A preliminary study comparing daily use of home-based hand-held Narrow Band UVB comb device versus biweekly hospital-based excimer light therapy in treatment of localized vitiligo

Not yet recruiting

• Conditions: Vitiligo,

• Registration Number: CTRI/2021/11/037885
• Lead Sponsor: AIIMS New Delhi

Brief Summary

INTRODUCTION

Vitiligois the commonest acquired de-pigmentary disorder of the skin affecting around1-2% of the world population without particular predilection for any age, raceor gender. People affected with vitiligo suffer from low self-esteem,psychological disturbance and diminished quality of life.[1,2]  For the non-surgical management of vitiligo various treatment modalities areavailable like corticosteroids, topical calcineurin inhibitors (TCIs) , vitaminD analogues (VDAs), antioxidants or phototherapy including psoralen ultravioletA (PUVA), narrow band ultraviolet B (NB-UVB) and 308-nm excimer laser[3].

Narrowband UVB therapy (311-312nm) delivered especially via whole body chambers, isstandard therapy for vitiligo. It has been shown to produce significantrepigmentation with good cosmetic matching with surrounding normal skin and hasan excellent safety profile including in children and pregnant women. Deviceshave also been developed to deliver ultraviolet light to the affected siteswithout exposing the entire body, which are referred to as targetedphototherapy. The excimer laser/light and hand-held NB UVB equipment are twosuch devices.Theexcimerlaser is a form of targeted NB-UVB that has been found to be more effectivethan whole chamber NB-UVB in treatment of both generalized and localizedvitiligo. [4-6]. Theexcimer laser containsa mixture of xenon and chloride gas that form unstable “excited dimersâ€. It releases 308 nm monochromatic UVB light. Themechanism of action of excimer laser in vitiligo is not completely understood,though it seems to stimulate melanocyte migration and proliferation due toincreased expression of Endothelin 1(ET1) [7]. The advantage of excimer laserover whole chamberNB-UVB isits targeted nature which reduces damage to the adjoining skin and decreasescumulative UV load, as it has been shownto achieve re-pigmentation faster witheasier access to difficult to reach areas.[4]Excimer laser can be combined with topical agents like tacrolimus 0.1% ointment[8,9], hydrocortisone 17-butyratecream[10], tetrahydrocurcuminoid cream[11], pimecrolimus 1%[12],khellin4%[13],calcipotriene[14] and tacalcitol ointment[15] for better results. The main drawbacks ofexcimer laser are its high cost, its availability only in tertiary caresettings and need for expertise in operation, hence the patient has to come tothe hospital twice or thrice a week, making it a logistical obstacle and alsocauses loss of wages both to the patient and his attendant. Excimer light at awavelength of 308nm is a non-collimated, non monochromatic slightly inexpensivealternative to the excimer laser, but has shown similar efficacy to excimerlaser.[35]

Homebased phototherapy is an alternative that can solve the aforementioneddrawbacks of excimer laser. Currently there are many devices to deliver NB-UVB,at home such as hand and foot units and hand held units.  Hand held NB-UVB units are cheap, portableand suitable for treatment of localized vitiligo. Their benefits includesignificant reduction in the number of hospital visits, cost benefit, sparingof uninvolved skin (targeted phototherapy) and ability to treat at early stageof vitiligo when intervention might be effective.It is a good option especiallyfor patients residing in inaccessible areas. Besides being handy, patients cantake the treatment at their convenient time leading to better compliance andadherence, hence increased response. This treatment can be combined with othermedical therapies too. The hand held devices consist of two Philips TL-9W/01NB-UVB lamps placed in a plastic casing that emit wavelength of 310-315nm (peak311) over 11x4 cm2 on which parallel arrays of toothed structure of 2 cm length(comb) are attached, which maintains a uniform distance between the device andvitiligo patches. The disadvantage of handheld NB-UVB  device seems to be its output, nearly half ofthat of the whole-body cabins with a faster rate of decay in irradiancenecessitating greater exposure time to the lesion to achieve a therapeuticfluence. So the equipment needs to be periodically calibrated [17].  Another limitation is its inability to beused in generalized vitiligo.

