Lowering Events in Non-proliferative retinopathy in Scotland
| ISRCTN | ISRCTN15073006 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN15073006 |
| EudraCT/CTIS number | 2016-002656-24 |
| ClinicalTrials.gov number | NCT03439345 |
| Secondary identifying numbers | CTSULENS1 |
- Submission date
- 19/02/2018
- Registration date
- 23/02/2018
- Last edited
- 25/06/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nutritional, Metabolic, Endocrine
Plain English Summary
Background and study aims
Each year, 5,500 patients living with diabetes in Scotland need to see an NHS eye specialist because of worsening diabetic retinopathy which is when diabetes affects the inner layer of the eye. Retinopathy leads to the certification of blindness in ~1,400 patients in the UK annually, making it one of the most important causes of blindness in adults of working age. Fenofibrate is a commonly used cholesterol-lowering drug. Two large fenofibrate studies, called FIELD and ACCORD-Lipid, suggested that fenofibrate may well slow down and in some cases stop the progression of retinopathy. However, fenofibrate is not currently used for this reason and there is a need for better information. LENS is designed to provide this information. The aim of this study is to evaluate if fenofibrate therapy will slow the progression of diabetic retinopathy.
Who can participate?
Adults aged 18 and older with diabetes and moderately severe retinopathy in Scotland.
What does the study involve?
Participants are randomly allocated to one of two groups. Those in the first group receive fenofibrate tablet. Those in the second group receive a placebo (an identical dummy) tablet. All study medicine is sent to participants by post. Neither participants nor anyone they may speak to during the trial will know which tablet they are taking (fenofibrate or placebo).This study lasts for approximately six years. Participants are expected to be treated for at least three years and are only required to attend two face-to-face clinic visits, after which all follow-up is conducted using questionnaires by telephone or by computer.
What are the possible benefits and risks of participating?
There are no other direct benefits or risks from taking part in the trial. All treatments have side effects, which some people may experience and others may not. However, fenofibrate is usually well tolerated and it can be taken safely along with the vast majority of other prescribed medicines and it is hoped that the trial will confirm that taking fenofibrate regularly reduces the risk of diabetic eye disease getting worse.
Where is the study run from?
This study is being run by the University of Oxford (UK) and takes place at NHS hospitals throughout all eleven mainland Scottish health boards.
When is the study starting and how long is it expected to run for?
August 2016 to November 2023
Who is funding the study?
National Institute for Health Research (UK)
Who is the main contact?
1. Mrs Sarah Howard (Public)
2. Dr David Preiss (Scientific)
lens@ndph.ox.ac.uk
Contact information
Public
LENS Trial
Richard Doll Building
Old Road Campus
Roosevelt Drive
Oxford
OX3 7LF
United Kingdom
| Phone | +44 (0)1865 743825 |
|---|---|
| lens@ndph.ox.ac.uk |
Scientific
LENS Trial
Richard Doll Building
Old Road Campus
Roosevelt Drive
OXFORD
OX3 7LF
United Kingdom
 ORCID ID |
0000-0003-3139-1836 |
|---|---|
| Phone | +44 (0)1865 743527 |
| lens@ndph.ox.ac.uk |
Study information
| Study design | Multicentre randomized double blind placebo-controlled parallel-group trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised parallel trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Available to download at the trial website |
| Scientific title | A randomised placebo-controlled trial of fenofibrate to prevent progression of non-proliferative retinopathy in diabetes |
| Study acronym | LENS |
