Changes in the Retinal and Carotid Microcirculation After Restoring Normoglycemia in Patients With Type 2 Diabetes (OCTAUS-T2D)

Changes in the Retinal and Carotid Microcirculation After Restoring Normoglycemia in Patients With Type 2 Diabetes (OCTAUS-T2D Study)

This is a prospective and observational study in patients with type two diabetes. The study hypothesis is that chronic hyperglycemia causes an increase in the microcirculation on the carotid artery wall and retina, evaluated by angio-OCT. Furthermore, the reestablishment of normoglycemia would decrease this microcirculation, which could trigger hypoxic and ischemic changes, accelerating preclinical atherosclerosis. The study goal is to describe the microangiopathy in both territories in patients with type two diabetes and chronic hyperglycemia, and to evaluate changes after the reestablishment of normoglycemia.

Study Overview

• Status: Unknown
• Conditions: Arteriosclerosis; Type 2 Diabetes Mellitus; Diabetic Retinopathy; Carotid Atherosclerosis; Microangiopathy
• Intervention / Treatment: Drug: Antidiabetic treatment by usual care

Detailed Description

This is a prospective and observational study in patients with type two diabetes. The study hypothesis is that chronic hyperglycemia causes an increase in the microcirculation on the carotid artery wall (evaluating vasa vasorum by contrast-assessed carotid ultrasound) and retina (evaluated by angio-OCT). Furthermore, the reestablishment of normoglycemia would decrease this microcirculation, which could trigger hypoxic and ischemic changes, accelerating preclinical atherosclerosis. The primary outcome is to describe the microangiopathy in both territories in 20 patients with type two diabetes and chronic hyperglycemia (basal), and to evaluate the changes after the reestablishment of normoglycemia (at 1, 3 and 6 months). Additionally, clinical, laboratory, diet and biomarkers will be evaluated.

• Study Type: Observational
• Enrollment (Anticipated): 20

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08036
    • Recruiting
    • Hospital Clínic de Barcelona
    • Contact: Emilio Ortega, MD, PhD; Phone Number: +34932279846; Email: eortega1@clinic.ub.es
    • Sub-Investigator: Antonio J Amor, MD
    • Sub-Investigator: Marc Figueras, MD
    • Sub-Investigator: Rosa Gilabert, MD, PhD
    • Sub-Investigator: Montserrat Cofán, PhD
    • Sub-Investigator: Laura Boswell, MD
    • Sub-Investigator: Mireia Hereu
    • Sub-Investigator: Aleix Sala-Vila, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with type two diabetes with chronic hyperglycemia (HbA1c >9%) in who a swift and maintained improvement in glycemic control is expected, as a consequence of the antidiabetic treatment decided by usual care owing to the clinical situation. Patients with new diagnose of type two diabetes who start treatment (insulin and non-insulin drugs) in which a long-evolution diabetes is suspected will also be candidates.

Description

Inclusion Criteria:

1. Patients with type two diabetes with chronic hyperglycemia (HbA1c >9%) in who a swift and maintained improvement in glycemic control is expected, as a consequence of the antidiabetic treatment decided by usual care owing to the clinical situation.

   This treatment will include, in many cases, albeit not always, insulin (basal, basal-plus, mixes, or multiple doses). The usual clinical scenario will be failure to non-insulin antidiabetic drugs or to combined treatment (basal insulin and non-insulin drugs). Patients with new diagnose of type two diabetes who start treatment (insulin and non-insulin drugs) in which a long-evolution diabetes is suspected will also be candidates.

2. Caucasian and age between 35 and 75 years.
3. Informed consent by the patient or legal tutor.

Exclusion Criteria:

