Noctura400 Treatment for Diabetic Retinopathy (CANDLE) (CANDLE)

Noctura400 Treatment for Diabetic Retinopathy: Pilot Study to Demonstrate and Evaluate the Care Pathway for National Health Service (NHS) Adoption

In this study, the investigators aim to use light masks (Noctura 400) to test the hypothesis that preventing the dark adaptation and associated hypoxia of the rods in the eye could in turn prevent or halt the progression of centre-involving Diabetic Macular Oedema (DMO). DMO is a devastating disease that is the most common cause of registerable blindness in the working age-group in the United Kingdom (UK)

This is a multi-centred randomised controlled trial involving 240 patients. Post randomization, participants in the intervention arm will wear the Noctura 400 Light Mask at night for 48 weeks in conjunction with their routine, prescribed treatment of intravitreal (eye) ranibizumab. Those in the standard arm will receive their routine, prescribed ranibizumab treatment only.

The primary objective is to determine whether utilizing the Noctura 400 Light Mask at night reduces the number of intravitreal injections of ranibizumab required by patients undergoing such a course for the treatment of DMO.

Study Overview

• Status: Terminated
• Conditions: Diabetic Macular Oedema
• Intervention / Treatment: Drug: Ranibizumab; Device: Noctura 400 Eye Mask

Detailed Description

Diabetes is regarded by the World Health Organisation (WHO) as a global epidemic, with the global diabetic population anticipated to exceed 500 million by 2020. In the UK there are over 3.5 million people who have diabetes with a growth rate exceeding 150,000 people per year. Diabetic Retinopathy (DR) is the most common complication of diabetes, and the most common cause of sight threatening retinopathy is Diabetic Macular Oedema (DMO).

This condition is characterised by leakage of fluid from compromised blood vessels in the central retina and 240,000 (8%) people with diabetes in the UK have clinically significant DMO, and 100,000 people with DMO have visual impairment. DMO is the most common cause of registerable blindness in the working age-group in the UK. The Diabetic Eye Screening Programme (DESP) annually photographs 3 million people with diabetes at a cost of £65 million to ensure early diagnosis of these sight threatening complications. All patients with diabetic maculopathy are referred to the Hospital Eye Service (HES).

Clinically significant macular oedema requires treatment. Non-central oedema is usually kept under close monitoring or laser treatment is advocated. Centre involving macular oedema is usually treated with intravitreal injections of inhibitors of Vascular Endothelial Growth Factor (anti-VEGF). Whilst laser treatment can reduce the risk of moderate visual loss by 50%, it is not effective in restoring best corrected visual acuity (BCVA) and has significant, quality of life impacting side effects. The anti-VEGF treatments are costly and cause significant burden to patients, their care-givers and the healthcare system.

A patient with DR never leaves the HES. With diabetes on the rise the cost of care for this ever increasing population is growing year on year. This is putting immense strain on the resources and budgets of the healthcare system.

In this trial the investigators will explore the health and economic impact of a new, novel therapy for DMO provided by the Noctura 400 Light Mask. The Light Mask provides a non-invasive, light therapy that can be administered at home by the patients themselves. If successful, the introduction of Noctura 400 Light Mask treatment could bring significant benefits to both patients and the healthcare system.

This trial has been designed as a randomised control trial to allow the direct assessment of the Noctura 400 treatment based on a comparison with a control arm of patients not receiving this treatment. All participants in the trial will be due to undergo their first year of a course of intravitreal injection of an anti-VEGF drug known as ranibizumab. Those in the treatment arm will, in addition to this course of injections, wear the Noctura 400 Light Mask each night for 48 weeks. Those in the standard, or control, arm will receive their course of injections only.

The study will involve 240 participants who have been diagnosed with clinically significant DMO and referred to the Hospital Eye Service (HES) for injections. The current threshold for referral is central retinal thickening of 400um or greater. Once in the HES, potential participants will be assessed for eligibility in clinic. These eligibility tests will form the future participant's "baseline visit". If eligible, patients will be invited to participate in the study. The eligibility assessment requires no further tests to those required by the routine care pathway.

