Diabetic RetinopathyPhase 4LENSNCT03439345
Lowering Events in Non-proliferative Retinopathy in Scotland
A Phase 4 study testing Fenofibrate 145 mg in people with Diabetic Retinopathy, run by University of Oxford at 16 sites in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetic Retinopathy
- What is being tested?
- Fenofibrate 145 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,151 participants
- Where
- 16 sitesUnited Kingdom
- Study dates
- 23 Jul 2018to 16 Feb 2024
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Capable of giving informed consent
- Diabetes Mellitus (any type except gestational diabetes)
- 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)
- Willing to either complete electronic questionnaires or conduct telephone interviews for collection of data once every 6 months
Who cannot join
- Clinically significant DR (defined as R3 or R4 or M2 in one or both eyes)
- History of gallbladder disease (cholecystitis, symptomatic gallstones, cholecystectomy)
- History of acute or chronic pancreatitis
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2X the upper limit of normal (ULN) according to local NHS laboratory reference range at screening visit
- ALT or AST >2.5X ULN according to local NHS laboratory reference range at randomisation visit
- Creatine kinase (CK) >3X ULN according to local NHS laboratory reference range at screening visit
Show all 20Show fewer
- CK >3X ULN according to local NHS laboratory reference range at randomisation visit
- Estimated glomerular filtration rate (eGFR) <40mL/min/1.73m2 at screening visit
- eGFR <30mL/min/1.73m2 at randomisation visit
- Cirrhosis of any aetiology or any other serious hepatic disease (investigator opinion)
- Female who is pregnant, breastfeeding, currently trying to become pregnant, or of child-bearing potential and not practising birth control
- Ongoing vitamin K antagonist (warfarin, phenindione, acenocoumarol), cyclosporine, colchicine, ketoprofen, daptomycin, fibrate therapy, or treatment with rosuvastatin 40mg daily
- Previous myositis, myopathy or rhabdomyolysis of any cause, or diagnosed hereditary muscle disorder
- Ongoing renal replacement therapy
- Any previous organ transplant
- Previous reported intolerance to any fibrate
- 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)
- 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
- 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.
- Not adherent to active run-in treatment
Trial locations and contacts
16 sites in 1 country.
16 sites in 1 country
United Kingdom16 sites
NHS Grampian
Aberdeen
NHS Lanarkshire
Airdrie
NHS Ayrshire and Arran
Ayr
NHS Dumfries and Galloway
Dumfries
NHS Tayside
Dundee
NHS Fife
Dunfermline
NHS Lanarkshire
East Kilbride
NHS Lothian
Edinburgh
NHS Greater Glasgow and Clyde
Glasgow
NHS Highland
Inverness
NHS Ayrshire and Arran
Kilmarnock
NHS Fife
Kirkcaldy
NHS Forth Valley
Larbert
NHS Borders
Melrose
NHS Tayside
Perth
NHS Lanarkshire
Wishaw
About this study
Official title: A Randomised Placebo-controlled Trial of Fenofibrate to Prevent Progression of Non-proliferative Retinopathy in Diabetes
LENS is a streamlined multicentre randomised placebo-controlled parallel-group trial investigating the effect of fenofibrate treatment on the progression of diabetic retinopathy/maculopathy.
Read the 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
- Being tested
- Fenofibrate 145 mg, Placebo Oral Tablet
- Medical subject headings
- Diabetic Retinopathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fenofibrate 145 mgDrug
One tablet (taken daily with normal renal function, taken every second day with chronic kidney disease)
Placebo Oral TabletDrug
One tablet (taken daily with normal renal function, taken every second day with chronic kidney disease)
| Study group | Role | What they receive |
|---|---|---|
| Fenofibrate 145 mg | Experimental | Name: Fenofibrate; Form: tablet; Dosage: 145 mg; Frequency: One tablet (taken daily with normal renal function, taken every second day with chronic kidney disease) Receives: Drug: Fenofibrate 145 mg |
| Placebo Oral Tablet | Placebo comparator | Name: Placebo; Form: tablet; Dosage: not applicable; Frequency: One tablet (taken daily with normal renal function, taken every second day with chronic kidney disease) Receives: Drug: Placebo Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment
Primary outcome was a composite of the development of referable diabetic retinopathy or referable maculopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). Referable diabetic retinopathy was defined by the NHS Scotland's grading criteria as any development of R3, R4 or M2 disease. R3 (referable background diabetic retinopathy): any of four or more blot hemorrhages in both inferior and superior hemi-fields, or venous beading, or intraretinal microvascular abnormalities (IRMA); R4 (proliferative diabetic retinopathy): any active new vessels, or vitreous hemorrhage; M2 (referable maculopathy): any blot hemorrhages, or hard exudates within a radius of ≤1 optic disc diameter of the centre of the fovea. Adverse event reports of eye procedures, vitreous haemorrhages and macular oedema were adjudicated by experienced doctors at the Central Co-ordinating Office (CCO), masked to treatment allocation.
Measured: 4.0 years (interquartile range, 3.6 to 4.3) years
Secondary outcomes (24)
Number of Participants With the Individual Component of the Composite Primary Outcome: Development of Referable Diabetic Retinopathy or Maculopathy
Progression of Diabetic Retinopathy/Maculopathy to a referable grade (R3 or R4 or M2) based on the NHS Scotland grading scheme in at least one eye.
Measured: 4.0 years (interquartile range, 3.6 to 4.3) years
Number of Participants With the Individual Component of Composite Primary Outcome: Treatment for Diabetic Retinopathy or Maculopathy
Treatment for diabetic retinopathy or maculopathy (including intravitreal injection of medication, retinal laser therapy, or vitrectomy) in either eye.
Measured: 4.0 years (interquartile range, 3.6 to 4.3) years
Number of Participants With Any Progression of Diabetic Retinopathy or Maculopathy Across the NHS Scotland Retinopathy Grading Scale
Any progression of diabetic retinopathy or maculopathy across the NHS Scotland retinopathy grading scale. R4 = Proliferative DR, R3 = Referable background DR, R2 = Observable background DR. R1 = Mild background DR, R0 = No DR anywhere (where R4 is the highest severity grade and R0 is the lowest grade); M2 = Referable maculopathy, M1 = Observable maculopathy, M0 = No Maculopathy (where M2 is the highest severity grade and M0 is the lowest grade).
Measured: 4.0 years (interquartile range, 3.6 to 4.3) years
Number of Participants With Referable Maculopathy (Exudates or Blot Haemorrhages Within One Disc Diameter of the Fovea)
The presence of hard exudates or blot haemorrhages within 1 disc diameter of the macula/fovea
Measured: 4.0 years (interquartile range, 3.6 to 4.3) years
Number of Participants With The Development of Macular Oedema
The accumulation of macular fluid as determined by optical coherence tomography (OCT) imaging or on adverse event report
Measured: 4.0 years (interquartile range, 3.6 to 4.3) years
Visual Acuity
Based on measurement of visual acuity at retinal screening visits. Baseline visual acuity was taken from routine measurement within NHS Scotland's Diabetic Eye Screening programme (using the latest value within 18 months of randomisation). Visual acuity after randomisation was obtained by averaging available results for a participant. Conversion from Snellen to LogMAR was applied where necessary. This analysis is based on the better eye: if only 1 eye with results, analyse that eye; if 2 eyes, use eye with better acuity; if identical acuity in both eyes, use the right eye. LogMAR typically ranges from -0.3 (20/10 vision on the Snellen chart) to 1 (20/200 vision). Lower scores indicate better vision.
Measured: 4.0 years (interquartile range, 3.6 to 4.3) years
Visual Function, Based on the National Eye Institute Visual Functioning Questionnaire 25 (VFQ-25).
Visual function is based on the Visual Function Questionnaire-25. Visual function was defined by the composite score derived from the VFQ-25. VFQ-25 data were collected at the screening visit, after two years and at the end of the study. Results from two years and end-of-study were averaged to provide a trial-averaged result for a participant. The VFQ-25 composite score ranges from 0 to 100, where higher scores indicate better visual function. It is calculated by averaging results from up to 11 vision-related sub-scales.
