Clinical trial NCT05990933: Role of Adrenaline in in the Inflammatory Response in Diabetes
Official title: Role of Adrenaline in the Inflammatory Response in People with Diabetes Mellitus Type 1, and Healthy Individuals
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Inflammatory Response
Diabetes Type1
Hypoglycemia
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
First posted: 2023-08-14
Enrollment: 30
Sex: ALL
Minimum age (years): 16
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: 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 and a week after start of infusion. These 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.
Primary purpose: BASIC_SCIENCE

Brief 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.

Detailed description: Objective: The aim of the present study is to study the effect of increased adrenaline levels on the inflammatory response (e.g. leukocyte phenotype, cytokines, inflammatory proteins) by administering exogenous adrenaline in participants with type 1 diabetes and healthy participants.

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. We 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.

Eligibility criteria: 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

Primary outcomes:
measure: Monocyte count
timeFrame: Change from baseline compared to after 1 hour
Secondary outcomes:
measure: Leukocyte count
timeFrame: Change from baseline at day 30, 60 and 180 minutes 1, day 3 and day 7 after adrenaline infusion
measure: Leukocyte phenotype
timeFrame: Change from baseline at day 30, 60 and 180 minutes 1, day 3 and day 7 after adrenaline infusion
measure: Pro-inflammatory proteins
timeFrame: Change from baseline at day 30, 60 and 180 minutes 1, day 3 and day 7 after adrenaline infusion
measure: Inflammation plasma parameters
timeFrame: Change from baseline at 30, 60 and 180 minutes day 1, day 3 and day 7 after adrenaline infusion
measure: Atherogenic parameters
timeFrame: Change from baseline at 30, 60 and 180 minutes day 1, day 3 and day 7 after adrenaline infusion
measure: Insulin
timeFrame: Change from baseline at, 60 and 180 minutes
measure: Adrenaline
timeFrame: Change from baseline at 30, 60 and 180 minutes
measure: Noradrenaline
timeFrame: Change from baseline at 30, 60 and 180 minutes
measure: Glucose variability
timeFrame: 2 weeks
measure: Ex vivo cytokines
timeFrame: Change from baseline at 30, 60 and 180 minutes, day 1, day 3 and day 7 after adrenaline infusion
measure: Distribution of monocyte subset
timeFrame: Change from baseline at 30, 60 and 180 minutes, day 1, day 3 and day 7 after adrenaline infusion
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboud UMC
state: Gelderland
Study officials:
affiliation: Radboud University Medical Center (Radboudumc)
name: Cees Tack, MD. PHD.
role: PRINCIPAL_INVESTIGATOR
References: