Clinical trial NCT03594591: Changes in the Retinal and Carotid Microcirculation After Restoring Normoglycemia in Patients With Type 2 Diabetes
Official title: Changes in the Retinal and Carotid Microcirculation After Restoring Normoglycemia in Patients With Type 2 Diabetes (OCTAUS-T2D Study)
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Type 2 Diabetes Mellitus
Microangiopathy
Diabetic Retinopathy
Arteriosclerosis
Carotid Atherosclerosis
Lead sponsor: Hospital Clinic of Barcelona
Sponsor class: OTHER
Collaborators: name: Instituto de Salud Carlos III
name: Institut d'Investigacions Biomèdiques August Pi i Sunyer
First posted: 2018-07-20
Enrollment: 20
Sex: ALL
Minimum age (years): 35
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Changes in retinal microcirculation (perifoveal vessel density)
timeFrame: 0, 1, 3 and 6 months
measure: Changes in arterial wall microcirculation (vasa-vasorum density)
timeFrame: 0, 3 and 6 months
Secondary outcomes:
measure: Changes in retinal microcirculation (Parafoveal vessel density )
timeFrame: 0, 1, 3 and 6 months
measure: Changes in retinal microcirculation (Total Avascular Area )
timeFrame: 0, 1, 3 and 6 months
measure: Changes in retinal microcirculation (Foveal Avascular Area)
timeFrame: 0, 1, 3 and 6 months
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
Study officials:
affiliation: Hospital Clínic of Barcelona
name: Emilio Ortega, MD; PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
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.
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. No abstract available.