Measured: 4.0 years (interquartile range, 3.6 to 4.3) years
Quality of Life, Based on the EQ-5D Index Score
Quality of life was measured using the EQ-5D instrument, and valued by mapping to the EQ-5D-3L UK value set using the mapping function developed by Hernandez Alava et al. Pharmaco Economics (2022). EQ-5D data were collected at the screening visit, after two years and at the end of the study. Results from two years and end-of-study were averaged to provide a trial-averaged result for a participant. Possible scores range from -0.59 to 1.00, where 1 is the best possible health state and 0 represents a quality of life considered equivalent to death.
Measured: 4.0 years (interquartile range, 3.6 to 4.3) years
Quality of Life, Based on the EQ-5D Visual Analogue Scale.
EQ-5D Visual Analogue Scale data were collected at the screening visit, after two years and at the end of the study. Results from two years and end-of-study were averaged to provide a trial-averaged result for a participant. EQ VAS scores range from 0 to 100, where 100 is the best possible health state.
Measured: 4.0 years (interquartile range, 3.6 to 4.3) years
Cost to the Health Service
Health economic analysis: cost to the health service over 2 years. This included (i) hospital inpatient and outpatient activity (costed with nationally representative NHS costs); (ii) costs of fenofibrate (based on 200mg NHS cost); (iii) laboratory tests (NHS cost (including nurse/doctor time)); (iv) community prescribed medicines (NHS costs); (v) NHS Scotland retinal screening (published NHS unit costs); (vi) treatment for advanced retinopathy: for relevant participants, application of assumptions regarding usual number of injections from UK cohort study.
Measured: 2 years
Cost-effectiveness (Incremental Cost Per QALY Gained)
Health economic analysis: Cost-effectiveness (incremental cost per QALY gained). The result is the value of GBP (British Pound) expenditure required to gain 1 quality adjusted life year for fenofibrate therapy vs. standard care. Years gained are presented by arm with 95% credible intervals taken as 2.5th and 97.5th percentile of simulated probabilistic output.
Measured: Projected over 10 year horizon
Number of Participants in Subgroup Sex - Male With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment
Composite primary outcome in prespecified subgroup according to the baseline characteristic: Sex - male. The primary outcome was a composite of the development of referable diabetic retinopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). The definition for referable diabetic retinopathy is provided above in '1. Primary Outcome: Number of Participants with Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.
Measured: 4.0 years (interquartile range, 3.6 to 4.3) years
Number of Participants in Subgroup Sex - Female With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment
Composite primary outcome in prespecified subgroup according to the baseline characteristic: Sex - female. The primary outcome was a composite of the development of referable diabetic retinopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). The definition for referable diabetic retinopathy is provided above in '1. Primary Outcome: Number of Participants with Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.
Measured: 4.0 years (interquartile range, 3.6 to 4.3) years
Number of Participants in Subgroup Age <60y With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment
Composite primary outcome in prespecified subgroup according to the baseline characteristic: Age <60 years. The primary outcome was a composite of the development of referable diabetic retinopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). The definition for referable diabetic retinopathy is provided above in '1. Primary Outcome: Number of Participants with Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.
Measured: 4.0 years (interquartile range, 3.6 to 4.3) years
Number of Participants in Subgroup Age ≥60y With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.
Composite primary outcome in prespecified subgroup according to the baseline characteristic: Age ≥60 years. The primary outcome was a composite of the development of referable diabetic retinopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). The definition for referable diabetic retinopathy is provided above in '1. Primary Outcome: Number of Participants with Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.
Measured: 4.0 years (interquartile range, 3.6 to 4.3) years
Number of Participants in Subgroup - Type 1 Diabetes With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment
Composite primary outcome in prespecified subgroup according to the baseline characteristic: Type of Diabetes - type 1 diabetes. The primary outcome was a composite of the development of referable diabetic retinopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). The definition for referable diabetic retinopathy is provided above in '1. Primary Outcome: Number of Participants with Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.