| Study hypothesis | Current study hypothesis as of 13/02/2023: The main hypothesis is that fenofibrate therapy will slow the progression of observable diabetic retinopathy/maculopathy to referable diabetic retinopathy/maculopathy or diabetic retinopathy/maculopathy requiring laser treatment or surgical treatment compared with placebo. Previous study hypothesis: The main hypothesis is that fenofibrate therapy will slow the progression of observable diabetic retinopathy/maculopathy to clinically significant diabetic retinopathy/maculopathy or diabetic retinopathy/maculopathy requiring laser treatment or surgical treatment compared with placebo. |
| Ethics approval(s) |
Approved 05/12/2017, West of Scotland Research Ethics Committee (Dykebar Hospital, Grahamston Road, Glasgow, PA2 7DE, United Kingdom; +44 141 3140212; WoSREC1@ggc.scot.nhs.uk), ref: 16/WS/0149 |
| Condition | Diabetic retinopathy |
| Intervention | Eligible participants initially enter an active run-in phase of 6-10 weeks. Thereafter, participants who continue to be eligible are randomized 1:1 to one of two groups by computer-based algorithm. Those in the first group receive the fenofibrate 145mg tablets. Those in the second group receive placebo tablets. Participants with normal renal function (eGFR >=60mL/min/1.73m2) take one tablet daily while participants with evidence of chronic kidney disease (eGFR <60mL/min/1.73m2) take one tablet every second day. Participants are expected to be treated for at least three years and are only required to attend two face-to-face clinic visits, after which all follow-up is conducted using questionnaires by telephone or by computer. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase IV |
| Drug / device / biological / vaccine name(s) | Fenofibrate 145mg, nanoparticle formulation |
| Primary outcome measure | Current primary outcome measure as of 13/02/2023: Number of participants in whom any of the following outcomes occur during the trial: progression from having observable diabetic retinopathy/maculopathy to referable diabetic retinopathy/maculopathy, or requiring any of retinal laser therapy, vitrectomy or intra-vitreal injection of medication due to diabetic retinopathy/maculopathy. Previous primary outcome measure: Number of participants in whom any of the following outcomes occur during the trial: progression from having observable diabetic retinopathy/maculopathy to clinically significant diabetic retinopathy/maculopathy, or requiring any of retinal laser therapy, vitrectomy or intra-vitreal injection of medication due to diabetic retinopathy/maculopathy. |
| Secondary outcome measures | Current secondary outcome measures as of 10/02/2023: 1. Number of participants, respectively, in whom the following outcomes occur during the trial, reported separately: 1.1. Number of participants with progression of diabetic retinopathy/maculopathy to referable diabetic retinopathy/maculopathy (based on the NHS Scotland grading scheme) 1.2. Number of participants requiring retinal laser therapy for diabetic retinopathy/maculopathy (based on patient report and health records) 1.3. Number of participants requiring vitrectomy for diabetic retinopathy/maculopathy (based on patient report and health records) 1.4. Number of participants requiring intra-vitreal injection for diabetic retinopathy/maculopathy (based on the NHS patient report and health records) 2. Any progression of diabetic retinopathy/maculopathy (based on the NHS Scotland's retinal screening grading scheme) 3. Visual acuity measured using LogMAR or Snellen chart measurement (during retinal screening visit) 4. The development of hard exudates or blot haemorrhages within 1 disc diameter of the macula (based on the NHS Scotland's retinal screening grading scheme) 5. The development of macular oedema (based on optical coherence tomography or adverse event report) 6. Visual function measured using the VFQ-25 questionnaire at baseline, approximately 2 years and final assessment 7. Quality of life measured using the EQ-5D questionnaire at baseline, approximately 2 years and final assessment 8. Total cost to the health service based on additional drug treatment and monitoring costs, and health care resource use 9. Cost-effectiveness based on incremental cost per QALY gained with fenofibrate versus placebo Previous secondary outcome measures: 1. Number of participants, respectively, in