Condition category
Nutritional, Metabolic, Endocrine
Date applied
26/09/2018
Date assigned
04/10/2018
Last edited
04/10/2018
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
The retina, found in the back of the eye, is responsible for vision, by transforming a light stimulus in an electrical one that can be interpreted by our brain. The retina needs a rich blood supply and its effective autoregulation is key to its normal function. In diabetes mellitus (DM), there is some evidence of an early impairment of the vessel autoregulation, which inflammation may contribute to. With a novel non-invasive imaging device (OCT-Angiography) we are able to visualize the retina microvasculature (small blood vessels around the retina) and study its response to external stimuli. In this study, we will compare the response of retinal vessels between healthy individuals and the ones with type 1 diabetes.

Who can participate?
Patients with type 1 diabetes mellitus with no eye involvement, and a similar sample of healthy subjects

What does the study involve?
The participants will be subjected to test that cause a dilation or constriction of the retinal vessels, and the response compared between the two groups.

Participants will be asked to complete two tests (hypoxia challenge test and handgrip test), which cause a dilation or constriction of the blood vessels in the retina. The responses to both tests will be monitored using an imaging device and the results will be compared between both groups. Tear and blood samples will be taken from both groups. This will take around two hours and only one study visit will be required from all participants.

What are the possible benefits and risks of participating?
All participants will benefit with a comprehensive ophthalmological examination and counselling. In case of any abnormality, possibility of medical follow-up will be offered. The tests performed are safe and standardised for clincal research. There are no known risks to participants taking part in this study.

Where is the study run from?
Hospital de Santa Maria, Lisbon (Portugal)

When is the study starting and how long is it expected to run for?
February 2018 to November 2019

Who is funding the study?
1. AstraZeneca (UK)
2. Faculty of Medicine of the University of Lisbon (Portugal)

Who is the main contact?
Dr. David Sousa
davidsousa@medicina.ulisboa.pt

Trial website

Contact information

Type

Scientific

Primary contact

Dr David Cordeiro Sousa

ORCID ID

http://orcid.org/0000-0002-7680-0325

Contact details

Hospital Santa Maria - Oftalmologia
Av Prof Egas Moniz
Lisboa
1649-035
Portugal

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

469/17

Study information

Scientific title

Retinal Vascular Function Analysis using Optical Coherence Tomography Angiography

Acronym

RV_OCTA

Study hypothesis

Aim 1: To describe the effects of hypoxia in ocular hemodynamics using OCT-A.
Hypothesis 1: A reduced inspired fraction of oxygen induces a detectable retinal vascular response – i.e. vasodilation.

Aim 2: To compare the retinal vessel density between T1D patients without DR and a cohort of age and gender-matched healthy individuals.
Hypotheses:
2.1. The retinal vessel density in diabetic patients with no evidence of DR on fundus examination is significantly lower than in healthy subjects.
2.2. The retinal vessel density in diabetic patients with no evidence of DR is related with duration of disease and/or HbA1c.

Aim 3: To describe the retinal vascular response to HCT in T1D patients without DR, in comparison with age and gender-matched healthy individuals.
Hypotheses:
3.1. The retinal vascular response of T1D patients without DR in response to a hypoxic stress is different than the physiologic vasodilation observed in healthy individuals.
3.2. here is a relationship between the duration of disease and/or HbA1c and retinal vascular response to hypoxia.

Aim 4: To describe the retinal vascular response to isometric handgrip test in T1D patients without DR, in comparison with age and gender-matched healthy individuals.
Hypotheses:
4.1. The retinal vascular response of T1D patients without DR in response to isometric exercise is different than the physiologic vasoconstriction observed in healthy individuals.
4.2. There is a relationship between the duration of disease and/or HbA1c and retinal vascular response to handgrip test.

Aim 5: To compare inflammatory cytokines (IL-1β and TNF) concentration in tears and in circulation between T1D patients without DR and a cohort of age and gender-matched healthy individuals.
Hypotheses:
5.1. Inflammation biomarkers are increased in T1D patients even with no evidence of DR, when compared to healthy subjects.
5.2. There is a relationship between inflammation biomarkers concentration and retinal vascular response to HCT/handgrip test.
5.3. There is a relationship between the duration of disease and/or HbA1c and inflammatory cytokines’ concentration.

