To elucidate whether reducing glycemic variability with hybrid closed-loop therapy inhibits the inflammatory response (e.g. leukocyte phenotype, cytokine production, inflammatory proteins) in people with T1DM. Our secondary objectives are to…
ID
Source
Brief title
Condition
- Diabetic complications
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main endpoint is the difference in monocyte count between intervention and
control at the end of the study.
Secondary outcome
• Immunophenotyping of leukocytes and other blood cells
• Plasma levels of the following parameters:
o Cytokines (e.g. TNF-α, IL-6, IL-1β)
o Chemokines (e.g. MCP-1, IL-8)
o Atherogenic markers (e.g. VCAM-1, ICAM-1, E-selectin)
o Coagulation markers (e.g. Von Willebrand factor, factor VIII)
o hsCRP
• Proteomics on inflammatory markers measured by the Olink inflammation panel
• Production of pro- and anti-inflammatory cytokines following ex vivo
stimulation of leukocytes
• Functional changes in monocytes (e.g. endothelial migration and adhesion,
differentiation)
• Lipid profile (e.g. LDL, HDL, cholesterol, non-HDL, triglycerides)
• Gene expression changes in leukocytes
• Epigenetic changes in leukocytes
• Leukocyte metabolism
• ROS production in neutrophils
• Intracellular cytokine production of leukocytes
• Glycemic variability as determined by CV, glycemic variability percentage
(GVP) and other commonly used measures
• Urinary albumin/creatine ratio
• Markers of retinopathy as assessed with optical coherence tomography
angiography and optical coherence tomography
• Effect of reducing GV on patient reported outcomes
Background summary
People with type 1 diabetes mellitus (T1DM) are at high risk for cardiovascular
complications. Chronic low-grade inflammation of the arterial wall is an
important risk factor for atherosclerosis. We showed previously that
hyperglycemia in T1DM increases inflammation of the arterial wall, but observed
no differences based on average glucose values. Glycemic variability (GV)
reflects the difference between high and low glucose values and the frequency
of these changes. Interestingly, GV has independently been associated with
cardiovascular events. We think that this can partly be explained by the effect
of GV on systemic inflammation. Recent studies elucidated that variable glucose
values have a greater impact on inflammation in vitro than high but stable
glucose values. We hypothesize that reducing GV, through hybrid closed-loop
therapy, leads to a decrease in systemic inflammation in people with T1DM.
Study objective
To elucidate whether reducing glycemic variability with hybrid closed-loop
therapy inhibits the inflammatory response (e.g. leukocyte phenotype, cytokine
production, inflammatory proteins) in people with T1DM. Our secondary
objectives are to evaluate the effect of reducing GV on arterial wall
inflammation as reflected by circulating surrogate markers, and the effect of
improvements in GV on patient reported outcomes. We will also investigate
whether reducing GV decreases the progression of retinopathy and nephropathy.
Study design
Randomized controlled trial with a waitlist control design
Intervention
The intervention is a hybrid closed-loop system that consists of the CamAPS FX
algorithm, a mylife YpsoPump insulin pump and a Freestyle Libre 3 continuous
glucose monitoring sensor.
Study burden and risks
The hybrid closed-loop system that will be used in this trial is CE-certified
and brings minimal additional risks compared to conventional treatment for
T1DM. Participants in the intervention arm will have five visits in the
hospital. During these visits, a total of 160 mL blood, two ophthalmological
assessments, two urine collections, and two questionnaire sessions will
commence. The waitlist controls will have two additional visits, where 75 mL
blood, one ophthalmological assessment, and one urine collection are required
in addition to those during the intervention period.
Geert Grooteplein Zuid 10
Nijmegen 6525 GA
NL
Geert Grooteplein Zuid 10
Nijmegen 6525 GA
NL
Listed location countries
Age
Inclusion criteria
Diagnosis with T1DM >= 1 year prior to screening
High glucose variability (CV >= 36%) >= 4 weeks prior to screening
Age between 16 and 65 years
BMI between 18-30 kg/m^2
Average glucose between 4.4-11.1 mmol/L
Exclusion criteria
Current use of hybrid closed-loop therapy
Any event of cardiovascular disease in the past 5 years (e.g. myocardial
infarction, stroke, symptomatic peripheral arterial disease)
Pregnancy or planned pregancy
Diagnosis with auto-inflammatory or auto-immune disease
Occupations that include highly irregular working schedules (e.g. shift work)
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL87963.091.24 |