Lowering Events in Non-proliferative Retinopathy in Scotland

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

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.

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