1. Previous history of carotid territory interventionism (stent o endarterectomy).
2. Presence of carotid plaques in the first centimetre of the posterior wall of the common carotid artery.
3. Ophtalmologic: Proliferative diabetic retinopathy and/or diabetic macular oedema, retinal photocoagulation, intravitreous therapy and/or vitreo-retinal surgery, myopia of >6 diopters, history of non-diabetic vascular retinopathy.
4. Stage 4 chronic kidney disease (estimated glomerular filtration <30 ml/min/1,73m2), organ transplant, HIV chronic infection, active tuberculosis, active malaria, chronic b or C hepatitis, cirrhosis or intestinal inflammatory disease.
5. Current pregnancy or breastfeeding, o gestational desire in the following two years.
6. History of alcohol or drug dependence (except for caffeine and nicotine) in the former 5 years, active depression or psychiatric disease, dementia, presence of another chronic or debilitating disease with short life-expectancy, institutionalization or severe disability.
7. Presence of contraindications for the use of ecographic contrast.
8. Current Participation in another study protocol.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in retinal microcirculation (perifoveal vessel density)	Changes in perifoveal vessel density, OCTA images will be processed to obtain vascular density measurements in this area (mm-1)	0, 1, 3 and 6 months
Changes in arterial wall microcirculation (vasa-vasorum density)	Changes vasa-vasorum (VV) density, VV signal as the ratio of the contrast agent signal of the VV and that of the lumen of the artery	0, 3 and 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in retinal microcirculation (Parafoveal vessel density )	OCTA images will be processed to obtain vascular density measurements in this area (mm-1)	0, 1, 3 and 6 months
Changes in retinal microcirculation (Total Avascular Area )	OCTA images will be processed to obtain total avascular area measurements (mm2)	0, 1, 3 and 6 months
Changes in retinal microcirculation (Foveal Avascular Area)	OCTA images will be processed to obtain foveal avascular zone area measurements (mm2)	0, 1, 3 and 6 months

Collaborators and Investigators

• Sponsor: Hospital Clinic of Barcelona
• Collaborators: Instituto de Salud Carlos III; Institut d'Investigacions Biomèdiques August Pi i Sunyer
• Investigators: Principal Investigator: Emilio Ortega, MD; PhD, Hospital Clinic of Barcelona

Publications and helpful links

General Publications

• Action to Control Cardiovascular Risk in Diabetes Study Group, Gerstein HC, Miller ME, Byington RP, Goff DC Jr, Bigger JT, Buse JB, Cushman WC, Genuth S, Ismail-Beigi F, Grimm RH Jr, Probstfield JL, Simons-Morton DG, Friedewald WT. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008 Jun 12;358(24):2545-59. doi: 10.1056/NEJMoa0802743. Epub 2008 Jun 6.
• Sanahuja J, Alonso N, Diez J, Ortega E, Rubinat E, Traveset A, Alcubierre N, Betriu A, Castelblanco E, Hernandez M, Purroy F, Arcidiacono MV, Jurjo C, Fernandez E, Puig-Domingo M, Groop PH, Mauricio D. Increased Burden of Cerebral Small Vessel Disease in Patients With Type 2 Diabetes and Retinopathy. Diabetes Care. 2016 Sep;39(9):1614-20. doi: 10.2337/dc15-2671. Epub 2016 Jun 8.
• Arcidiacono MV, Rubinat E, Borras M, Betriu A, Trujillano J, Vidal T, Mauricio D, Fernandez E. Left carotid adventitial vasa vasorum signal correlates directly with age and with left carotid intima-media thickness in individuals without atheromatous risk factors. Cardiovasc Ultrasound. 2015 Apr 17;13:20. doi: 10.1186/s12947-015-0014-7.
• Catalan M, Herreras Z, Pinyol M, Sala-Vila A, Amor AJ, de Groot E, Gilabert R, Ros E, Ortega E. Prevalence by sex of preclinical carotid atherosclerosis in newly diagnosed type 2 diabetes. Nutr Metab Cardiovasc Dis. 2015 Aug;25(8):742-8. doi: 10.1016/j.numecd.2015.04.009. Epub 2015 May 7.
• Dimitrova G, Chihara E, Takahashi H, Amano H, Okazaki K. Author Response: Quantitative Retinal Optical Coherence Tomography Angiography in Patients With Diabetes Without Diabetic Retinopathy. Invest Ophthalmol Vis Sci. 2017 Mar 1;58(3):1767. doi: 10.1167/iovs.17-21706. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): January 2, 2018
• Primary Completion (Anticipated): January 1, 2020
• Study Completion (Anticipated): January 1, 2020

Study Registration Dates

• First Submitted: May 10, 2018
• First Submitted That Met QC Criteria: July 13, 2018
• First Posted (Actual): July 20, 2018

Study Record Updates

• Last Update Posted (Actual): July 24, 2018
• Last Update Submitted That Met QC Criteria: July 20, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arterial Occlusive Diseases; Eye Diseases; Endocrine System Diseases; Diabetic Angiopathies; Diabetes Complications; Retinal Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Arteriosclerosis; Carotid Artery Diseases; Atherosclerosis; Physiological Effects of Drugs; Hypoglycemic Agents
• Other Study ID Numbers: PI 17/01479

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No