whom the following outcomes occur during the trial, reported separately: 1.1. Number of participants with progression of diabetic retinopathy/maculopathy to clinically significant diabetic retinopathy/maculopathy (based on the NHS Scotland grading scheme) 1.2. Number of participants requiring retinal laser therapy for diabetic retinopathy/maculopathy (based on patient report and health records) 1.3. Number of participants requiring vitrectomy for diabetic retinopathy/maculopathy (based on patient report and health records) 1.4. Number of participants requiring intra-vitreal injection for diabetic retinopathy/maculopathy (based on the NHS patient report and health records) 2. Any progression of diabetic retinopathy/maculopathy (based on the NHS Scotland's retinal screening grading scheme) 3. Visual acuity measured using LogMAR or Snellen chart measurement (during retinal screening visit) 4. The development of hard exudates within 1 disc diameter of the macula (based on the NHS Scotland's retinal screening grading scheme) 5. The development of macular oedema (based on optical coherence tomography) 6. Visual function is measured using the VFQ-25 questionnaire at baseline, approximately 2 years and final assessment 7. Quality of life is measured using the EQ-5D questionnaire at baseline, approximately 2 years and final assessment 8. Total cost to the health service based on additional drug treatment and monitoring costs, and health care resource use 9. Cost-effectiveness based on incremental cost per QALY gained with fenofibrate versus placebo |
| Overall study start date | 01/08/2016 |
| Overall study end date | 17/11/2023 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | 1060 |
| Total final enrolment | 1151 |
| Participant 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 retinal screening 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 last 3 years) 4. Willing to either complete electronic questionnaires or conduct telephone interviews for collection of data once every 6 months |
| Participant exclusion criteria | Current exclusion criteria as of 16/03/2021: 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 childbearing 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 _____ Previous participant exclusion criteria as of 18/10/2019: 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 _____ Previous participant exclusion criteria: 1. Clinically significant diabetic retinopathy/maculopathy (defined based on NHS Scotland retinal screening grading criteria as R3 or R4 or M2 in one/both eyes) 2. History of gallbladder disease (cholecystitis, symptomatic gallstones, cholecystectomy) 3. History of acute or chronic pancreatitis 4. ALT or AST >2X the upper limit of normal (ULN) 5. CK >3X ULN 6. Estimated glomerular filtration rate <40mL/min/1.73m2 7. Cirrhosis of any aetiology or any other serious hepatic disease 8. Female who is pregnant, breastfeeding, currently trying to become pregnant, or of child-bearing potential and not practising birth control 9. Ongoing vitamin K antagonist (warfarin, phenindione, acenocoumarol), cyclosporine, colchicine, ketoprofen, daptomycin, fibrate therapy or treatment with rosuvastatin 40mg daily 10. Previous myositis, myopathy or rhabdomyolysis of any cause, or diagnosed hereditary muscle disorder 11. Ongoing renal replacement therapy 12. Any previous organ transplant 13. Previous reported intolerance to any fibrate 14. 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) 15. 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 |
| Recruitment start date | 23/07/2018 |
| Recruitment end date | 27/07/2021 |
Locations
Countries of recruitment
- Scotland
- United Kingdom
Study participating centres
Glasgow
G4 0SF
United Kingdom
Glasgow
G51 4TF
United Kingdom
Edinburgh
EH3 9HA
United Kingdom
Dundee
DD1 9SY
United Kingdom
Aberdeen
AB25 2ZN
United Kingdom
Airdrie
ML6 0JS
United Kingdom
East Kilbride
G75 8RG
United Kingdom
Larbert
FK5 4WR
United Kingdom
Dunfermline
KY12 0SU
United Kingdom
Kirkcaldy
KY2 5AH
United Kingdom
Inverness
IV2 3UJ
United Kingdom
Kilmarnock
KA2 0BE
United Kingdom
Ayr
KA6 6DX
United Kingdom
Dumfries
DG1 4AP
United Kingdom
Melrose
TD6 9BQ
United Kingdom
Wishaw
ML2 0DP
United Kingdom
Sponsor information
University/education
Clinical Trials & Research Governance
University of Oxford
Joint Research Office
Churchill Hospital
Oxford
OX3 7LE
England
United Kingdom
| Phone | +44 (0)1865 289885 |
|---|---|
| ctrg@admin.ox.ac.uk | |
| Website | https://researchsupport.admin.ox.ac.uk/ctrg |
"ROR" |
https://ror.org/052gg0110 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 24/06/2024 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | It is intended to publish the main LENS trial results in a high-impact peer-reviewed journal within one year of completion of the trial. The LENS protocol is available at https://www.journalslibrary.nihr.ac.uk/programmes/hta/144984/#/ Updated 03/09/2020: The LENS protocol is attached. |
| IPD sharing plan | Current IPD sharing statement as of 10/02/2023: Data sharing will be conducted in accordance with the Data Access Policy for the Nuffield Department of Population Health, University of Oxford (https://www.ndph.ox.ac.uk/files/about/ndph-data-access-policy-1.pdf). Sharing of data will need to comply with consent provided by participants and with regulations regarding sharing of NHS Scotland data. Previous IPD sharing statement: Data can be requested via the Archive Data Access Coordinator at richard.doll.archive@ndph.ox.ac.uk. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol file | version 6.2 | 29/05/2020 | 03/09/2020 | No | No |
| Protocol file | version 6.3 | 01/06/2021 | 30/07/2021 | No | No |
| Protocol file | version 7.0 | 29/07/2022 | 10/02/2023 | No | No |
| Statistical Analysis Plan | version 1.1 | 13/02/2023 | No | No | |
| HRA research summary | 28/06/2023 | No | No | ||
| Statistical Analysis Plan | version 1.2 | 04/07/2023 | No | No | |
| Statistical Analysis Plan | version 1.3 | 07/02/2024 | 09/02/2024 | No | No |
| Results article | baseline characteristics | 22/02/2024 | 23/02/2024 | Yes | No |
| Results article | primary outcome results | 25/06/2024 | 25/06/2024 | Yes | No |
Additional files
Editorial Notes
25/06/2024: Publication reference added.
23/02/2024: Publication reference added.
09/02/2024: The statistical analysis plan version 1.3 was uploaded.
13/12/2023: The following changes were made to the trial record:
1. The overall end date was changed from 01/12/2023 to 17/11/2023.
2. The intention to publish date was changed from 01/08/2024 to 24/06/2024.
3. The plain English summary was updated to reflect these changes.
4. The IRAS number was added.
04/07/2023: SAP uploaded.
13/02/2023: The study hypothesis and primary outcome measure were updated. The statistical analysis plan was uploaded.
10/02/2023: The following changes were made to the trial record:
1. The latest protocol file was uploaded.
2. The overall trial end date was changed from 01/08/2023 to 01/12/2023.
3. The secondary outcome measures and IPD sharing statement were updated.
05/08/2021: Internal review.
30/07/2021: The latest protocol file was uploaded.
27/07/2021: The following changes were made to the trial record:
1. The recruitment end date was changed from 01/07/2021 to 27/07/2021.
2. The total final enrolment number was added.
16/03/2021: The following changes were made to the trial record:
1. The recruitment end date was changed from 01/03/2021 to 01/07/2021.
2. The exclusion criteria were changed.
03/09/2020: The following changes were made to the trial record:
1. Recruitment to this study is no longer paused.
2. The recruitment end date was changed from 01/09/2020 to 01/03/2021.
3. Uploaded protocol Version 6.2, 29 May 2020 (not peer reviewed).
11/05/2020: Due to current public health guidance, recruitment for this study has been paused. The recruitment end date has been changed from 01/04/2020 to 01/09/2020.
18/10/2019: The following changes were made to the trial record:
1. The exclusion criteria were updated.
2. The recruitment end date was changed from 01/12/2019 to 01/04/2020.
23/05/2019: Perth Royal Infirmary has been removed from the trial participating centres.
02/08/2018: The recruitment start date was changed from 01/04/2018 to 23/07/2018.
