Condition category
Skin and Connective Tissue Diseases
Date applied
12/06/2014
Date assigned
12/06/2014
Last edited
06/01/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Erosive lichen planus affecting the vulval area causes painful ulcers which last for a long time and are difficult to treat. Very little research has taken place into treatments for erosive lichen planus affecting the female external genital area (vulva) and it is not clear which is the best treatment for people who have severe disease. To find that out, this study will compare three most commonly used tablets against an ointment and a short course of steroid tablets. The tablets we are testing will fine tune or dampen the body's immune system. This is because an overactive immune system is thought to be the cause of erosive lichen planus.

Who can participate?
Adult patients with vulval erosive lichen planus that has not responded well to standard treatment with creams and ointments.

What does the study involve?
Participants will randomly be asked to take one of the four treatments, although some of the treatments require additional tablets to be taken alongside them to prevent side effects. Participants will be able to use a moisturising cream and strong steroid ointment alongside the tablet treatment. They will be given the trial treatment for 6 months initially, after which time it can be continued if it has been effective. If it has not been effective, treatment can be changed. This is a decision that will be made between the participant and their hospital consultant.

What are the possible benefits and risks of participating?
There are no guaranteed direct benefits because we cannot be sure that the medications will help you but the information we get from this study may help to guide doctors in how patients should be treated in the future. Because this study is comparing four commonly used treatments and the study is designed to mimic normal care, there are no additional risks to participants in taking part in this study. The care that participants will receive will be very similar to the care that they would receive if they were not taking part in the study. Participants will be closely monitored as part of their usual care.

Where is the study run from?
The study is run from certain hospital departments in the UK that specialize in treating vulval skin disorders.

When is the study starting and how long is it expected to run for?
The study runs from June 2014 until April 2016. Each person will take part in the study for 12 months. July 2015 is the end of recruitment phase.

Who is funding the study?
The National Institute for Health Research (NIHR) (UK).

Who is the main contact?
Dr Rosalind Simpson
helpstudy@nottingham.ac.uk

Trial website

http://www.nottingham.ac.uk/research/groups/cebd/projects/help-trial/index.aspx

Contact information

Type

Scientific

Primary contact

Dr Rosalind Simpson

ORCID ID

Contact details

Centre of Evidence Based Dermatology
Kings Meadow Campus
Lenton Lane
Nottingham
NG7 2NR
United Kingdom
-
rosalind.simpson@nottingham.ac.uk

Additional identifiers

EudraCT number

2014-000547-32

ClinicalTrials.gov number

Protocol/serial number

16788

Study information

Scientific title

A randomised controlled trial of adjunctive systemic therapy for vulval Erosive Lichen Planus

Acronym

hELP

Study hypothesis

To test whether hydroxychloroquine, methotrexate or mycophenolate mofetil are better than standard care with topical clobetasol propionate 0.05% plus a short course of oral prednisolone in patients with vulval erosive lichen planus that has been refractory to first-line therapy.

Ethics approval

NRES Committee Yorkshire and The Humber - Sheffield, 14/04/2014, 14/YH/0046

Study design

Randomised; Interventional; Design type: Not specified

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

http://www.nottingham.ac.uk/research/groups/cebd/documents/researchdocs/help-pis-final-v2-0-31-03-14.pdf

Condition

Topic: Dermatology; Subtopic: Skin (all Subtopics); Disease: Dermatology

Intervention

Intervention:
Participants will be randomised to receive one of the three active interventions or to receive the comparator, clobetasol propionate 0.05% plus oral prednisolone, which is standard care:

Comparators
Hydroxychloroquine, oral administration, up to 6.5 mg/kg lean body weight, maximum dose of 200 mg BD (in conjunction with topical clobetasol propionate 0.05%). Treatment duration 6 months.
Methotrexate, oral administration, dose commencing at 5 mg/week and gradually increase as per protocol according to response to a maximum of 25 mg/week (in conjunction with topical clobetasol propionate 0.05%. Treatment duration 6 months.
Mycophenolate mofetil, oral administration, dose commence at 500 mg OD and gradually increase as per protocol according to response to a maximum dose of 1.5 g BD (in conjunction with topical clobetasol propionate 0.05%) Treatment duration 6 months.