 Many patients are currently buying hand-heldNB-UVB units and using them at home and if they prove to be as effective andsafe as excimer devices,they will substantially reduce cost, number of hospitalvisits, long distance travel and also social and economic impact.

Hencethe present study is being undertaken to compare the efficacy and side-effectsof two targeted phototherapy devices i.e. hand-held NB-UVB comb device withexcimer light therapy in localized vitiligo.

 AIMS AND OBJECTIVES

To compare two targeted phototherapy devices i.e.home-based hand-held Narrow Band UVB comb device used daily versus biweeklyhospital- based excimer light therapy in treatment of localized vitiligo

RESEARCH QUESTION

Is home-based hand-held NB-UVB comb deviceat least as effective as Excimer light therapy in producing re-pigmentation inlocalized vitiligo?

HYPOTHESIS

Null hypothesis: Hand held NB-UVB therapyis inferior to excimer light therapy in treatment of localized vitiligo.

Alternate hypothesis: Hand held NB-UVBtherapy is not inferior to excimer light therapy in treatment of localizedvitiligo.

  AIMS AND OBJECTIVES

To compare two targeted phototherapy devices i.e.daily use of home-based hand-held Narrow Band UVB comb device versus biweeklyhospital-based excimer light therapy in treatment of localized vitiligo

 

1. Primary objective:

Comparison of percentage ofre-pigmentation of the representative vitiligo patch\* at the end of 4 months oftreatment between the two study groups.

2. Secondary objective:

• Comparison of percentage re-pigmentationin vitiligo between the two groups based on global assessment using Lund &Browder (L & B) score

• Assessment of re-pigmentation usingphotographic assessment (investigator global assessment)- assessment done bytwo independent dermatologists who are not part of the study.

·        Comparison of degree ofre-pigmentation at the end of four months in acral versus non acral sites

• Comparison of patients’ perspective ofre-pigmentation in vitiligo by Patient global assessment (PGA) score usingvisual analogue scale (VAS) from 0-10

• Change in dermatology life qualityindex, using Tjioe M et al questionnaire (annexure 3).

• Comparison of Quality of life (QOL)score between the 2 groups using VIS-22(a vitiligo-specific QoL instrument)(annexure 4).

 \*Representative vitiligo patch will be thelargest patch on the body excluding that on bony prominences, hands and feet ormucosae, and without predominant leukotrichia.

  MATERIALS AND METHODS

• **Studydesign**: Prospective, open, non-randomized study. The therapy to beadministered will be based on patients’preference.

·        **Number of patients:**At least 20 patients will be included in each group

·        **SAMPLE SIZE CALCULATION:**Sample size for the study has been computed to compare percentage ofre-pigmentation at 4 months of follow up in both the groups by parallel non-inferior trial based on following assumption: -

1. Non – inferiority margin 5%

2. Observed or expected difference in re-pigmentation is zero

3. Pull standard deviation 0.05 i.e. effect size is 0.1

4. Power of the study 90%

5. Confidence level 95%

Based on above assumption the required number ofpatients in each group will be 18. Taking in consideration for the loss tofollow-up, we will take at least 20 patients in each group.

• **Dosageof therapy:**

**GROUP A:-(hand-held NB-UVB comb device)-**dosage of 500mJ/cm2 once daily will be administered to allvitiligo patches.

The exposure time for each patch will becalculated by recording the irradiance of the lamps (in mW/cm2)using a UV tester (Waldmann UV tester, Germany) and keeping the fluence to bedelivered as 500 mJ/cm2 using the formula-

Time of exposure (seconds) = Dose in mJ/cm2/Irradiance in mW/cm2

The irradiance of each device will bemeasured at 45sec, 1min, 2min, 3min, 4min, and 5min.

The patients will be explained in detailregarding the use of hand held NB-UVB comb device and will be provided withwritten details regarding the time of exposure on each patch. The patients willtake this therapy every day at home. After switching the lamp on for 45seconds, they will start exposing the patches to NB-UVB light. The first patchto be exposed would be the representative patch, followed by sequentialexposure of next 2 patches. The handheld comb device will be switched off for 5minutes and subsequently next 3 patches will be exposed and then device will beswitched off for 5 minutes. This procedure will be repeated for rest of thepatches in similar manner once daily.