After gaining informed consent, eligible and consenting participants will then be randomised into either the intervention arm (those wearing the Noctura 400 Light Mask each night in conjunction with their routine injections) or a standard arm (those receiving their injections only) and will then be invited back to clinic to begin their allocated therapy.

At the first trial visit, those in the intervention arm will be given the Noctura 400 Light Mask to take away with them and instructed how to use it. The Noctura 400 is powered and programmed to last for precisely 12 weeks. Participants will be provided with a replacement mask at appropriate appointments to ensure continuous treatment.

At each and every appointment all participants will undergo Optical Coherence Tomography (OCT) measurements (for assessment of disease progression) and visual acuity (VA) tests. For the first three visits all participants will be given intravitreal injections, following this, participants in both arms will be given injections at appointments only if required based on the results of the OCT and VA tests. Medical history, concomitant medications and adverse events will be recorded at each visit. At weeks 0,12 and 48 patients will fill out insomnia and sleepiness and quality of life questionnaires.

The Noctura 400 has the ability to sense and record when it has been used as a direct measure of compliance. Sleep Mask data will be collected at weeks 12,24,26 and 48. If compliance is low this will be discussed with the participant with the aim of increasing compliance. If at any point during the trial the Noctura 400 Light Mask appears faulty it will be returned for analysis and replaced.

The trial ends at the patient's last visit after 48 weeks of use. Participants will return their Noctura 400 Light Masks for analysis and then patients in both arms are free to continue their routine injections as prescribed by the current care pathway. Participants will be made aware at the time of consenting that the Noctura 400 Light Mask will not be available within the NHS at the end of the trial, but that the manufacturer intends for the device to be available to purchase privately

• Study Type: Interventional
• Enrollment (Actual): 252
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Plymouth, United Kingdom, PL6 8DH
    • Plymouth Hospitals NHS Trust
  • Berkshire
    • Reading, Berkshire, United Kingdom, RG1 5AN
      • Royal Berkshire NHS Foundation Trust
  • Cambridgeshire
    • Huntingdon, Cambridgeshire, United Kingdom, PE29 6NT
      • Hitchingbrooke Healthcare NHS Trust
    • Peterborough, Cambridgeshire, United Kingdom, PE3 9GZ
      • Peterborough and Stamford Hospitals NHS Foundation Trust
  • Cleveland
    • Middlesbrough, Cleveland, United Kingdom, TS4 3BW
      • South Tees Hospitals NHS Foundation Trust
  • Cornwall
    • Truro, Cornwall, United Kingdom, TR1 3LJ
      • Royal Cornwall Hospitals NHS Trust
  • Essex
    • Colchester, Essex, United Kingdom, CO4 5JL
      • Colchester Hospital University NHS Foundation Trust
  • Glouchestershire
    • Cheltenham, Glouchestershire, United Kingdom, GL53 7AG
      • Glouchestershire Hospitals NHS Foundation Trust
  • Hampshire
    • Basingstoke, Hampshire, United Kingdom, RG24 9NA
      • Basingstoke and North Hampshire NHS Foundation Trust
  • Lincolnshire
    • Scunthorpe, Lincolnshire, United Kingdom, DN15 7BH
      • North Lincolnshire and Goole NHS Trust
  • Norfolk
    • Great Yarmouth, Norfolk, United Kingdom, NR31 6LA
      • James Paget University Hospital NHS Foundation Trust
  • Norwich Norfolk
    • Colney, Norwich Norfolk, United Kingdom, NR4 7UY
      • Norfolk and Norwich University Hospitals Nhs Foundation Trust
  • Oxford Oxfordshire
    • Headington, Oxford Oxfordshire, United Kingdom, 0X3 9DU
      • Oxford Radcliffe Hospitals NHS Trust
  • Somerset
    • Yeovil, Somerset, United Kingdom, BA21 4AT
      • Yeovil District Hospital NHS Foundation Trust
  • Surrey
    • Chertsey, Surrey, United Kingdom, KT16 0PZ
      • Ashford & St Peters Hospitals NHS Foundation Trust
    • Guildford, Surrey, United Kingdom, GU2 7XX
      • Royal Surrey County Hospital
  • West Yorkshire
    • Wakefield, West Yorkshire, United Kingdom, WF1 4EE
      • Mid Yorkshire Hospitals NHS Trust
  • Wiltshire
    • Swindon, Wiltshire, United Kingdom, SN3 6BB
      • Great Western Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

