Lowering Events in Non-proliferative Retinopathy in Scotland

NCT ID: NCT03439345

Last Updated: 2025-05-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 1151 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-07-23
• Study Completion Date: 2024-02-16

Brief Summary

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

Detailed 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 randomisation, eligible participants will enter an active run-in phase of 6 to 10 weeks.

Conditions

Diabetic Retinopathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Fenofibrate 145 mg

Name: Fenofibrate; Form: tablet; Dosage: 145 mg; Frequency: One tablet (taken daily with normal renal function, taken every second day with chronic kidney disease)

Group Type: EXPERIMENTAL

Fenofibrate 145 mg

Intervention Type: DRUG

One tablet (taken daily with normal renal function, taken every second day with chronic kidney disease)

Placebo Oral Tablet

Name: Placebo; Form: tablet; Dosage: not applicable; Frequency: One tablet (taken daily with normal renal function, taken every second day with chronic kidney disease)

Group Type: PLACEBO_COMPARATOR

Placebo Oral Tablet

Intervention Type: DRUG

One tablet (taken daily with normal renal function, taken every second day with chronic kidney disease)

Interventions

Fenofibrate 145 mg

One tablet (taken daily with normal renal function, taken every second day with chronic kidney disease)

Intervention Type: DRUG

Placebo Oral Tablet

One tablet (taken daily with normal renal function, taken every second day with chronic kidney disease)

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute for Health Research, United Kingdom

OTHER_GOV

Sponsor Role: collaborator

University of Glasgow

OTHER

Sponsor Role: collaborator

University of Aberdeen

OTHER

Sponsor Role: collaborator

University of Dundee

OTHER

Sponsor Role: collaborator

University of Edinburgh

OTHER

Sponsor Role: collaborator

NHS Scotland Diabetic Retinopathy Screening Collaborative

OTHER

Sponsor Role: collaborator

University of Oxford

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David Preiss, PhD FRCPath

Role: PRINCIPAL_INVESTIGATOR

University of Oxford

Locations

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, , United Kingdom

Countries

United Kingdom

References

LENS Collaborative Group. Design, recruitment and baseline characteristics of the LENS trial. Diabet Med. 2024 Sep;41(9):e15310. doi: 10.1111/dme.15310. Epub 2024 Feb 22.

Reference Type: BACKGROUND

PMID: 38385587 (View on PubMed)

Preiss D, Logue J, Sammons E, Zayed M, Emberson J, Wade R, Wallendszus K, Stevens W, Cretney R, Harding S, Leese G, Currie G, Armitage J. Effect of Fenofibrate on Progression of Diabetic Retinopathy. NEJM Evid. 2024 Aug;3(8):EVIDoa2400179. doi: 10.1056/EVIDoa2400179. Epub 2024 Jun 21.

Reference Type: RESULT

PMID: 38905569 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.ctsu.ox.ac.uk/lens

LENS trial website

Other Identifiers

ISRCTN15073006

Identifier Type: REGISTRY

Identifier Source: secondary_id

CTSULENS1

Identifier Type: -

Identifier Source: org_study_id