Standard Care
Clobetasol propionate 0.05% (standard care), topical application, once daily for 1 month and regimen reduced according to response. Maximum 60 g over 6 months (British Association of Dermatologists guidance for the treatment of lichen sclerosus).
Oral prednisolone: an initial 4-week course on a reducing regimen of 20 mg OD for 1 week, reducing by 5 mg per week.

Intervention type

Drug

Phase

Not Applicable

Drug names

Hydroxychloroquine, methotrexate, mycophenolate mofetil, clobetasol propionate, prednisolone

Primary outcome measures

Current primary outcome measures as of 08/12/2014:
Proportion of participants achieving treatment success at 6 months; Treatment should be classed as successful if both criteria and are met:
1. Patient Global Assessment score of 0 or 1 on a 4-point scale
2. Assessment of improvement from baseline judged by clinical images

Previous primary outcome measures:
Proportion of participants achieving treatment success at 6 months; Treatment should be classed as successful if both criteria and are met:
1. Patient Global Assessment score of 0 or 1 on a 4-point scale
2. Investigator Global Assessment of improvement from baseline judged by clinical images

Secondary outcome measures

Current secondary outcome measures as of 08/12/2014:
1. Reduction in pain/soreness
2. Global assessment of disease assessed through:
2.1. Patient Global Assessment
2.2. Investigator Global Assessment by treating clinician
2.3. Assessment by blinded assessor using clinical images
3. Assessment of other affected mucosal sites by treating clinician
4. Psychological assessment using the Hospital Anxiety and Depression Scale
5. Assessment of sexual function
6. Health-related quality of life – using
6.1. ‘Skindex-29’
6.2. ‘Short Form 36’
7. Days of topical steroid use during treatment period
8. Treatment satisfaction – assessed as overall satisfaction plus number of participants continuing treatment post the primary endpoint
9. Adverse events (AEs) reported during the study, and discontinuation of medications due to AEs
10. Average cost of intervention in each treatment group per participant

Previous secondary outcome measures:
1. Reduction in pain/soreness
2. Global assessment of disease assessed through:
2.1. Patient Global Assessment
2.2. Investigator Global Assessment by treating clinician
2.3. Investigator Global Assessment by blinded assessor using clinical images
3. Assessment of other affected mucosal sites by treating clinician
4. Psychological assessment using the Hospital Anxiety and Depression Scale
5. Assessment of sexual function
6. Health-related quality of life –using
6.1. ‘Skindex-29’
6.2. ‘Short Form 36’
7. Days of topical steroid use during treatment period
8. Treatment satisfaction – assessed as overall satisfaction plus number of participants continuing treatment post the primary endpoint
9. Adverse events (AEs) reported during the study, and discontinuation of medications due to AEs
10. Average cost of intervention in each treatment group per participant

Overall trial start date

01/06/2014

Overall trial end date

30/04/2016

Reason abandoned

Eligibility

Participant inclusion criteria

Current inclusion criteria as of 08/12/2014:
1. Clinical diagnosis of erosive lichen planus affecting the vulvovaginal region (ELPV)
2. Documented histological examination in the patient’s history that excludes malignant/pre-malignant disease. Biopsy should be repeated if clinically indicated prior to consideration of systemic therapy
3. Inadequate disease control despite first-line therapy with clobetasol propionate 0.05% for at least 3 months
4. Moderate or severe disease on Investigator Global Assessment
5. Microbiological swabs negative, or result that is not clinically relevant, at study entry
6. Willing and capable of giving informed consent
7. Willing to have clinical images taken
8. Female aged 18 years or over
9. Use of effective contraceptive methods in females of childbearing age for the duration of treatment
10. For participants receiving methotrexate to use effective contraceptive methods until 6 months after the end of treatment

Previous inclusion criteria:
1. Clinical diagnosis of erosive lichen planus affecting the vulva
2. Histological examination within the past 12 months to exclude alternative diagnoses
3. Inadequate control despite first-line therapy with clobetasol propionate 0.05%
4. Disease severity of moderate-severe on Investigator Global Assessment
5. Negative microbiological swabs at study entry
6. Willing and capable of giving informed consent
7. Willing to have clinical images taken
8. Age >18 years (there is no upper age limit)
9. Use of effective contraceptive methods in females of childbearing age

