Condition category
Eye Diseases
Date applied
18/10/2018
Date assigned
23/10/2018
Last edited
23/10/2018
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
At present, diabetic retinopathy, a serious complication of diabetes affecting the eye, is diagnosed and graded in severity by taking photographs of the retina at the back of the eye. In the UK people with diabetes are screened for diabetic retinopathy on an annual basis, costing about £50 per patient per year in England and Wales. While retinal screening is quite accurate in detecting diabetic retinopathy and discriminating between the sight threatening forms, this screening is cost prohibitive as a large-scale screening measure in low and medium income countries where the prevalence of diabetes may be as high as 20%. Other than diabetic retinopathy retinal screening there is currently no other rapid cost-effective means for providing routine screening of sight threatening diabetic retinopathy, which is the most common form of blindness in the working age. The most consistent risk factors for the development of diabetic retinopathy are long duration of diabetes, hyperglycaemia (high blood sugar) and hypertension (high blood pressure). However, there is substantial variation in the onset and severity of diabetic retinopathy that cannot be fully explained by hyperglycaemia and hypertension, suggesting that other risk factors have a role. The aim of this study is to measure existing biological molecules (biomarkers) found in the blood of people with diabetes that may identify people at risk of diabetic retinopathy with or without other diabetic complications. The development of a blood test would provide a rapid cost-effective, time-effective and patient friendly means of screening for sight threatening diabetic retinopathy at the population level, broadening access to care globally. Such a blood test would provide an initial screening tool that then could be confirmed with retinal imaging.

Who can participate?
Healthy volunteers and patients with diabetes aged over 40 with varying severity of diabetic retinopathy

What does the study involve?
The study involves a single visit to either of the centres where information is collected including height, weight, waist and hip and blood pressure measurements. All participants have about 20 ml of blood taken. The people with varying severity of diabetic retinopathy undergo retinal imaging and an OCT scan.

What are the possible benefits and risks of participating?
There are no immediate benefits but the results will help with the development of new diagnostics. During blood collection, the participants may experience mild pain of the needle pricking the skin and rarely bruising may occur.

Where is the study run from?
1. Moorfields Eye Hospital NHS Foundation Trust (UK)
2. Hillingdon Hospitals NHS Foundation Trust (UK)

When is the study starting and how long is it expected to run for?
October 2017 to December 2021

Who is funding the study?
Global Challenges Research Fund and the UK Research Innovation (MRC)

Who is the main contact?
Prof. Sobha Sivaprasad
sobha.sivaprasad@nhs.net

Trial website

Contact information

Type

Scientific

Primary contact

Prof Sobha Sivaprasad

ORCID ID

Contact details

Moorfields Eye Hospital
London
EC1V 2PD
United Kingdom
+44 (0)7817886759
sobha.sivaprasad@nhs.net

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

SIVS1046

Study information

Scientific title

Prospective multicentre discovery and validation of diagnostic circulating biomarkers to detect sight-threatening diabetic retinopathy

Acronym

Biomarker Study

Study hypothesis

The aim is to identify circulating biomarkers with the hope of developing a sensor that can be used to identify people at risk of sight threatening diabetic retinopathy with or without other diabetic complications by doing a simple blood test.

Ethics approval

South Central - Oxford B Research Ethics Committee, 04/09/2018, ref: 18/SC/0477

Study design

Prospective multicentre case control study

Primary study design

Observational

Secondary study design

Case-control study

Trial setting

Hospitals

Trial type

Diagnostic

Patient information sheet

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

Condition

Diabetic retinopathy

Intervention

Participant demographics and baseline characteristics will be captured as well as height, weight, waist and hip measurements and blood pressure. Retinal imaging and OCT scans will be performed on patients with varying degrees of diabetic retinopathy but not on healthy controls. Blood samples will be taken and measurements of HbA1c, total cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL) , triglycerides (TG), serum creatinine will be determined by commercial biochemical automatic analyser. A panel of circulating biomarkers will be measured in the blood using commercially available ELISA kits.

