Discovering Early Biomarkers in Circulating Endothelial Cells for Diabetes Complications by Single Cell RNA Sequencing

NCT05169502 | Completed

• 2 other identifiers: 33579AUFF-NOVA Research Grant
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to discover early biomarkers in circulating endothelial cells for diabetes complications, by investigating circulating endothelial cells in blood samples from patients with newly diagnosed proliferative diabetic retinopathy, newly diagnosed maculopathy, patients with diabetes without eye diseases, and individuals without diabetes by single-cell RNA sequencing. The single-cell RNA sequencing analysis will make it possible to fully phenotype diabetes circulating endothelial cells at single-cell level and reveal the first atlas of circulating endothelial cells in humans at both healthy and diabetes conditions.

Conditions

Diabetes; Diabetes Mellitus; Proliferative Diabetic Retinopathy; Diabetic Maculopathy; Circulating Endothelial Cells

Outcome Measures

Primary Outcomes (1)

• Genome wide expression profile of circulating cells in blood samples from each cohort group

  Flow cytometry and single-cell RNA sequencing will be used to identify and consolidate potential biomarkers for diabetes complications, by making a genome wide expression profile used to characterise the different phenotypes of circulating cells in each cohort group.

  The PBMCs (including circulating endothelial cells) will be freshly isolated from the whole blood sampel, and frozen until all samples are collected (8 months). Afterwards flow cytometry and scRNA-seq analysis will be performed on all samples (2 months).

Study Arms (4)

Patients with diabetes and newly diagnosed proliferative diabetic retinopathy, level 4. (n=10)

Inclusion criteria: Type I or II diabetes, habile and age\>18 years. Exclusion criteria: Incapacitated or age\< 18 years. One 20mL blood sample from each patient will be analysed by flow cytometry and single cell RNA sequencing. A questionnaire describing the patients general health (gender, age, duration of diabetes, smoking status, blood pressure, BMI and hip/waist ratio) will be made.

Patients with diabetes and newly diagnosed diabetic maculopathy. (n=10)

These patients will be matched 1:1 to the patients with proliferative diabetic retinopathy, regarding gender, age, duration of diabetes, smoking status, and blood pressure. One 20mL blood sample from each patient will be analysed by flow cytometry and single cell RNA sequencing.A questionnaire describing the patients general health (gender, age, duration of diabetes, smoking status, blood pressure, BMI and hip/waist ratio) will be made.

Patients with diabetes without retinopathy, level 0. (n=10)

These patients will be matched 1:1 to the patients with proliferative diabetic retinopathy, regarding gender, age, duration of diabetes, smoking status, and blood pressure. One 20mL blood sample from each patient will be analysed by flow cytometry and single cell RNA sequencing.A questionnaire describing the patients general health (gender, age, duration of diabetes, smoking status, blood pressure, BMI and hip/waist ratio) will be made.

Individuals without diabetes and known eye diseases (n=10)

These patients will be matched 1:1 to the patients with proliferative diabetic retinopathy, regarding gender, age, smoking status, and blood pressure. One 20mL blood sample from each patient will be analysed by flow cytometry and single cell RNA sequencing.A questionnaire describing the patients general health (gender, age, smoking status, blood pressure, BMI and hip/waist ratio) will be made.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

The patients with newly diagnosed proliferative diabetic retinopathy and patients with newly diagnosed diabetic maculopathy will be recruited at department of Ophthalmology at Aarhus University Hospital. The healthy individuals and patients with diabetes and without eye diseases will be recruited at Steno Diabetes Center Aarhus, Aarhus University Hospital.

You may qualify if:

• Type I or II diabetes
• Habile
• Age\> 18 years

You may not qualify if:

• Incapacitated
• Age \< 18 years

Sponsors & Collaborators

• Aarhus University Hospital: lead
• University of Aarhus: collaborator

Study Sites (1)

Steno Diabetes Center Aarhus, Aarhus University Hospiral

Aarhus, 8000, Denmark

Location

Related Publications (4)

• Rajendran P, Rengarajan T, Thangavel J, Nishigaki Y, Sakthisekaran D, Sethi G, Nishigaki I. The vascular endothelium and human diseases. Int J Biol Sci. 2013 Nov 9;9(10):1057-69. doi: 10.7150/ijbs.7502. eCollection 2013.

  PMID: 24250251 BACKGROUND

• Carmeliet P. Angiogenesis in health and disease. Nat Med. 2003 Jun;9(6):653-60. doi: 10.1038/nm0603-653.

  PMID: 12778163 BACKGROUND

• Damani S, Bacconi A, Libiger O, Chourasia AH, Serry R, Gollapudi R, Goldberg R, Rapeport K, Haaser S, Topol S, Knowlton S, Bethel K, Kuhn P, Wood M, Carragher B, Schork NJ, Jiang J, Rao C, Connelly M, Fowler VM, Topol EJ. Characterization of circulating endothelial cells in acute myocardial infarction. Sci Transl Med. 2012 Mar 21;4(126):126ra33. doi: 10.1126/scitranslmed.3003451.

  PMID: 22440735 BACKGROUND

• Aird WC. Endothelial cell heterogeneity. Cold Spring Harb Perspect Med. 2012 Jan;2(1):a006429. doi: 10.1101/cshperspect.a006429.

  PMID: 22315715 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

A 20mL whole blood sample will be collected from each participant, which will be used to isolate the peripheral blood mononuclear cells (PBMCs).

MeSH Terms

Conditions

Diabetes Mellitus

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Niels Jessen, Professor

  Steno Diabetes Center Aarhus, Aarhus Universitet Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 1 Day
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: master of science, phd student at Department of Biomedicine

Study Record Dates

• First Submitted: November 24, 2021
• First Posted: December 27, 2021
• Study Start: December 8, 2021
• Primary Completion: August 1, 2024
• Study Completion: August 12, 2024
• Last Updated: August 20, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: The data will become available in 2024
• Access Criteria: Open acces atlas

Locations

DK (1)