PEARLS Trial

Proactive against reactive therapy for the prevention of lichen sclerosus exacerbation and progression of disease – a pragmatic, parallel group randomised controlled trial with embedded economic evaluation and process evaluation

Abbreviations: LS – Lichen Sclerosus; TCS – Topical Corticosteroid; SCC - Squamous Cell Carcinoma; PIC - Participant Identification Centre

  

PEARLS study is open to recruitment

PEARLS has successfully completed its 6-month pilot phase, recruiting 74 patients across 14 sites since the first site was opened in April 2024.

Congratulations to the sites for all their hard work.

 

 

No. of participants recruited: 121

About PEARLS

Vulval Lichen Sclerosus (LS) is a chronic inflammatory condition, with incidence peaking in childhood and post-menopause. Reported prevalence is up to 3%, affecting around 1 million women in the UK. Inflammation causes whitening of vulval tissue, bleeding under the skin, texture change and cuts. Patients report itching, pain (particularly during sex) and discomfort in daily activities. Untreated LS can cause progressive loss of vulval architecture. Scarring may occur early in the disease and is irreversible without surgery. LS persisting beyond puberty may prevent normal vulval anatomical development.

LS is associated with risk of vulval intraepithelial neoplasia and vulval Squamous Cell Cancer. Rates of vulval SCC with LS are 20 times higher than in the general population with higher mortality than vulval SCC without LS.

The impact of LS is considerable due to the intimate and ‘taboo’ nature of the problem. LS affects psycho-social and sexual functioning and leads to embarrassment, isolation and relationship breakdown/difficulty in forming new relationships.

Watch Dr Rosalind Simpson, the study Chief Investigator, speaking in this video about lichen sclerosus.

Who is organising and funding this study?

The trial is being organised by the University of Nottingham (the Sponsor) and coordinated centrally by the Nottingham Clinical Trials Unit (NCTU).

This study is funded by National Institute for Health and Care Research (NIHR) Heath Technology Assessment (HTA) Ref: NIHR135121.

Chief Investigator: Dr Rosalind Simpson, Associate Professor and Consultant Dermatologist

Link to PEARLS NIHR Research Award

UoN logo 24/05/2023  NIHR-White-Background NCTU-white-background 

 

 

Overview

We are conducting a 2-arm, parallel-group, individually randomised, unblinded, multicentre, superiority trial with an internal pilot phase.

The trial aims to recruit 400 female participants (aged 5 years and older) over a 12 month period. Each participant will be followed up for 24 months. 

The trial will compare a topical corticosteroid (TCS) applied on two non-consecutive days per week, even in absence of symptoms, (‘proactive treatment’) versus TCS as required to use only to treat a flare until symptoms resolve (‘reactive treatment’), for 12 months. The treatments will not be blinded. Choice of potent/superpotent TCS preparation is tailored to the patient as not all patients can tolerate a specific formulation. 

Trial Intervention

Intervention: Potent or superpotent Topical Corticosteroid (TCS) used for two non-consecutive days per week even in absence of symptoms (‘proactive treatment’).

Comparator: treatmeant of flare as required with potent or superpotent TCS, i.e. ‘reactive treatment’, daily until flare resolves (typically up to 7 days).

Trial sites

The trial participants will be recruited from across the UK.  The trial plans to open at least 15 recruiting centres (sites).  Click on a pin on the map for details of selected trial sites.

List of Currently Open Trial Sites                                                                                                    
Site Date opened
Nottingham University Hospitals NHS Trust 10/04/2024
South Tees Hospital NHS Trust - James Cook 17/04/2024
Liverpool Women's NHS Foundation Trust  29/04/2024
Surrey and Sussex Healthcare NHS Trust 10/05/2024
Gateshead Health NHS Foundation Trust  15/05/2024
Shrewsbury and Telford NHS Trust  20/05/2024
Leicester - University Hospitals Leicester 24/05/2024
Oxford University Hospitals NHS Foundation trust 20/06/2024
Manchester University NHS Foundation Trust  27/06/2024
Barts Health NHS Trust 01/07/2024
Oxleas NHS Foundation Trust 08/07/2024
Liverpool Axess - Royal Liverpool University Hospitals NHS Foundation Trust 02/08/2024
Blackburn - East Lancashire Hospitals NHS Trust 05/08/2024
Derby - University Hospitals Derby and Burton 05/08/2024
Aberdeen - NHS Grampian 23/10/2024
Norwich - Norfolk and Norwich University Hospitals NHS Foundation Trust 11/11/2024
 