i. Subjects of either sex aged 18 years or over. ii. Diagnosis of diabetes mellitus (type 1 or type 2). iii. Presence of clinically significant centre-involving macular oedema resultant from DR of ≥400µm (CST/CMT as measured by OCT, and is listed for ranibizumab therapy in the study eye.

Exclusion Criteria:

Any potential participant will be excluded if they have:

i. Received any previous anti-VEGF/steroid intravitreal injections in the study eye in the last 6 months.

ii. Presence of proliferative diabetic retinopathy (PDR) at screening.

iii. Significant systemic diseases know to affect visual function, other than diabetes (e.g. Parkinson's disease or Alzheimer's disease).

iv. History of relevant sleeping disorders/insomnia .

v. A condition that would preclude participation in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard Arm; Those receiving only their prescribed ranibizumab treatment only	Drug: Ranibizumab; Standard ranibizumab treatment only; Other Names: Those receiving their standard ranibizumab treatment only
Experimental: Intervention Arm; Noctura 400 Eye Mask in conjunction with their prescribed ranibizumab treatment.	Drug: Ranibizumab; Standard ranibizumab treatment only; Other Names: Those receiving their standard ranibizumab treatment only; Device: Noctura 400 Eye Mask; The intervention is the wearing of the eye mask; Other Names: Noctura400

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The number of intravitreal injections of ranibizumab required by each study eye at 48 weeks	48 Weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Mean difference from baseline Central sub-field thickness at 48 Weeks	48 Weeks
Mean difference from baseline visual acuity at 48 weeks.	48 Weeks
Mean difference in utility (quality of life).	Baseline, 12 and 48 weeks
Difference in the number of ranibizumab injections received by patients who have received at least three injections.	Between weeks 12 and 48
Change in Central sub-field thickness over time	12, 24,36 and 48 Weeks
Pattern of injections given over the period of 48 weeks in both arms.	48 weeks
Adverse events rates	48 months

Other Outcome Measures

Outcome Measure	Time Frame
Compliance of wearing the mask	48 weeks
Changes in sleep pattern.	48 months

Collaborators and Investigators

• Sponsor: PolyPhotonix Medical
• Investigators: Study Chair: Martin Holland, PolyPhotonix Medical; Principal Investigator: Ulrich Meyer-Bothling, Ashford & St Peters Hospitals NHS Trust

Publications and helpful links

Helpful Links

• Sponsor Website

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2014
• Primary Completion (Actual): August 1, 2023
• Study Completion (Actual): August 1, 2023

Study Registration Dates

• First Submitted: July 24, 2014
• First Submitted That Met QC Criteria: July 31, 2014
• First Posted (Estimated): August 4, 2014

Study Record Updates

• Last Update Posted (Actual): August 14, 2023
• Last Update Submitted That Met QC Criteria: August 9, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Diabetes; Diabetic retinopathy; Macular Oedema; Noctura
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Eye Diseases; Endocrine System Diseases; Diabetic Angiopathies; Diabetes Complications; Diabetes Mellitus; Retinal Degeneration; Macular Degeneration; Retinal Diseases; Diabetic Retinopathy; Macular Edema; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Ranibizumab
• Other Study ID Numbers: PPX-2014-004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO