and will be maintained at this level for 60 minutes. Then, insulin infusion and adrenergic blockade infusions will be stopped. Glucose infusion will be increased and then tapered until stable euglycaemia plasma levels are reached.

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: hyperinsulinaemic hypoglycaemic clamp
Description: Insulin will be infused at a continuous rate of 60 mU∙m-2 ∙min-1 and glucose 20% will be infused at a variable rate, aiming for stable plasma glucose levels of 5.0 mmol/L. The infusion rate of glucose will be adjusted by plasma glucose levels, measured at 5-minute intervals. After 30 minutes of stable euglycaemia, plasma glucose levels will be allowed to drop gradually to 2.8 mmol/L and will be maintained at this level for 60 minutes. Then, insulin infusion and adrenergic blockade infusions will be stopped. Glucose infusion will be increased and then tapered until stable euglycaemia plasma levels are reached.

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Propranolol Hydrochloride 1 MG/ML
Description: When euglycaemic level of 5.0mmol/L is achieved we will start the adrenergic blockade which will continue throughout euglycaemia and hypoglycaemia. The participants will be administered a bolus of phentolamine of 70µg/kg followed by a dose of 7.0µg/kg/min continuous infusion and a bolus of propranolol of 14µg/kg followed by a dose of 1.4µg/kg/min.

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Propranolol Hydrochloride 1 MG/ML
Description: When euglycaemic level of 5.0mmol/L is achieved we will start the adrenergic blockade which will continue throughout euglycaemia and hypoglycaemia. The participants will be administered a bolus of phentolamine of 70µg/kg followed by a dose of 7.0µg/kg/min continuous infusion and a bolus of propranolol of 14µg/kg followed by a dose of 1.4µg/kg/min.

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Phentolamine
Description: When euglycaemic level of 5.0mmol/L is achieved we will start the adrenergic blockade which will continue throughout euglycaemia and hypoglycaemia. The participants will be administered a bolus of phentolamine of 70µg/kg followed by a dose of 7.0µg/kg/min continuous infusion and a bolus of propranolol of 14µg/kg followed by a dose of 1.4µg/kg/min.

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Phentolamine
Description: When euglycaemic level of 5.0mmol/L is achieved we will start the adrenergic blockade which will continue throughout euglycaemia and hypoglycaemia. The participants will be administered a bolus of phentolamine of 70µg/kg followed by a dose of 7.0µg/kg/min continuous infusion and a bolus of propranolol of 14µg/kg followed by a dose of 1.4µg/kg/min.