Clinical trial NCT05944640: Dynamic Parameters of Glucose Control in Relation to Biomarkers in Serum and Intraocular Fluid in Patients With Diabetes
Official title: Dynamic Parameters of Glucose Control in Relation to Biomarkers in Serum and Intraocular Fluid in Diabetic Patients With Ocular Complications
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Diabetes Complications
Keywords: biomarkers
retinopathy
miRNA
diabetes mellitus
glucose variability
Lead sponsor: Charles University, Czech Republic
Sponsor class: OTHER
Collaborators: name: Czech Health Research Council
First posted: 2023-07-13
Enrollment: 213
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult patients with T1DM or T2DM treated with insulin with or without any form of diabetic retinopathy and the matched controls, who are indicated to ocular surgery procedure as standard of care.

Brief summary: Our project investigates the new characteristics of diabetic retinopathy using liquid eye biopsy in combination with novel parameters of glucose control obtained with continuous glucose monitoring. This approach will bring new knowledge and implications for future therapies.

Detailed description: Diabetic retinopathy is one of the most common causes of blindness in developed countries. The short-term glucose fluctuations have been suggested as a factor contributing to the risk of diabetic complications including ocular complications. We hypothesize that modulatory and other biological abilities of miRNAs and inflammatory chemokines/cytokines have a significant impact on the development and the progression of diabetic retinopathy. Our main goal is to identify the biomarkers that will in time be used for new screening, diagnostic, and treatment strategies for patients with diabetic retinopathy, bring a better prevention and early treatment to them and thus improve their quality of life while saving the cost associated with advanced forms of retinopathy.

Eligibility criteria: Inclusion Criteria:

* type 1 or type 2 diabetes
* ≥ 18 years old
* treatment with insulin for at least 5 years prior baseline
* any form of diabetic retinopathy and macular edema
* HbA1c \< 10%
* written informed consent prior to starting study related activity

Exclusion Criteria:

* any active intraocular or periocular infectious or non-infectious inflammation in study eye
* uncontrolled glaucoma
* history of intraocular inflammation or trauma in study eye
* intravitreal anti-VEGF therapy in study eye during a 3-month perido prior to baseline
* use of corticosteroid intravitreal implant in study eye at any time

Primary outcomes:
measure: miRNA
timeFrame: Year 2025
measure: TIR
timeFrame: Year 2025
Secondary outcomes:
measure: miRNA expression differences
timeFrame: Year 2025
measure: Glycemic variability
timeFrame: Year 2025
measure: Mean sensor glucose concentration
timeFrame: Year 2025
Other outcomes:
Locations:
city: Prague
country: Czechia
facility: General University Hospital in Prague
Study officials:
affiliation: Charles University and General University Hospital in Prague
name: Martin Prázný, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ceriello A, Esposito K, Piconi L, Ihnat MA, Thorpe JE, Testa R, Boemi M, Giugliano D. Oscillating glucose is more deleterious to endothelial function and oxidative stress than mean glucose in normal and type 2 diabetic patients. Diabetes. 2008 May;57(5):1349-54. doi: 10.2337/db08-0063. Epub 2008 Feb 25.
citation: Soupal J, Skrha J Jr, Fajmon M, Horova E, Mraz M, Skrha J, Prazny M. Glycemic variability is higher in type 1 diabetes patients with microvascular complications irrespective of glycemic control. Diabetes Technol Ther. 2014 Apr;16(4):198-203. doi: 10.1089/dia.2013.0205. Epub 2014 Jan 8.
citation: Zoppini G, Verlato G, Targher G, Casati S, Gusson E, Biasi V, Perrone F, Bonora E, Muggeo M. Is fasting glucose variability a risk factor for retinopathy in people with type 2 diabetes? Nutr Metab Cardiovasc Dis. 2009 Jun;19(5):334-9. doi: 10.1016/j.numecd.2008.02.007. Epub 2008 Jun 20.
citation: Takao T, Ide T, Yanagisawa H, Kikuchi M, Kawazu S, Matsuyama Y. The effects of fasting plasma glucose variability and time-dependent glycemic control on the long-term risk of retinopathy in type 2 diabetic patients. Diabetes Res Clin Pract. 2011 Feb;91(2):e40-2. doi: 10.1016/j.diabres.2010.10.009. Epub 2010 Oct 29.
citation: Vujosevic S, Aldington SJ, Silva P, Hernandez C, Scanlon P, Peto T, Simo R. Screening for diabetic retinopathy: new perspectives and challenges. Lancet Diabetes Endocrinol. 2020 Apr;8(4):337-347. doi: 10.1016/S2213-8587(19)30411-5. Epub 2020 Feb 27.
citation: Meister G, Landthaler M, Dorsett Y, Tuschl T. Sequence-specific inhibition of microRNA- and siRNA-induced RNA silencing. RNA. 2004 Mar;10(3):544-50. doi: 10.1261/rna.5235104.
citation: Martinez B, Peplow PV. MicroRNAs as biomarkers of diabetic retinopathy and disease progression. Neural Regen Res. 2019 Nov;14(11):1858-1869. doi: 10.4103/1673-5374.259602.
citation: Boss JD, Singh PK, Pandya HK, Tosi J, Kim C, Tewari A, Juzych MS, Abrams GW, Kumar A. Assessment of Neurotrophins and Inflammatory Mediators in Vitreous of Patients With Diabetic Retinopathy. Invest Ophthalmol Vis Sci. 2017 Oct 1;58(12):5594-5603. doi: 10.1167/iovs.17-21973.
citation: Wu H, Hwang DK, Song X, Tao Y. Association between Aqueous Cytokines and Diabetic Retinopathy Stage. J Ophthalmol. 2017;2017:9402198. doi: 10.1155/2017/9402198. Epub 2017 Jun 7.
citation: Mastropasqua R, D'Aloisio R, Di Nicola M, Di Martino G, Lamolinara A, Di Antonio L, Tognetto D, Toto L. Relationship between aqueous humor cytokine level changes and retinal vascular changes after intravitreal aflibercept for diabetic macular edema. Sci Rep. 2018 Nov 8;8(1):16548. doi: 10.1038/s41598-018-35036-9.