 

Participant Identification Centres (PICs) will be set up at GP practices where potential participants will be identified with pre-defined eligibility criteria. Initially only PICs sites that are in the proximity of three sites, Nottingham University Hospital, Liverpool Womens' Hospital and Liverpool University Hospitals, will be in operation. Patients will also be able to self-refer to these three sites

 

Inclusion and exclusion criteria

Inclusion criteria

  1. Clinical or biopsy confirmed diagnosis of vulval LS
  2. Currently controlled disease (asymptomatic with minimal clinical evidence of active disease) at baseline
  3. Age ≥5 years
  4. Able to give consent/child assent plus parental consent

Exclusion criteria

    1. Previous vulval intraepithelial neoplasia (VIN) or vulval squamous cell carcinoma (SCC)
    2. Contraindications to topical steroids
    3. Concomitant use of other topical anti-inflammatory vulval treatments
    4. Using systemic immunosuppressants (for any indication)
    5. Using systemic treatment for LS
    6. Patients with surgical alteration of vulval skin as part of gender reaffirming surgery, or patients not born with a vulva
    7. Pregnant and breastfeeding women
 

 

Trial outcomes

For the purposes of recording outcomes, age categories are divided into:

  1. Children (5 - <12 years)
  2. Adolescents (12 - <16 years)
  3. Adults (16 years and over)

Primary outcome

Number of flares over 12 months. Flare is defined as worsening of symptoms1 requiring increased application of TCSs.

Secondary outcomes

Clinical effectiveness

  • Progression of scarring assessed by blinded assessor at 12 and 24 months by comparing post randomisation to baseline photographs (if participant consented), and assessed clinically: Vulvar Architectural Severity Scale (VASS) at 12 and 24 months post randomisation.
    • Adults: scarring worsened (yes/no)
    • Children and adolescents: failure of normal vulval development (clinical assessment) and/or evidence of scarring (yes/no).
  • Time to first flare.
  • Global clinical severity assessment of LS (5-point ordinal scale) at 3, 6, 12, 18 & 24 months, plus assessed by blinded assessor at 12 and 24 months.
  • Condition specific QoL at 3, 6, 12, 18 & 24 months using:
    • Vulvar Quality Life Index (VQLI) (adults)
    • Children’s Dermatology Life Quality Index (CDLQI) (adolescents and children).
  • Sexual function (adults only) using Female Sexual Function Index at 12 & 24 Months.

Safety

  • Development of vulval intraepithelial neoplasia or vulval squamous cell carcinoma at 24 months.
  • Targeted adverse events e.g. stinging, skin thinning measured by patient reported symptoms and clinical examination from randomisation over 24 months.

Treatment acceptability and potential barriers/facilitators to treatment

  • Acceptability of treatment strategy at 12 and 24 months using a Likert scale.
  • Adherence to treatment at 3, 6, 12, 18 & 24 months.
  • Qualitative interview sub-study at 12 months.

Cost-effectiveness

  • Generic utility instrument to measure QoL at 3, 6, 12, 18 & 24 months with EQ-5D-5L (adolescents and adults) and CHU-9 (children).
  • Resource use including prescription, direct and indirect healthcare and out-of-pocket costs associated with LS at 3, 6, 12, 18 and 24 months.
 

 

Information for Participants

The information here is to help you understand why the research is being carried out and what it will involve for you if you decide to take part. Please ask us if you would like to have more information, or if there is anything that is unclear to you.

Watch this short video about the PEARLS study

 
Further information

 

Why are we doing this?

It is important to understand the best way to treat LS to reduce the long-term impact of the condition. If one treatment is better, patients in the future can be advised how best to manage their condition. Avoiding flares of LS and reducing scarring will improve the quality of life of patients and reduce need for treatments and support.
 

How will we involve patients and the public?