Target Gender: Female; Upper Age Limit 99 years ; Lower Age Limit 18 years

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

Planned Sample Size: 96; UK Sample Size: 96

Participant exclusion criteria

Current exclusion criteria as of 08/12/2014:
1. Cases of lichen sclerosus/lichen planus overlap
2. Received one or more of the trial drugs within the last one month (excluding clobetasol propionate 0.05%)
3. Previous/current diagnosis of malignant disease (skin or internal)
4. History of or current diagnosis of pre-malignant vulval skin or cervical disease
5. Receiving concurrent medications that would preclude the use of any of the trial medications in normal practice
6. History of clinically significant renal or liver impairment or other pre-existing medical conditions that would preclude the use of any of the trial medications in normal practice
7. Administration of a live vaccine (BCG, Measles, Mumps, Rubella, Yellow Fever, Oral Polio, Oral Typhoid) within the last 2 weeks
8. Pregnancy or breast-feeding
9. Known allergy to any of the trial medications

Previous exclusion criteria:
1. Cases of lichen sclerosus/lichen planus overlap
2. Patients taking beta blockers or non-steroidal anti-inflammatory medications
3. Received one or more of the trial drugs within the last month (excluding clobetasol propionate 0.05%)
4. Previous/current diagnosis of malignant disease (skin or internal)
5. Pre-malignant vulval skin or cervical disease
6. Receiving concurrent medications that would preclude the use of any of the trial medications in normal practice
7. History of clinically significant renal or liver impairment or other pre-existing medical conditions that would preclude the use of any of the trial medications in normal practice
8. Administration of a live vaccine (BCG, measles, mumps, rubella, yellow fever, oral polio, oral typhoid) within the last 2 weeks
9. Pregnancy or breastfeeding
10. Known sensitivity to any of the trial medications

Recruitment start date

15/08/2014

Recruitment end date

31/07/2015

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Nottingham University Hospitals NHS Trust
Nottingham City Hospital
Nottingham
NG5 1PB
United Kingdom

Trial participating centre

Grampian Health Board
Aberdeen Royal Infirmary
Aberdeen
AB25 7ZD
United Kingdom

Trial participating centre

East Lancashire Hospitals NHS Trust
Royal Blackburn Hospital
Blackburn
BB2 3HH
United Kingdom

Trial participating centre

Bradford Teaching Hospitals NHS Trust
St Luke's Hospital
Bradford
BD5 0NA
United Kingdom

Trial participating centre

Cardiff and Vale University Local Health Board
University Hospital of Wales
Cardiff
CF14 4XW
United Kingdom

Trial participating centre

Leeds Teaching Hospital NHS Trust
Chapel Allerton Hospital
Leeds
LS7 4SA
United Kingdom

Trial participating centre

Royal Liverpool and Broadgreen University Hospitals NHS Trust
Broadgreen Hospital
Liverpool
L14 3LB
United Kingdom

Trial participating centre

Barts Health NHS Trust
Whipp’s Cross Hospital
London
E11 1NR
United Kingdom

Trial participating centre

Central Manchester University Hospitals NHS Foundation Trust
St Mary’s Hospital
Manchester
M13 9WL
United Kingdom

Trial participating centre

Cambridge University Hospitals NHS Foundation Trust
Addenbrookes Hospital
Cambridge
CB2 0QQ
United Kingdom

Trial participating centre

Tayside Health Board, Ninewells Hospital and Medical School
Dundee
DD1 9SY
United Kingdom

Trial participating centre

Salford Royal NHS Foundation Trust
Salford Royal Hospital
Salford
M6 8HD
United Kingdom

Sponsor information

Organisation

University of Nottingham (UK)

Sponsor details

Division of Primary Care
Graduate Medical School
London
NG7 2NR
United Kingdom

Sponsor type

University/education

Website

Funders

Funder type

Government

Funder name

NIHR Doctoral Research Fellowship; Grant Codes: DRF-2012-05-166

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

To be confirmed at a later date

Intention to publish date

Participant level data

Not expected to be available

Results - basic reporting

Publication summary

2016 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/26729245

Publication citations

Additional files

Editorial Notes