Title: Home Interventions and Light therapy for the treatment of vitiligo (HI-Light Vitiligo Trial)
Funder: Department of Health and Social Care

Abstract: DESIGN: 3-arm, parallel group, double-blind RCT. Treatment will be for 9 months, with follow-up for a further 12 months after end of treatment (21 months in total). SETTING: Participants will be recruited in up to 16 UK hospitals. Treatment will be initiated in secondary care with self-treatment at home. Potential participants will be identified in secondary care, primary care and through direct advertising. TARGET POPULATION: Children (aged 5 years and over) and adults, with non-segmental vitiligo affecting less than 10% of body surface area, and at least one lesion that has appeared or has spread in the last 12 months. HEALTH TECHNOLOGIES: Hand-held narrow-band ultra-violet light therapy (NB-UVB) and potent topical corticosteroids will be compared with each other, and combination therapy will be compared to topical corticosteroids alone. Participants will be allocated to three groups: NB-UVB light therapy plus placebo ointment; placebo NB-UVB light therapy plus potent topical corticosteroid ointment; or NB-UVB light therapy plus potent topical corticosteroid ointment. MEASUREMENT OF COSTS & OUTCOMES: Primary outcome: Participant-reported treatment success at a target patch of vitiligo at 9 months (measured by how noticeable the vitiligo is compared to before treatment. Secondary outcomes: 1. Investigator-assessed onset of treatment response 2. Participant -reported treatment success for different body regions 3. Percentage repigmentation at 3, 6 and 9 months 4. Quality of life at end of treatment (9 months) and end of follow-up (21 months), using VitiQol, Skindex 29 and EQ-5D for adults, and CHU 9D for children 5. Time burden of treatment 6. Maintenance of gained repigmentation during follow-up phase Within trial cost-effectiveness analysis will also be conducted from an NHS perspective (primary) and a family perspective (secondary) SAMPLE SIZE: Assuming that 15% of participants allocated to receive topical corticosteroid (plus dummy light therapy) achieve treatment success as defined by the primary outcome, 372 participants are required to detect an absolute difference of 20%, with 2.5% two-sided alpha and 90% power. Allowing for 15% loss to follow-up, it was planned that a total of 440 participants would be recruited. Following a sample size review carried out by the Data Monitoring Committee in December 2016 the sample size was increased to 516 participants. PATIENT & PUBLIC INVOLVEMENT: This trial has been developed in response to a James Lind Alliance Priority Setting Partnership that identified this as an important topic for further research. The Priority Setting Partnership was also used to identify the most important outcome measures for use in vitiligo trials, and these results have been used to guide our choice of outcomes. A patient with vitiligo has been actively involved in the trial development group (as well as the Cochrane systematic review and pilot trial), and is a co-applicant on the grant. Feedback from participants in our pilot trial has been used to inform the data collection tools, training materials and choice of devices to be used. TIMETABLE: Based on our pilot RCT recruitment rates, we estimate that 3-5 participants will be randomised per centre per month. Duration of trial: 4 years 3 months. Approvals and set-up (6 months), recruitment (18 months), treatment (9 months), follow-up (12 months), analysis and write-up (6 months).

Lay abstract: Vitiligo is a common skin disorder affecting about 1% of the world’s population, regardless of age, sex or skin colour. Vitiligo causes white patches on the skin, which can spread to cover large areas of the body. It is more noticeable on dark or tanned skin, causing people with vitiligo to be stigmatised in some communities. Vitiligo can be sporadic with long periods of inactivity, spread slowly or progress rapidly causing feelings of panic, depression and despair. Although vitiligo is not fatal, it can have a devastating effect on the quality of life of those who have it, particularly if it affects visible sites such as the face and hands. Children can experience teasing and bullying as a result of having the disease and many adults report a lack of confidence, poor self esteem and an inability to form relationships. Current treatments for vitiligo are limited. They seldom restore natural skin colour to all the white patches and do not prevent a recurrence of the disease. In the early stages of the disease the use of corticosteroid creams or other ointments can sometimes be successful. GPs are often unaware of the psycho-social effects of vitiligo and in the absence of treatments specifically licensed for vitiligo may offer no help to the patient apart from special make-up to cover up the white patches. Light treatment prescribed for extensive vitiligo can work for some, but requires prolonged and frequent visits to hospital. The justification for this project comes from two sources. The first is a Cochrane review published in 2010 which assessed 57 published trials of treatments for vitiligo, but did not find sufficient evidence to recommend any treatment due to the poor quality of the studies. However, there was some evidence to suggest that a better result can be achieved by using a combination of treatments, including some form of light. The second is a prioritisation project conducted in 2011 in partnership with the James Lind Alliance involving both clinicians and patients. This exercise identified 10 important questions for research, including: a) Which is more effective, steroid creams or light therapy? b) How effective is narrow band ultra-violet light therapy (NB-UVB) when combined with creams or ointments? This study will involve 516 people with vitiligo including children aged 5 years and over and adults. By giving people with vitiligo the opportunity to treat themselves or their children at home the researchers hope to avoid the inconvenience of having to attend hospital two or three times a week for light therapy. There is also the possibility that early treatment of small vitiligo areas could mean shorter treatment periods and better treatment response. People with active vitiligo (new or spreading patches) that affects less than 10% of their body will be invited to take part in the study, as these are the people who are most likley to benefit from the treatments being compared. Participants will be randomly allocated to receive either light therapy plus a placebo (dummy) ointment, or a steroid ointment plus placebo (dummy) light therapy, or a combination of steroid ointment and light therapy. The light therapy will be delivered using a small hand held light therapy device used three times a week, and the ointment applied to the skin once daily on a 'one week on, one week off' basis. The light therapy device is easy to use and has a spacer to avoid the light getting too close to the skin. There are also safety goggles to protect the eyes from the light. The participants in the study will be interviewed beforehand, given a leaflet to explain the study, and shown a training video on how to use the treatments. They will be asked to use a diary to record their treatment sessions and any side effects. They will be supervised by a research nurse, and will be able to contact the trial team should there be any problems with the treatment. One possible side effect of the light therapy is burns, but clear instructions as to how to distinguish burns from just a reddening of the skin will be given and treatment can be adjusted accordingly. Participants will receive treatment for 9 months and response will be assessed in clinic every 3 months. At the end of the treatment period participants will be followed-up for a further 12 months so that the long-term response to treatment can be checked. Each participant will be enrolled for a total of 21 months. The study will take place in approximately 16 hospitals in the UK. A recently completed pilot study has examined the use of the hand held NB-UVB light therapy devices and recruited participants from Nottingham and Leicester. The pilot study has provided useful information for the main trial. The main trial will be co-ordinated from the Nottingham Clinical Trials Unit in collaboration with the Centre of Evidence Based Dermatology, which has a good track record of conducting and completing clinical trials in skin diseases. The trial has been designed to reflect what might happen in normal clinical practice, so the burden of participation in the study is low and the risks are small. Both of the compared treatments are recommended for the treatment of vitiligo and are appropriate for both children and adults. For children, informed consent will be taken from the parents / legal guardians, but the wishes of the child will be respected. Age-appropriate study information will be provided. After many years when there was little research into vitiligo, our knowledge and understanding of this disease is growing. This trial could add to the choice of treatments available for people with vitiligo, many of whom receive no treatment at all. Should the trial prove a success, it could make a big difference to the lives of many people who have not had much help for what has often been considered a trivial, cosmetic condition.

Research activity codes: 6.1 PHARMACEUTICALS;6.3 MEDICAL DEVICES
Health categories: SKIN