Measured: 4.0 years (interquartile range, 3.6 to 4.3) years
Number of Participants in Subgroup - Type 2 or Other Type of Diabetes With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment
Composite primary outcome in prespecified subgroup according to the baseline characteristic: Type 2 and other diabetes. The primary outcome was a composite of the development of referable diabetic retinopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). The definition for referable diabetic retinopathy is provided above in '1. Primary Outcome: Number of Participants with Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.
Measured: 4.0 years (interquartile range, 3.6 to 4.3) years
Number of Participants in Subgroup - eGFR <60 mL/Min/1.73m^2 With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment
Primary outcome in prespecified subgroup according to the baseline characteristic: Renal function at Randomisation - eGFR <60mL/min/1.73m^2). The primary outcome was a composite of the development of referable diabetic retinopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). The definition for referable diabetic retinopathy is provided above in '1. Primary Outcome: Number of Participants with Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.
Measured: 4.0 years (interquartile range, 3.6 to 4.3) years
Number of Participants in Subgroup - eGFR ≥60 mL/Min/1.73m^2 With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment
Composite primary outcome in prespecified subgroup according to the baseline characteristic: Renal function at Randomisation - eGFR ≥60mL/min/1.73m^2. The primary outcome was a composite of the development of referable diabetic retinopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). The definition for referable diabetic retinopathy is provided above in '1. Primary Outcome: Number of Participants with Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.
Measured: 4.0 years (interquartile range, 3.6 to 4.3) years
Number of Participants in Subgroup - HbA1c <70 mmol/Mol With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment
Primary outcome in prespecified subgroup according to the baseline characteristic: HbA1c at Screening <70mmol/mol. The primary outcome was a composite of the development of referable diabetic retinopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). The definition for referable diabetic retinopathy is provided above in '1. Primary Outcome: Number of Participants with Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.
Measured: 4.0 years (interquartile range, 3.6 to 4.3) years
Number of Participants in Subgroup - HbA1c ≥70 mmol/Mol With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment
Primary outcome in prespecified subgroup according to the baseline characteristic-HbA1c at Screening - ≥70mmol/mol. The primary outcome was a composite of the development of referable diabetic retinopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). The definition for referable diabetic retinopathy is provided above in '1. Primary Outcome: Number of Participants with Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.
Measured: 4.0 years (interquartile range, 3.6 to 4.3) years
Number of Participants in Subgroup - HbA1c Unknown With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment
Composite primary outcome in prespecified subgroup according to the baseline characteristic - HbA1c at Screening - Unknown. The primary outcome was a composite of the development of referable diabetic retinopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). The definition for referable diabetic retinopathy is provided above in '1. Primary Outcome: Number of Participants with Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.
Measured: 4.0 years (interquartile range, 3.6 to 4.3) years
Number of Participants in Subgroup With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment, Within 1 Year of Randomization
Composite primary outcome in prespecified subgroup according to the baseline characteristic: Timing of primary outcome - Within first year. The primary outcome was a composite of the development of referable diabetic retinopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). The definition for referable diabetic retinopathy is provided above in '1. Primary Outcome: Number of Participants with Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.
Measured: Up to 1 year from randomisation.
Number of Participants in Subgroup With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment, After 1 Year From Randomization
Composite primary outcome in prespecified subgroup according to the baseline characteristic: Timing - After first year. The primary outcome was a composite of the development of referable diabetic retinopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). The definition for referable diabetic retinopathy is provided above in '1. Primary Outcome: Number of Participants with Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.
Measured: 4.0 years (interquartile range, 3.6 to 4.3) years, excluding any primary outcome events within the first year of randomisation.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2018
- Study start23 Jul 2018
- Primary completion17 Nov 2023
- Study completion16 Feb 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Diabetic RetinopathyStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,151 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute for Health Research, United Kingdom, University of Glasgow, University of Aberdeen, University of Dundee, University of Edinburgh, NHS Scotland Diabetic Retinopathy Screening Collaborative
- Responsible party
- Sponsor
- Investigators
- David Preiss, PhD FRCPath, Principal investigator, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03439345
- Sponsor's protocol ID
- CTSULENS1
- Other IDs
- ISRCTN15073006
- Acronym
- LENS
- Status last verified
- Jan 2025
- First submitted
- 5 Feb 2018
- Last updated
- 14 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data generated by LENS will be available on application to bona fide academic researchers in accordance with the Data Access Policy for the Nuffield Department of Population Health, University of Oxford. Such approvals will also need to be consistent with the informed consent provided by participants. Any sharing of data derived from NHS Scotland data will need to comply with the approvals of the trial.