Two patient representatives are part of the study team. They are both women with LS. They have been involved in designing the study. We conducted an online survey involving 393 people with LS to inform the design of our study. Our patient representatives will continue to advise on the study as it progresses. We have also formed an advisory panel of women with LS and parents of girls with LS. This panel was consulted during the development process and will continue to contribute during the course of the study.
 

How will the results of the trial be shared?

The results of this study will be used to write clinical guidelines that doctors and patients will use to make decisions about their treatment. Everyone who takes part in the study will be sent the study results. We will also share them with patients via patient groups and social media, such as the UK LS support group on Facebook. The results will be written up in academic journals and shared at conferences.
 

How to get involved

If you live in the East Midlands or North West, and are willing to travel to the sites in Nottingham or Liverpool, have been diagnosed with lichen sclerosus and think that you might be eligible, please complete a short form. Your details will be picked up by a member of the team who will contact you to discuss your involvement. Alternatively, get in touch with the trial central team by email: PEARLS@nottingham.ac.uk or telephone: 0115 8231609/SKYPE 01157485961.

Expression of interest form

 

Privacy notice

This section explains how health researchers use information from participants. PEARLS study is run centrally by the Nottingham Clinical Trials Unit, which is part of the University of Nottingham.  The study is funded by National Institute for Health and Care Research (NIHR) Heath Technology Assessment (HTA) Ref: NIHR135121 and sponsored by the University of Nottingham.  The study is supported by hospitals and community hubs across the UK.  To answer the study research question, we aim to recruit 400 participants and collect data from them. Once we receive information about you, it will be processed to help study analysis and answer the research question. The sections below explain what processing of personal data is and how your data is protected in this study.

 

What is data processing?

“Data processing” is any operation performed on the data such as collection, use, management or disclosure.
 

What is personal data?

Personal “data” is information that relates to an identified or identifiable individual.  It does not include information relating to dead people, groups or communities of people, organisations or businesses. Nonetheless, the PEARLS study team will ensure they keep information confidential, safe and secure after the death of any individual taking part in the study.
 

Legal basis of data processing?

Any information we hold about the study participants is processed for the purposes of ‘the performance of a task carried out in the public interest’ (the Article 6(1)(e)) of the Data Protection Act 2018, and ‘scientific research’ (the Article 9(2)(j)) of the Data Protection Act 2018.

The EU General Data Protection 2016/679 (GDPR) came into regulation from 25 May 2018, which was thereafter supplemented by the DPA 2018.  The DPA 1998 covers how personal data may be lawfully processed (collected, used and shared).  This is referred as a “data protection law”.  The data protection law regulates how we process participants’ “personal data”.  Find out more how University of Nottingham processes your data: https://www.nottingham.ac.uk/utilities/privacy/privacy.aspx.

 

What personal data will be processed in this study?

The information we collect on the study participant may include and is not limited to:

  • Name, date of birth, NHS number
  • GP/hospital name and contact details
  • Medical information relevant to the study

During the study we will process further details on participants.  This may include:

  • Details about participation in the study
  • Outcomes of any procedures, tests; questionnaires undertaken as part of the study

Please note that personal details will be deleted when they are no longer needed.

 

How we manage personal information?

The Data Protection Act 2018 (DPA 2018) regulates the management of personal information.  This is how we look after personal information on study participants.  When we ask for participants’ personal information we:

  • make sure that the participant knows why it’s needed
  • ask only for minimum and sufficient information that is required and do not collect too much or irrelevant information
  • protect it and make sure no unauthorised person has access to it
  • let participants know if we share it with other organisations, which is necessary to improve public services
  • do not keep it for longer than it is necessary
  • inform participants that they can withdraw from the study any time
  • give contact details of a person/department/body to where enquires or complaints can be directed

Participants receive an ethically approved Participant Information Sheet (PIS) upon invitation to take part in the trial.  The PIS will detail information about the study, how participant information will be collected and handled and where it would be collected from.  The PIS will also explain what their involvement in the study would be.  In addition, the document will explain if other organisations will be involved in the study and what their roles are.