If the vitiligo patch is on face or in anarea that is inaccessible, participants will be advised to seek help fromsomeone else to administer the treatment. All devices will be supplied with UVprotective goggles (for both the participants and their helper as required),which will be worn at all times during use. In addition, participants willreceive training on management of side effects and adherence to treatment schedule.The patient would be advised for adequate photoprotection on the exposed sitei.e. both physical and chemical.

**GROUP B: - (excimer light therapy) –**dosage will be based on minimal erythema dose (MED)for each site. MEDwill be based on those calculated for each site based on previous literature.MED for each site will be taken as--:

1. Perioral, peri ocular area: 100 mJ/cm2

2. Rest of the face and neck: 150 mJ/cm2

3. Upper limb: 200 mJ/cm2

4. Trunk: 200mJ/cm2

5. Lower limb: 300mJ/cm2

6. Elbow: 300mJ/cm2

7. Knee: 350mJ/cm2

8. Hand: 250mJ/cm2

9. Foot: 400mJ/cm2

Each vitiligo patch will be exposed tostarting dose of 50 mJ/cm2 lower than the MED, which will be increased by 10%every session to reach patient’s MED i.e the minimal dose sufficient to producebarely perceptible well-defined erythema in the vitiliginous area after 24hours of application.If erythema remains for ≤48 hours, the dose willbe keptthe same. If erythema persists for more than 48 hours, the dose will be reducedto the last well tolerated one. This therapy will be hospital based, twice aweek on non-consecutive days.

·        **Duration of treatment:** 4 months

·        **Study Setting:** The study will be conducted in the outpatient department andPhototherapy clinic of the Department of Dermatology and Venereology at AllIndia Institute of Medical Sciences, New Delhi

• **Ethicalconsiderations:** Approval will be taken from the Institutional EthicsCommittee for Post Graduate Research of the All India Institute of MedicalSciences, New Delhi before starting this study.

·        Approval of CTRI willalso be taken before starting the study

• **Investigationspecifically related to projects:** None

• **Inclusion criteria**:

✓ Consecutive patients of localized vitiligo i.e. ≤2%BSA or ≤10 patches.

✓ Patients ≥18 years of age.

✓ Patients who have not taken any topical therapy inlast 2 weeks or systemic therapy in last 4 weeks

✓ Patients giving consent for using hand heldNB-UVB/excimer light

• **Exclusion criteria**:

✓ Patients with rapidly spreading vitiligoi.e.development of ≥ 5 new lesions in the past 1 month or ≥ 15 lesions in thepast 3 months.

✓ Patients with recalcitrant forms of vitiligo i.e.,lip-tip vitiligo, segmental vitiligo, genital vitiligo and with predominantleukotrichia on patches.

✓ Patients with concomitant photo-aggravateddermatoses.

✓ Patients who are unable to adhere to instructions onuse of the hand-held NB-UVB comb device or maintain it or patients unable tovisit the hospital for excimer light therapy

 Â·       **Efficacy Parameters for assessment**

 1.     Primary efficacyparameter:-

Comparison of percentage re-pigmentationof the representative vitiligo patch at the end of 4 months of treatmentbetween the two study groups.

2.     Secondary parameters: -

• Percentage re-pigmentation in vitiligobased on global assessment using Lund & Browder score

• Assessment of re-pigmentation usingphotographic assessment (Investigator Global Assessment -IGA)-

• Patient global assessment (PGA) scoreusing visual analogue scale (VAS) from 0-10

• Change in dermatology life qualityindex, using Tjioe M et al questionnaire

• Quality of life (QOL) score using VIS-22(a vitiligo-specific QoL instrument)

• Comparison of side-effects such aserythema, edema, pruritus, pain, vesiculation