Publications
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.
PubMed 38385587Preiss 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.
PubMed 38905569
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised Placebo-controlled Trial of Fenofibrate to Prevent Progression of Non-proliferative Retinopathy in Diabetes
- ClinicalTrials.gov ID
- NCT03439345
- Acronym / sponsor ID
- LENS / CTSULENS1
- Conditions
- Diabetic Retinopathy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,151 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- National Institute for Health Research, United Kingdom, University of Glasgow, University of Aberdeen, University of Dundee, University of Edinburgh, NHS Scotland Diabetic Retinopathy Screening Collaborative
- Study start
- 23 Jul 2018 (actual)
- Primary completion
- 17 Nov 2023 (actual)
- Study completion
- 16 Feb 2024 (actual)
- First posted
- 20 Feb 2018 (actual)
- Results
- Posted 14 May 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fenofibrate 145 mg | Experimental | Drug: Fenofibrate 145 mgName: Fenofibrate; Form: tablet; Dosage: 145 mg; Frequency: One tablet (taken daily with normal renal function, taken every second day with chronic kidney disease) |
| Placebo Oral Tablet | Placebo comparator | Drug: Placebo Oral TabletName: Placebo; Form: tablet; Dosage: not applicable; Frequency: One tablet (taken daily with normal renal function, taken every second day with chronic kidney disease) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Capable of giving informed consent
- Diabetes Mellitus (any type except gestational diabetes)
- 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)
- Willing to either complete electronic questionnaires or conduct telephone interviews for collection of data once every 6 months
Key exclusion criteria (20 listed)
- Clinically significant DR (defined as R3 or R4 or M2 in one or both eyes)
- History of gallbladder disease (cholecystitis, symptomatic gallstones, cholecystectomy)
- History of acute or chronic pancreatitis
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2X the upper limit of normal (ULN) according to local NHS laboratory reference range at screening visit
- ALT or AST >2.5X ULN according to local NHS laboratory reference range at randomisation visit
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fenofibrate 145 mgOne tablet (taken daily with normal renal function, taken every second day with chronic kidney disease) | Drug | Fenofibrate 145 mg |
| Placebo Oral TabletOne tablet (taken daily with normal renal function, taken every second day with chronic kidney disease) | Drug | Placebo Oral Tablet |
Primary outcome
Number of Participants With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment
Time frame: 4.0 years (interquartile range, 3.6 to 4.3) years
Primary outcome was a composite of the development of referable diabetic retinopathy or referable maculopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). Referable diabetic retinopathy was defined by the NHS Scotland's grading criteria as any development of R3, R4 or M2 disease. R3 (referable background diabetic retinopathy): any of four or more blot hemorrhages in both inferior and superior hemi-fields, or venous beading, or intraretinal microvascular abnormalities (IRMA); R4 (proliferative diabetic retinopathy): any active new vessels, or vitreous hemorrhage; M2 (referable maculopathy): any blot hemorrhages, or hard exudates within a radius of ≤1 optic disc diameter of the centre of the fovea. Adverse event reports of eye procedures, vitreous haemorrhages and macular oedema were adjudicated by experienced doctors at the Central Co-ordinating Office (CCO), masked to treatment allocation.
