Role of Adrenaline in in the Inflammatory Response in Diabetes (RAID)

• ClinicalTrials.gov Identifier: NCT05990933
• Recruitment Status: Not yet recruiting
• First Posted: August 14, 2023
• Last Update Posted: August 14, 2023
• Sponsor: Cees Tack
• Information provided by (Responsible Party): Cees Tack, Radboud University Medical Center

Tracking Information

• First Submitted Date: August 2, 2023
• First Posted Date: August 14, 2023
• Last Update Posted Date: August 14, 2023
• Estimated Study Start Date: September 2023
• Estimated Primary Completion Date: October 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 10, 2023)

Monocyte count [ Time Frame: Change from baseline compared to after 1 hour ]

The amount of monocytes following 60 minutes of adrenaline infusion compared to baseline to asses the adrenaline effect on the inflammatory response.

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: August 10, 2023)

• Leukocyte count [ Time Frame: Change from baseline at day 30, 60 and 180 minutes 1, day 3 and day 7 after adrenaline infusion ]
  Measurement of the amount of leukocytes
• Leukocyte phenotype [ Time Frame: Change from baseline at day 30, 60 and 180 minutes 1, day 3 and day 7 after adrenaline infusion ]
  Measuring several phenotypes by using a pre-defined panel of interest with flow-cytometry ( e.g. NK-cells, granulocytes)
• Pro-inflammatory proteins [ Time Frame: Change from baseline at day 30, 60 and 180 minutes 1, day 3 and day 7 after adrenaline infusion ]
  Pro-inflammatory proteins using Olink Proteomics AB inflammation panel with 92 circulating inflammatory proteins ( e.g. EN-rage, FIT3L)
• Inflammation plasma parameters [ Time Frame: Change from baseline at 30, 60 and 180 minutes day 1, day 3 and day 7 after adrenaline infusion ]
  Inflammatory plasma protein using ELISA, ( e.g high sensitive-crp)
• Atherogenic parameters [ Time Frame: Change from baseline at 30, 60 and 180 minutes day 1, day 3 and day 7 after adrenaline infusion ]
  Atherogenic parameters using ELISA method including but not limited to, VCAM-1, ICAM-1, E-Selectin, P-selectin, PAI-1, Plasma Endothelin
• Insulin [ Time Frame: Change from baseline at, 60 and 180 minutes ]
  Plasma levels of insulin
• Adrenaline [ Time Frame: Change from baseline at 30, 60 and 180 minutes ]
  Plasma levels of adrenaline
• Noradrenaline [ Time Frame: Change from baseline at 30, 60 and 180 minutes ]
  Plasma levels of noradrenaline
• Glucose variability [ Time Frame: 2 weeks ]
  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.
• Ex vivo cytokines [ Time Frame: Change from baseline at 30, 60 and 180 minutes, day 1, day 3 and day 7 after adrenaline infusion ]
  Ex vivo production of pro- and anti-inflammatory cytokines and chemokines after ex vivo stimulation of isolated monocytes, including TNF-α, IL-6, IL-10 and IL-1β.
• Distribution of monocyte subset [ Time Frame: Change from baseline at 30, 60 and 180 minutes, day 1, day 3 and day 7 after adrenaline infusion ]
  Distribution of pro- and anti-inflammatory monocyte subsets using FACS (Fluorescence-activated Cell Sorting)

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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

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 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.

• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: Non-Randomized
Intervention Model: Single Group Assignment
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.

Masking: None (Open Label)
Primary Purpose: Basic Science

Condition

• Inflammatory Response
• Diabetes type1
• Hypoglycemia

Intervention

Drug: Adrenaline

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

Other Name: Adrenaline infusion

Study Arms

• Experimental: People with type 1 diabetes
  The participants with type 1 diabetes will receive an intravenous infusion of adrenaline at a rate of 0.04ug/kg/min for 1 hour.
  Intervention: Drug: Adrenaline
• Active Comparator: Healthy individuals
  The participants without type 1 diabetes will receive an intravenous infusion of adrenaline at a rate of 0.04ug/kg/min for 1 hour.
  Intervention: Drug: Adrenaline

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: August 10, 2023): 30
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: October 2024
• Estimated Primary Completion Date: October 2024 (Final data collection date for primary outcome measure)

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
• Overt impaired hypoglycaemic awareness assed by the Clarke Questionnaire 4 or higher

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 16 Years to 75 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Ilyas Mustafajev, MD; +31683358037; ilyas.mustafajev@radboudumc.nl

Contact: Rick Meijer, MD. PHD; rick.meijer@radboudumc.nl

• Listed Location Countries: Netherlands

Administrative Information

• NCT Number: NCT05990933
• Other Study ID Numbers: 114664
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: WE will share the study protocol using a data respository accesible through the research team on demand. Starting around 6 months after publication.
• Supporting Materials: Study Protocol
• Time Frame: 6 months after publication
• Access Criteria: The coordinating researcher will review acces requests. Seeing as the data are all anonimised acces will be granted for additional research in the field of inflammation or diabetes.

• Current Responsible Party: Cees Tack, Radboud University Medical Center
• Original Responsible Party: Same as current
• Current Study Sponsor: Cees Tack
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Cees Tack, MD. PHD.; Radboud University Medical Center (Radboudumc)

• PRS Account: Radboud University Medical Center
• Verification Date: August 2023