Ethics approval

Lisbon Academic Medical Center (CAML), 06/03/2018, Ref. 469/17

Study design

Interventional non-randomised controlled study

Primary study design

Interventional

Secondary study design

Non randomised study

Trial setting

Hospitals

Trial type

Diagnostic

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet

Condition

Type 1 diabetes mellitus without diabetic retinopathy

Intervention

This study will involve type 1 diabetes (T1D) patients without diabetic retinopahty (DR), and a demographically similar control group. Both groups will be subjected to two standardized tests:
1. Hypoxia Challenge Test
2. Handgrip Test
Both tests are expected to induce a physiologic retinal vascular response, with vasodilation in the former and vasoconstriction in the latter. OCT-Angiography will be performed before and during each test to comparatively characterise retinal microvasculature response and its detailed anatomy. Tears and venous blood samples will be collected from all subjects, and IL-1β and TNF concentrations will be measured to investigate if these are associated with a different vascular response pattern between groups. The total duration of the protocol is expected to be approximately 2 hours per patient, and a single visit is needed as all measurements will be performed during that visit.

Intervention type

Behavioural

Phase

Drug names

Primary outcome measure

To assess aims 1, 3, 4 and 5:
1. Macular vessel density, assessed using ocular coherence tomography angiography built-in software after the HCT test at the single study visit
2. Peripapillary vessel density, assessed using ocular coherence tomography angiography built-in software after the handgrip test at the single study visit

To assess aim 2:
1. Macular vessel density, assessed using ocular coherence tomography angiography built-in software at the single study visit
2. Peripapillary vessel density, assessed using ocular coherence tomography angiography built-in software at the single study visit

To assess aim 5:
1. Inflammatory cytokine (TNF and IL-1β) concentration in tear and blood samples, assessed using ELISA at the single study visit


Secondary outcome measures

To assess all aims:
1. Metabolic data regarding diabetic disease:
1.1. HbA1c values, assessed using a standard laboratory test with a blood sample at the single study visit
1.2. Length of disease, assessed using a chart review of the patient at the single study visit

To assess aims 1, 3, 4 and 5:
1. Changes in cardiorespiratory parameters in relation to macular and peripapillary vessel density change:
1.1. Heart rate, assessed using a polygraph and an oximeter from a single finger throughout the single study visit
1.2. Electrocardiography RR-interval variability, assessed using polygraph and an oximeter from a single finger during the HCT test at the single study visit
1.3. Arterial pressure, assessed using a polygraph and an oximeter from a single finger throughout the single study visit
1.4. Oxygen desaturation index, assessed using polygraph and an oximeter from a single finger during the HCT test at the single study visit
1.5. Respiratory rate, assessed using a polygraph with a respiratory band during the HCT test at the single study visit

To assess aims 2 and 5:
1. Inflammatory cytokine (TNF and IL-1β) concentration in tear and blood samples, assessed using ELISA at the baseline

Overall trial start date

01/02/2018

Overall trial end date

30/11/2019

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Aged 18 years or older
2. Healthy
3. Type 1 diabetes

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

27 diabetic patients and 27 controls

Participant exclusion criteria

1. Presence of significant lens opacities (Lens Opacities Classification System III stage 2 or more)
2. High refractive error (spherical equivalent below -6.50 or above +4.00 diopters)
3. History of glaucoma or ocular hypertension
4. Neuro-ophthalmic disease
5. Previous intraocular surgery
6. Untreated hypertension (systolic blood pressure >140 mmHg and diastolic blood pressure >90 mmHg)
7. Treated hypertension
8. Nephropathy
9. Other documented microvascular complication
10. Local or systemic inflammatory diseases
11. Taking vasoactive drugs
12. Smokers of more than 20 cigarettes per day
13. Pregnancy (urine pregnancy test performed if deemed necessary)
Subjects will be asked to abstain from alcohol and caffeine for at least 6 hours before the study to reduce the possible autonomic effects and measurement bias.

Recruitment start date

20/10/2018

Recruitment end date

30/11/2018

Locations

Countries of recruitment

Portugal

Trial participating centre

Hospital Santa Maria
Av Prof Egas Moniz
Lisboa
1649-035
Portugal

Sponsor information

Organisation

Centro de Estudos Ciências da Visão - FMUL

Sponsor details

Av Prof Egas Moniz
Lisboa
1649-028
Portugal

Sponsor type

University/education

Website

Funders

Funder type

Not defined

Funder name

Bolsa de Investigação Fundação AstraZeneca / Faculdade de Medicina da Universidade de Lisboa

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Planned publication in a peer-reviewed medline-indexed journal in 2019/2020

IPD sharing statement:
The data sharing plans for the current study are unknown and will be made available at a later date

Intention to publish date

20/12/2019

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

2018 results in https://www.ncbi.nlm.nih.gov/pubmed/29160042

Publication citations

Additional files

Editorial Notes