Role of Adrenaline in in the Inflammatory Response in Diabetes

Hypoglycemia Clinical Trial

— RAID  

Official title:

Role of Adrenaline in the Inflammatory Response in People With Diabetes Mellitus Type 1, and Healthy Individuals

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05990933
• Other study ID #: 114664
• Status: Not yet recruiting
• Phase: N/A
• Start date: September 2023
• Est. completion date: October 2024

Study information

• Verified date: August 2023
• Source: Radboud University Medical Center
• Contact: Ilyas Mustafajev, MD
• Phone: +31683358037
• Email: ilyas.mustafajev[@]radboudumc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary aim of the present study is to study the effect of adrenaline administration on inflammatory parameters (e.g. leukocyte phenotype, cytokines, inflammatory proteins). Secondary objectives consist of the effect of adrenaline on atherogenic parameters. - All participants will receive intravenous infusion of adrenaline for an hour - We will draw blood at 7 time points, not including screening - Participants will be asked to return for a total of 4 times Researchers will compare 2 groups, healthy individuals versus people with diabetes type 1 to see if the inflammatory reaction to adrenaline differs between these two groups.

Description:

Objective: The primary aim of the present study is to study the effect of adrenaline administration on inflammatory parameters (e.g. leukocyte phenotype, cytokines, inflammatory proteins). Secondary objectives consist of the effect of adrenaline on atherogenic parameters. Potentially eligible adult ( 16 - 75 years) participants will be recruited from the diabetes clinic at the department of internal medicine from the Radboud University Medical Center. Healthy participants will be recruited through social media and other advertisements. Researchers will recruit a total of 30 individuals, i.e. 15 healthy participants and 15 people with type 1 diabetes. Participants with type 1 diabetes will be 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 receive intravenous infusion of adrenaline at a rate of 0.04ug/kg/min for 1 hour. We will draw blood at baseline, 30 minutes, 60 minutes, 180 minutes, 24 hours 72 hours and a week after start of infusion. The blood samples will be used for phenotyping of the innate immune system and measuring inflammatory and atherogenic parameters. Throughout the infusion, vital parameters will be monitored.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: October 2024
• Est. primary completion date: October 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 16 Years to 75 Years

Eligibility

Overall inclusion criteria:

• Ability to provide written informed consent
• Body-Mass Index: 19-30kg/m2
• Age =16 years, = 75 years
• Blood pressure: <140/90 mmHg
• Non-smoking
• Electrocardiogram not showing any serious arrythmia's (PVC's and PAC's accepted)

Diabetes group specific criteria:

• Insulin treatment according to basal-bolus insulin regimen (injections or insulin pump)
• Duration of diabetes > 1 year
• HbA1c < 100 mmol/mol,

Exclusion Criteria:

• - Any event of cardiovascular disease in the past 5 years (e.g. myocardial infarction, stroke, heart failure, symptomatic peripheral arterial disease)
• Pregnancy or breastfeeding or unwillingness to undertake measures for birth control
• Epilepsy,
• Current treatment with Alpha or beta blockers ( doxazosin, propranolol)
• History of panic disorders
• History of Arrhythmias
• Use of immune-modifying drugs or antibiotics
• Use of tricyclic antidepressants or MAO inhibitors
• Use of statins (e.g. stop statins >2 weeks before performing blood sampling.
• Any infection with systemic symptoms in past 2 weeks
• Previous vaccination in the past 2 weeks
• Proliferative retinopathy
• Nephropathy with an estimated glomerular filtration rate (by MDRD) ?60ml/min/1.73m2
• Overt impaired hypoglycaemic awareness assed by the Clarke Questionnaire 4 or higher

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Diabetes type1
• Hypoglycemia
• Inflammatory Response

Intervention

Drug:
• Adrenaline
Adrenaline infusion at a rate of 0.04ug/kg/min for 1 hour administered intravenously.

Locations

Country	Name	City	State
Netherlands	Radboud UMC	Nijmegen	Gelderland

Sponsors (1)

Lead Sponsor	Collaborator
Cees Tack

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Monocyte count	The amount of monocytes following 60 minutes of adrenaline infusion compared to baseline to asses the adrenaline effect on the inflammatory response.	Change from baseline compared to after 1 hour
Secondary	Leukocyte count	Measurement of the amount of leukocytes	Change from baseline at day 30, 60 and 180 minutes 1, day 3 and day 7 after adrenaline infusion
Secondary	Leukocyte phenotype	Measuring several phenotypes by using a pre-defined panel of interest with flow-cytometry ( e.g. NK-cells, granulocytes)	Change from baseline at day 30, 60 and 180 minutes 1, day 3 and day 7 after adrenaline infusion
Secondary	Pro-inflammatory proteins	Pro-inflammatory proteins using Olink Proteomics AB inflammation panel with 92 circulating inflammatory proteins ( e.g. EN-rage, FIT3L)	Change from baseline at day 30, 60 and 180 minutes 1, day 3 and day 7 after adrenaline infusion
Secondary	Inflammation plasma parameters	Inflammatory plasma protein using ELISA, ( e.g high sensitive-crp)	Change from baseline at 30, 60 and 180 minutes day 1, day 3 and day 7 after adrenaline infusion
Secondary	Atherogenic parameters	Atherogenic parameters using ELISA method including but not limited to, VCAM-1, ICAM-1, E-Selectin, P-selectin, PAI-1, Plasma Endothelin	Change from baseline at 30, 60 and 180 minutes day 1, day 3 and day 7 after adrenaline infusion
Secondary	Insulin	Plasma levels of insulin	Change from baseline at, 60 and 180 minutes
Secondary	Adrenaline	Plasma levels of adrenaline	Change from baseline at 30, 60 and 180 minutes
Secondary	Noradrenaline	Plasma levels of noradrenaline	Change from baseline at 30, 60 and 180 minutes
Secondary	Glucose variability	Glucose variability measured by the blinded continuous glucose monitor including but not limited to, measuring time within range, amount of hypoglycaemic events, amount of hyperglycaemic events.	2 weeks
Secondary	Ex vivo cytokines	Ex vivo production of pro- and anti-inflammatory cytokines and chemokines after ex vivo stimulation of isolated monocytes, including TNF-a, IL-6, IL-10 and IL-1ß.	Change from baseline at 30, 60 and 180 minutes, day 1, day 3 and day 7 after adrenaline infusion
Secondary	Distribution of monocyte subset	Distribution of pro- and anti-inflammatory monocyte subsets using FACS (Fluorescence-activated Cell Sorting)	Change from baseline at 30, 60 and 180 minutes, day 1, day 3 and day 7 after adrenaline infusion