Potential participants will be given plenty of opportunity to ask the study related questions to a member of the research team.  In return we ask participants to:

  • give us accurate information
  • tell us as soon as possible if there are any changes to their personal circumstances such as contact details to enable us to keep the information reliable and up to date
 

What is the purpose of processing data?

We collect participants’ personal and healthcare data in order to answer the study questions.  Collecting personal information is necessary for traceability and collection of further data. The data will be collected directly from the study participants, medical records and may also be collected from NHS agencies.  The data will be directly relevant to answer the study specific question.  More information about the study can be found on the trial website.
 

Where do we collect data from?

The data will be normally collected either directly from participants or from medical records from the hospitals and GP practices.

To safeguard participants’ rights, we collect the minimum personally-identifiable information possible.

Some of the data we process is classed as ‘special category’ or sensitive personal data. This data may include information concerning health, racial or ethnic origin. 

 

What will we do with data obtained?

The study statisticians will analyse the data according to the statistical analysis plan.  The aggregate data (data from ALL participants without identifiers) will be published and disseminated among professionals.  Primarily, the study participants will be informed about the results of the study.
 

With whom will we share the data?

The PEARLS study involves many organisations such as hospitals recruiting participants, GP practices, the sponsor (University of Nottingham), Research Ethics Committee (REC), Medicines and Healthcare products Regulatory Agency (MHRA), the study oversight committees and study management group.  For the purposes of assessment and analysis of the study data or safety issues it may become necessary to share participants identifiable and healthcare information with these organisations during the study. 

The study team at the sites (hospitals) or authorised personnel from the sponsor and other regulatory bodies may look at the participants medical records.  This is necessary to ensure that the study is being conducted and managed to the highest possible standards.

Participant anonymised information may be occasionally shared with researchers of other ethically approved studies.  They may be based at the University of Nottingham, or any other universities, NHS organisations or companies involved in healthcare research in the UK or outside of the UK.  The access to information will be strictly controlled and anonymised before being shared.  Participants will not be identified in any way in any report, presentation or publication arising from this data sharing agreement.  The study team will ensure that appropriate safeguards are in place to protect the confidentiality and security of the participants’ data.

On some occasions, the study may be inspected by a third-party organisation to make sure that it is conducted in accordance with relevant requirements and legislation.  In such circumstances data sharing becomes necessary to meet legal and regulatory requirements and is only for the purposes of the audit.

 

How long will we keep the data?

The information collected on the study participants will be kept within the Nottingham Clinical Trials Unit (NCTU) and the hospital for a minimum of 7 years after the completion of the study.
 

Participants' rights in relation to their data & "Right to be forgotten"

The details on participants’ rights can be found on the https://www.nottingham.ac.uk/utilities/privacy/privacy.aspx.

Under the article 17 of GDPR the study participants have right to request “right to be forgotten” (aka “the erasure”) of their personal data without undue delay.  The trial subjects can request this verbally or in writing.  We have the obligation to erase the personal data without undue delay and will respond to this request typically within one month.

 

What happens if participants change their mind?

During the course of the study participants may change their mind about their data being included in the PEARLS study analysis.  The inclusion of their data is entirely up to the participant and choosing to do so will not disadvantage them in any way.  However, because the study is being conducted as a ‘task in the public interest’ and ‘scientific research’ according to the data protection law, a participant’s right to change or remove information may be limited.  This is because we need to process information in such ways that the research we carry out is at the highest standard, reliable, accurate and verifiable.  This means that we will keep the data that has already been obtained before a participant’s withdrawal from the study.
 

PEARLS data protection

When we ask you for information we will keep to the law, including the Data Protection Act 2018. Through appropriate management and strict controls, we will follow the 8 principles of data protection described in the act. Also see the Information Commissioners general guidance on the implementation of data protection.