Patients fulfilling inclusion criteriawill be enrolled in either of the two groups in a non-randomized manner, basedon patients’ convenience. A detailed history followed by a thorough generalphysical, dermatological and systemic examination will be undertaken as perproforma attached. The representative vitiligo patch will be selected andgraphical assessment will be done to measure the area of involvement. Atransparency sheet will be used to delineate the area involved, which will besubsequently used to calculate the exact area involved using a standard graphpaper. The representative patch will be marked as 1(one) and rest of thepatches will be numbered in a sequence. These will be depicted and numbered ona body chart made in the proforma and one proforma will be given to patient.Baseline disease severity will be assessed using following parameters:

1. Area of involvement by vitiligo will becalculated using Lund and Browder (L & B) chart (Annexure 2)

2. Patient global assessment (PGA) on ascale of 0–10 (to assess degree of improvement on a VAS scale from 0-10, 0being the baseline disease and 10 indicating complete re-pigmentation)

3. Investigator global assessment (IGA;done by two independent dermatologists, on a scale of −1 to 5, where:−1 =worsening, 0 = no change, 1 = <25% re-pigmentation, 2 = 26–50%, 3 = 51–75%,4 = 76–90% and 5 = 91–100% re-pigmentation) comparing pre- and post-treatmentphotographs.

4. Quality of life (QOL) score (usingTjioe M et al. questionnaire which compares QOL before and after phototherapyand rates it on a scale of −28 to 28) (Annexure 3)

5. Quality of life (QOL) score usingVIS-22(vitiligo- specific QoL instrument). (Annexure 4)

 6. Recording of adverse events-Participants will be instructed to record adverse events in their treatmentdiaries and to contact us if they experience side effects of concern. Fortreatment-related side effects, or drug-induced photosensitivity, we willprovide telephonic advice

**Follow up period**: 0, 2, 4, 8, 12, 16weeks

• Graphical assessment, L & B scoring,IGA, PGA (at each visit)

• Quality of life assessment using scoreby Tjioe M et al and using VIS-22(a vitiligo- specific QoL instrument)(baseline and end of treatment)

·        Assessment ofside-effects in the 2 groups (at each visit)

Detailed Description

Not available

Study Timeline

• Last Update Posted: 2021-09-11
• Study Start: 2021-11-11

Recruitment & Eligibility

• Status: Not Yet Recruiting
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

• Consecutive patients of localized vitiligo i.e. ≤2% BSA or ≤10 patches.
• Patients ≥18 years of age.
• Patients who have not taken any topical therapy in last 2 weeks or systemic therapy in last 4 weeks 4.
• Patients giving consent for using hand held NB-UVB/excimer light.

Exclusion Criteria

• Patients with rapidly spreading vitiligo i.e.development of ≥ 5 new lesions in the past 1 month or ≥ 15 lesions in the past 3 months.
• Patients with recalcitrant forms of vitiligo i.e., lip-tip vitiligo, segmental vitiligo, genital vitiligo and with predominant leukotrichia on patches.
• Patients with concomitant photo-aggravated dermatoses.
• Patients who are unable to adhere to instructions on use of the hand-held NB-UVB comb device or maintain it or patients unable to visit the hospital for excimer light therapy.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Comparison of percentage re-pigmentation of the representative vitiligo patch	4 months

Secondary Outcome Measures

Name	Time	Method
Comparison of percentage re-pigmentation in vitiligo between the two groups based on global assessment using Lund & Browder (L & B) score	4 months
Assessment of re-pigmentation using photographic assessment (investigator global assessment)- assessment done by two independent dermatologists who are not part of the study	4 months
Comparison of patients’ perspective of re-pigmentation in vitiligo by Patient global assessment (PGA) score using visual analogue scale (VAS) from 0-10	4 months
Comparison of degree of re-pigmentation at the end of four months in acral versus non acral sites	4 months
Change in dermatology life quality index, using Tjioe M et al questionnaire	4 months
Comparison of Quality of life (QOL) score between the 2 groups using VIS-22(a vitiligo-specific QoL instrument)	4 months

Trial Locations

Locations (1)

AIIMS, New Delhi; 🇮🇳 South, DELHI, India

AIIMS, New Delhi

🇮🇳South, DELHI, India

Dr Iftekhar Khan

Principal investigator

iftekhar1995@gmail.com