Changes in the Retinal and Carotid Microcirculation After Restoring Normoglycemia in Patients With Type 2 Diabetes

Type 2 Diabetes Mellitus Clinical Trial

— OCTAUS-T2D  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03594591
• Other study ID #: PI 17/01479
• Status: Recruiting
• Start date: January 2, 2018
• Est. completion date: January 1, 2020

Study information

• Verified date: July 2018
• Source: Hospital Clinic of Barcelona
• Contact: Emilio Ortega, MD, PhD
• Phone: +34932279846
• Email: eortega1[@]clinic.ub.es
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: January 1, 2020
• Est. primary completion date: January 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 35 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Arteriosclerosis
• Atherosclerosis
• Carotid Artery Diseases
• Carotid Atherosclerosis
• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Diabetic Retinopathy
• Microangiopathy
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Antidiabetic treatment by usual care
Observation of changes in the microcirculation after optimization of antidiabetic therapy by usual care.

Locations

Country	Name	City	State
Spain	Hospital Clínic de Barcelona	Barcelona

Sponsors (3)

Lead Sponsor	Collaborator
Hospital Clinic of Barcelona	Institut d'Investigacions Biomèdiques August Pi i Sunyer, Instituto de Salud Carlos III

Country where clinical trial is conducted

Spain, 

References & Publications (5)

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. — View Citation

Arcidiacono MV, Rubinat E, Borras M, Betriu A, Trujillano J, Vidal T, Mauricio D, Fernández 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. — View Citation

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. — View Citation

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. — View Citation

Sanahuja J, Alonso N, Diez J, Ortega E, Rubinat E, Traveset A, Alcubierre N, Betriu À, Castelblanco E, Hernández M, Purroy F, Arcidiacono MV, Jurjo C, Fernández 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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