24 secondary outcomes
Number of Participants With the Individual Component of the Composite Primary Outcome: Development of Referable Diabetic Retinopathy or Maculopathy
Time frame: 4.0 years (interquartile range, 3.6 to 4.3) years
Number of Participants With the Individual Component of Composite Primary Outcome: Treatment for Diabetic Retinopathy or Maculopathy
Time frame: 4.0 years (interquartile range, 3.6 to 4.3) years
Number of Participants With Any Progression of Diabetic Retinopathy or Maculopathy Across the NHS Scotland Retinopathy Grading Scale
Time frame: 4.0 years (interquartile range, 3.6 to 4.3) years
Number of Participants With Referable Maculopathy (Exudates or Blot Haemorrhages Within One Disc Diameter of the Fovea)
Time frame: 4.0 years (interquartile range, 3.6 to 4.3) years
Number of Participants With The Development of Macular Oedema
Time frame: 4.0 years (interquartile range, 3.6 to 4.3) years
Visual Acuity
Time frame: 4.0 years (interquartile range, 3.6 to 4.3) years
Visual Function, Based on the National Eye Institute Visual Functioning Questionnaire 25 (VFQ-25).
Time frame: 4.0 years (interquartile range, 3.6 to 4.3) years
Quality of Life, Based on the EQ-5D Index Score
Time frame: 4.0 years (interquartile range, 3.6 to 4.3) years
Quality of Life, Based on the EQ-5D Visual Analogue Scale.
Time frame: 4.0 years (interquartile range, 3.6 to 4.3) years
Cost to the Health Service
Time frame: 2 years
Cost-effectiveness (Incremental Cost Per QALY Gained)
Time frame: Projected over 10 year horizon
Number of Participants in Subgroup Sex - Male With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment
Time frame: 4.0 years (interquartile range, 3.6 to 4.3) years
Number of Participants in Subgroup Sex - Female With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment
Time frame: 4.0 years (interquartile range, 3.6 to 4.3) years
Number of Participants in Subgroup Age <60y With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment
Time frame: 4.0 years (interquartile range, 3.6 to 4.3) years
Number of Participants in Subgroup Age ≥60y With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.
Time frame: 4.0 years (interquartile range, 3.6 to 4.3) years
Number of Participants in Subgroup - Type 1 Diabetes With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment
Time frame: 4.0 years (interquartile range, 3.6 to 4.3) years
Number of Participants in Subgroup - Type 2 or Other Type of Diabetes With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment
Time frame: 4.0 years (interquartile range, 3.6 to 4.3) years
Number of Participants in Subgroup - eGFR <60 mL/Min/1.73m^2 With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment
Time frame: 4.0 years (interquartile range, 3.6 to 4.3) years
Number of Participants in Subgroup - eGFR ≥60 mL/Min/1.73m^2 With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment
Time frame: 4.0 years (interquartile range, 3.6 to 4.3) years
Number of Participants in Subgroup - HbA1c <70 mmol/Mol With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment
Time frame: 4.0 years (interquartile range, 3.6 to 4.3) years
Number of Participants in Subgroup - HbA1c ≥70 mmol/Mol With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment
Time frame: 4.0 years (interquartile range, 3.6 to 4.3) years
Number of Participants in Subgroup - HbA1c Unknown With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment
Time frame: 4.0 years (interquartile range, 3.6 to 4.3) years
Number of Participants in Subgroup With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment, Within 1 Year of Randomization
Time frame: Up to 1 year from randomisation.
Number of Participants in Subgroup With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment, After 1 Year From Randomization
Time frame: 4.0 years (interquartile range, 3.6 to 4.3) years, excluding any primary outcome events within the first year of randomisation.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 38385587LENS 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.
- Results publication: PubMed 38905569Preiss 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.
- LENS trial websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Data generated by LENS will be available on application to bona fide academic researchers in accordance with the Data Access Policy for the Nuffield Department of Population Health, University of Oxford. Such approvals will also need to be consistent with the informed consent provided by participants. Any sharing of data derived from NHS Scotland data will need to comply with the approvals of the trial.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Preiss, PhD FRCPath principal investigator
University of Oxford
16 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Fenofibrate 145 mg in people with Diabetic Retinopathy, run by University of Oxford at 16 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment (time frame: 4.0 years (interquartile range, 3.6 to 4.3) years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03439345, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2025.