Ignite Creation Date:
2024-06-16 @ 11:48 AM
Last Modification Date:
2024-10-26 @ 3:30 PM
Study NCT ID:
NCT06422494
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-05-22
First Post:
2024-05-08
Brief Title:
The Role of the Adrenergic System in Hypoglycaemia Induced Inflammatory Response in People With Type 1 Diabetes and People Without Type 1 Diabetes-RAID-II
Sponsor:
Radboud University Medical Center
Organization:
Radboud University Medical Center
Study Overview
Official Title:
The Role of the Adrenergic System in Hypoglycaemia Induced Inflammatory Response in People With Type 1 Diabetes and People Without Type 1 Diabetes-RAID-II
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
RAID-II
Brief Summary:
The goal of this trial is to study the effect that adrenaline has on the immune reaction seen during a low blood sugar People with type 1 diabetes do not produce their own insulin The cells in the pancreas that produce insulin are destroyed People with type 1 diabetes require daily insulin administration As a consequence of this insulin therapy the blood sugar can dip too low causing symptoms such as confusion irritation and tiredness This is called hypoglycaemia Hypoglycaemia has been associated with an increased risk for cardiovascular disease such as heart attacks During hypoglycaemia the immune system is activated The immune system consists of white blood cells which produce cytokines these are proteins used to kill pathogens such as bacteria During hypoglycaemia there are no pathogens but the cytokines are still produced leading to unwanted damage A previous study performed by our research group showed that the immune system activation caused by hypoglycaemia is associated with the stress hormone adrenaline Adrenaline is released by the body in moments of stress such as during running or bungee jumping Adrenaline is also released by the body during hypoglycaemia to increase the sugar level Our hypothesis is that adrenaline activates the immune system during hypoglycaemia Adrenaline acts in the body through two receivers these are called alpha and beta receptors These are present on almost all cells in the body especially on the immune cells With the study we want to study the situation where there is a hypoglycaemia without the adrenaline We will achieve this by lowering the blood sugar in participants During the low blood sugar we will administer two drugs which will attach themselves to the adrenaline receivers the alpha and beta receptor With this method we hope to block the adrenaline effects and with that block the immune response caused by adrenaline
Detailed Description:
Rationale Hypoglycaemia has shown to cause a sustained pro-inflammatory response which could promote a pro-atherogenic state and explain the association between hypoglycaemia and cardiovascular events This pro-inflammatory response has been linked to the adrenaline response to hypoglycaemia Adrenergic blockade with α and β adrenergic receptor antagonists ARA has shown to blunt the leukocyte response after hypoglycaemia induction and adrenaline administration Whether and to what degree a combined blockade blunts the hypoglycaemia induced pro-inflammatory response is unknown
Objective to examine the effect of adrenergic inhibition on the hypoglycaemia induced inflammatory response eg leukocyte phenotype cytokines inflammatory proteins by performing a hyperinsulinaemic hypoglycaemic glucose clamp alongside infusion of α-ARA and β-ARA Secondary objectives consist of the effect of adrenergic blockade during hypoglycaemia on atherogenic parameters and glucose metrics eg time in range
Study design Intervention study with a cross-over design
Study population Potentially eligible adult 16 - 75 years participants will be recruited through social media the Radboudumc outpatient clinic and other advertisements We will recruit a total of 24 individuals ie 12 healthy participants and 12 participants with type 1 diabetes Participants with type 1 diabetes will be twice as there are two investigational days equipped with a blinded continuous glucose monitoring device CGM during the test which will measure interstitial glucose levels for a total of 10 days
Intervention All participants will undergo a hyperinsulinaemic hypoglycaemic glucose clamp nadir 28 mmolL During the clamp the participants will be randomized to receive an infusion of saline or an infusion of phentolamine and propranolol This will be done using a cross-over design The participants will undergo both the saline and adrenergic blockade
Main study parametersendpoints The main study parameter will be the monocyte count after 60 minutes hyperinsulinaemic hypoglycaemic clamp and adrenergic blockade during the clamp
Objective to examine the effect of adrenergic inhibition on the hypoglycaemia induced inflammatory response eg leukocyte phenotype cytokines inflammatory proteins by performing a hyperinsulinaemic hypoglycaemic glucose clamp alongside infusion of α-ARA and β-ARA Secondary objectives consist of the effect of adrenergic blockade during hypoglycaemia on atherogenic parameters and glucose metrics eg time in range
Study design Intervention study with a cross-over design
Study population Potentially eligible adult 16 - 75 years participants will be recruited through social media the Radboudumc outpatient clinic and other advertisements We will recruit a total of 24 individuals ie 12 healthy participants and 12 participants with type 1 diabetes Participants with type 1 diabetes will be twice as there are two investigational days equipped with a blinded continuous glucose monitoring device CGM during the test which will measure interstitial glucose levels for a total of 10 days
Intervention All participants will undergo a hyperinsulinaemic hypoglycaemic glucose clamp nadir 28 mmolL During the clamp the participants will be randomized to receive an infusion of saline or an infusion of phentolamine and propranolol This will be done using a cross-over design The participants will undergo both the saline and adrenergic blockade
Main study parametersendpoints The main study parameter will be the monocyte count after 60 minutes hyperinsulinaemic hypoglycaemic clamp and adrenergic blockade during the clamp
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None