Intervention type

Other

Phase

Drug names

Primary outcome measure

Diagnostic accuracy of novel and existing circulating biomarkers for sight threatening retinopathy; the sensitivity, specificity and receiver operating characteristics (ROC) curves will be reported. As it is a cross-sectional study, there is a one-off blood collection, analysis and reporting.

Secondary outcome measures

1. Diagnostic accuracy of novel and existing circulating biomarkers for any diabetic retinopathy
2. Diagnostic accuracy of novel and existing circulating biomarkers for identifying people at risk of microvascular and/or macrovascular complications of diabetes
The sensitivity, specificity and receiver operating characteristics (ROC) curves will be reported. As it is a cross-sectional study, there is a one-off blood collection, analysis and reporting.

Overall trial start date

01/10/2017

Overall trial end date

30/12/2021

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Adults > 40 years of age
2. Ability to give informed consent
3. Patient has to meet ONLY ONE of the criteria below to be included in this study:
3.1. Patient is not diabetic
3.2. Patient is Type 2 DM for > 5 years but no diabetic retinopathy in both eyes
3.3. Mild/Moderate/Severe NPDR with DMO defined as morphological OCT evidence of macular oedema in the worse eye in the last 12 months
3.4. Active PDR with or without diabetic macular oedema in the worse eye (newly diagnosed treatment naïve or being treated with PRP and/or VR surgery in the last 2 years)

Participant type

Mixed

Age group

Adult

Gender

Both

Target number of participants

300

Participant exclusion criteria

1. Type 1 Diabetes Mellitus
2. Type 2 Diabetes Mellitus < 5 years with no diabetic retinopathy
3. Comorbidities such as liver disease, malignancy, acute infections, inflammatory processes, recent surgeries
4. Blood pressure systolic > 180 mmHg or diastolic > 110 mmHg
5. Pregnant and breast feeding women
6. Patient on corticosteroids or immunosuppression
7. Major ocular conditions like uveitis, glaucoma, AMD, vasculitis, occlusion etc in either eye
8. Any ocular conditions other than diabetic retinopathy/maculopathy affecting vision in either eye – for e.g. epiretinal membrane, vitreomacular traction etc
9. Cataract surgery or any ocular surgery in the last 3 months in either eye
10. Significant cataract affecting adequate fundus photographs in either eye
11. Mild/Moderate/Severe NPDR without DMO in worse eye (study eye)

Recruitment start date

01/11/2018

Recruitment end date

01/11/2021

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Moorfields Eye Hospital NHS Foundation Trust
162 City Road
London
EC1V 2PD
United Kingdom

Trial participating centre

Hillingdon Hospitals NHS Foundation Trust
Pield Heath Road Uxbridge
London
UB8 3NN
United Kingdom

Sponsor information

Organisation

Moorfields Eye Hospital NHS Foundation Trust

Sponsor details

162 City Road
London
EC1V 2PD
United Kingdom
+44 (0)2075662818
Maria.Hassard@moorfields.nhs.uk

Sponsor type

Research council

Website

Funders

Funder type

Research council

Funder name

Global Challenge Research Fund, Medical Research Council, UK

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Study protocol and statistical analysis plan will be made available on request. Planned publication of the study results in a high-impact peer reviewed journal.

IPD sharing statement
The datasets generated during and/or analysed during the current study are/will be available upon request from Prof. Sobha Sivaprasad (sobha.sivaprasad@nhs.net). Type of data: fully anonymised processed dataset. The data will become available after the clinical study report is submitted to REC, for 5 years, by written request to Prof. Sobha Sivaprasad and approval obtained from Moorfields Eye Hospital, by encrypted data transfer for analysis on anonymised processed data. Consent from participants was obtained.

Intention to publish date

01/11/2021

Participant level data

Available on request

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes