Lowering Events in Non-proliferative Retinopathy in Scotland

Diabetic Retinopathy Clinical Trial

— LENS  

Official title:

A Randomised Placebo-controlled Trial of Fenofibrate to Prevent Progression of Non-proliferative Retinopathy in Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03439345
• Other study ID #: CTSULENS1
• Status: Completed
• Phase: Phase 4
• Start date: July 23, 2018
• Est. completion date: February 16, 2024

Study information

• Verified date: February 2024
• Source: University of Oxford
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

LENS is a streamlined multicentre randomized placebo-controlled parallel-group trial investigating the effect of fenofibrate treatment on the progression of diabetic retinopathy/maculopathy

Description:

LENS is a phase 4 randomised placebo-controlled clinical trial of fenofibrate in participants with diabetes and observable retinopathy or maculopathy. The trial aims to recruit approximately 1,060 participants and to treat them for a median duration of at least 4 years. The main aim of LENS is to investigate the effect of fenofibrate therapy on progression to referable diabetic retinopathy/maculopathy. The trial will be conducted using a pragmatic streamlined trial design with the only planned face-to-face visits being an initial screening visit, followed by a randomisation visit eight weeks later. Contact with participants thereafter will be by means of regular telephone or computer questionnaire, and outcome and safety data will also be sought by means of linkage to NHS Scotland registries. Prior to randomization, eligible participants will enter an active run-in phase of 6 to 10 weeks.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1151
• Est. completion date: February 16, 2024
• Est. primary completion date: November 17, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Capable of giving informed consent

2. Diabetes Mellitus (any type except gestational diabetes)

3. Observable diabetic retinopathy/maculopathy (defined based on NHS Scotland grading criteria as: R1 in both eyes or R2 in one/both eyes at the most recent retinal screening assessment; or M1 in one/both eyes at any retinal screening assessment in the 3 years)

4. Willing to either complete electronic questionnaires or conduct telephone interviews for collection of data once every 6 months

Exclusion Criteria:

1. Clinically significant DR (defined as R3 or R4 or M2 in one or both eyes)

2. History of gallbladder disease (cholecystitis, symptomatic gallstones, cholecystectomy)

3. History of acute or chronic pancreatitis

4. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2X the upper limit of normal (ULN) according to local NHS laboratory reference range at screening visit

5. ALT or AST >2.5X ULN according to local NHS laboratory reference range at randomisation visit

6. Creatine kinase (CK) >3X ULN according to local NHS laboratory reference range at screening visit

7. CK >3X ULN according to local NHS laboratory reference range at randomisation visit

8. Estimated glomerular filtration rate (eGFR) <40mL/min/1.73m2 at screening visit

9. eGFR <30mL/min/1.73m2 at randomisation visit

10. Cirrhosis of any aetiology or any other serious hepatic disease (investigator opinion)

11. Female who is pregnant, breastfeeding, currently trying to become pregnant, or of child-bearing potential and not practising birth control

12. Ongoing vitamin K antagonist (warfarin, phenindione, acenocoumarol), cyclosporine, colchicine, ketoprofen, daptomycin, fibrate therapy, or treatment with rosuvastatin 40mg daily

13. Previous myositis, myopathy or rhabdomyolysis of any cause, or diagnosed hereditary muscle disorder

14. Ongoing renal replacement therapy

15. Any previous organ transplant

16. Previous reported intolerance to any fibrate

17. Medical history that might limit the individual's ability to take trial treatments for the duration of the study (e.g. severe respiratory disease, history of cancer within last 5 years other than non-melanoma skin cancer; or recent history of alcohol or substance misuse)

18. Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participant at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial

19. LENS participants can participate in other research studies, including clinical trials. The only exclusions related to co-enrolment will be: if any other study or trial excludes co-enrolment or if the intervention being investigated in another trial has the potential to interact with fenofibrate therapy.

20. Not adherent to active run-in treatment

Related Conditions & MeSH terms

• Diabetic Retinopathy
• Retinal Diseases

Intervention

Drug:
• Fenofibrate 145 mg
One tablet (taken daily with normal renal function, taken every second day with chronic kidney disease)
• Placebo Oral Tablet
One tablet (taken daily with normal renal function, taken every second day with chronic kidney disease)

Locations

Country	Name	City	State
United Kingdom	NHS Grampian	Aberdeen
United Kingdom	NHS Lanarkshire	Airdrie
United Kingdom	NHS Ayrshire and Arran	Ayr
United Kingdom	NHS Dumfries and Galloway	Dumfries
United Kingdom	NHS Tayside	Dundee
United Kingdom	NHS Fife	Dunfermline
United Kingdom	NHS Lanarkshire	East Kilbride
United Kingdom	NHS Lothian	Edinburgh
United Kingdom	NHS Greater Glasgow and Clyde	Glasgow
United Kingdom	NHS Highland	Inverness
United Kingdom	NHS Ayrshire and Arran	Kilmarnock
United Kingdom	NHS Fife	Kirkcaldy
United Kingdom	NHS Forth Valley	Larbert
United Kingdom	NHS Borders	Melrose
United Kingdom	NHS Tayside	Perth
United Kingdom	NHS Lanarkshire	Wishaw

Sponsors (7)

Lead Sponsor	Collaborator
University of Oxford	National Institute for Health Research, United Kingdom, NHS Scotland Diabetic Retinopathy Screening Collaborative, University of Aberdeen, University of Dundee, University of Edinburgh, University of Glasgow

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in urine albumin:creatinine ratio	Based on collection of biochemical data	Approximately 4 years
Other	The occurrence of major cardiovascular events (myocardial infarction, stroke, coronary and peripheral revascularisation)	Based on patient history and medical records	Approximately 4 years
Other	Minor and major non-traumatic lower limb amputation (minor [defined as distal to the ankle] or major [defined as through or proximal to the ankle])	Based on patient history and medical records	Approximately 4 years
Primary	Progression to referable diabetic retinopathy/maculopathy	The composite of progression to referable diabetic retinopathy/maculopathy or any of retinal laser therapy, vitrectomy or intra-vitreal injection of medication for the treatment of diabetic retinopathy/maculopathy; Referable diabetic retinopathy is defined according to NHS Scotland's grading criteria.	Approximately 4 years
Secondary	Components of the primary outcome (progression to referable diabetic retinopathy/maculopathy; retinal laser therapy; vitrectomy; intra-vitreal injection of medication for treatment of diabetic retinopathy/maculopathy) reported separately	Number of participants, respectively, in whom the following outcomes occur, reported separately: Number of participants with progression of diabetic retinopathy/maculopathy to referable diabetic retinopathy/maculopathy (based on the NHS Scotland grading scheme); Number of participants requiring retinal laser therapy for diabetic retinopathy/maculopathy (based on patient report and health records); Number of participants requiring vitrectomy for diabetic retinopathy/maculopathy (based on the NHS patient report and health records); Number of participants requiring intra-vitreal injection for diabetic retinopathy/maculopathy (based on the NHS patient report and health records)	Approximately 4 years
Secondary	Any progression of diabetic retinopathy/maculopathy	Based on the NHS Scotland grading scheme	Approximately 4 years
Secondary	Visual acuity	Based on measurement of visual acuity at retinal screening visits	Approximately 4 years
Secondary	The development of hard exudates or haemorrhages within 1 disc diameter of the macula	Based on the NHS Scotland grading scheme	Approximately 4 years
Secondary	The development of macular oedema	The accumulation of macular fluid as determined by optical coherence tomography (OCT) imaging or on adverse event report	Approximately 4 years
Secondary	Visual function (according to the VFQ-25 questionnaire)	According to the VFQ-25 questionnaire	Approximately 4 years
Secondary	Quality of life (according to the EQ-5D questionnaire)	According to the EQ-5D questionnaire	Approximately 4 years
Secondary	Total cost to the health service	Health economic analysis	Approximately 4 years
Secondary	Cost-effectiveness (incremental cost per QALY gained)	Health economic analysis	Approximately 4 years

External Links

•   LENS trial website