We will also ensure that:

  • there is someone with specific responsibility for data protection in the organisation (the nominated person is called the Data Protection Coordinator)
  • everyone managing and handling personal information understands that they are contractually responsible for following good data protection practice, is appropriately trained to do so and is appropriately supervised
  • we deal with enquiries about how we handle personal information promptly and courteously
  • we describe how we handle personal information clearly, regularly review and audit how we manage personal information, and regularly assess and evaluate methods of handling personal information
 

 

 

 

 

 

Information for Healthcare Professionals

If you would like to read more about the PEARLS Trial, click below

PEARLS PROTOCOL Final v3.0 08-Aug-2024 (part 1) - signed

REC reference: 24/SW/0016

IRAS project ID: 1008267

ISCRTN: ISRCTN72275160

Clinical Trials Unit: Nottingham Clinical Trials Unit

Sponsor: University of Nottingham

Funder: National Institute for Health and Care Research (NIHR)

Recruitment Target: 400

Recruitment end date: 01 September 2025

 

Meet our team

Meet our Trial Team

Rosalind Simpson profile picture

Dr Rosalind Simpson is the Chief Investigator of PEARLS study. She is a consultant dermatologist at Nottingham University Hospitals and Associate Professor at the Centre of Evidence Based Dermatology, with an expertise in women’s health and vulval dermatology. She is research lead for the BSSVD, associate section editor at the British Journal of Dermatology and co-editor for the next edition of Rook’s Textbook of Dermatology. 

 

Kim Thomas women in SoM 1

Professor Kim Thomas is a Co-Chief Investigator on PEARLS study. She is a clinical trialist with an interest in skin disease and measurement of health outcomes in clinical trials. Kim is a co-Director of the Centre of Evidence Based Dermatology and an advisor to the National Institute for Clinical Excellence (NICE).  

janedaniels

Professor Jane Daniels is a Professor of Clinical Trials and Deputy Director of the Nottingham Clinical Trials Unit.  Her expertise includes Evaluation of diagnostic and screening tests, randomised trials of medical and surgical treatments, systematic reviews and meta-analysis. 

Sara Hillman

Dr Sarah Hillman has more than 20 years experience in obstetric practice. Her Research interests relate to GP training and workforce, genetics in primary and community care, Women's Health in primary and community care.  

 

VS Profile

Dr Vanitha Sivalingam is a consultant in Gynaecological Oncology at the Liverpool Women's Hospital, and Honorary NIHR Academic Clinical Lecturer in Gynaecological Oncology, Division of Cancer Sciences, University of Manchester. 

Sophie Rees

Dr Sophie Rees is a senior research fellow at Bristol University, with expertise in applied health research. Sophie uses qualitative and mixed methods in her research to understand the experience of health and illness, and of participating in and delivering clinical, psychological and behavioural interventions.

 TSachRS

Professor Tracey Sach is a Professor in Health Economics at the School of Primary Care, Population Sciences and Medical Education at the University of Southampton. Her research interests include economic evaluation methodology and application, particularly alongside randomised controlled trials.

 

 Simi

Dr Simi Sudhakaran is a Specialty Doctor in Dermatology at Hull University Teaching Hospitals NHS Trust and GP Partner at Modality Hull Division, working in a dual role covering both primary and secondary care. She is also the Clinical Director for Modality LLP Outpatients Clinics. 

 Image of Clare Boumhauer Patient representative

Clare Baumhauer, PPI is an active patient representative (PPI) and advocate for adults & children with lichen sclerosus & vulval cancer. She is a patient representative for the UK Dermatology Clinical Trials Network (UKDCTN) & on its Executive Committee. Clare also sits on the PAVE group (Patient Advisors for Vulval Research). 

20240226_H_Tess McPherson_resized

Dr Tess McPherson is a Consultant Dermatologist and Senior Clinical Lecturer (Oxford University Hospitals). She leads the paediatric dermatology service in Oxford. Her particular areas of specialism are Paediatric Dermatology, Adolescent Dermatology, General Dermatology, Atopic Eczema, Psoriasis, Acne, Psycho-Dermatology and Medical Student Education. 

 
reubenogollah

Reuben Ogollah is an Associate Professor of Medical Statistics and Clinical Trials at Nottingham Clinical Trials Unit. Reuben's main research interest is in the design, conduct, analysis and reporting of randomised controlled trials. 

toyinbello

Toyin Bello is a Medical Statistician at Nottingham Clinical Trials Uni. She has been working on different trials including studies evaluating medical devices and investigational medicinal products. Toyin's main research interest is in the design, conduct, analysis and reporting of RCTs and cRCTs.

Nicholas Russell

Nick Russell

 

 

hughjarrett

Hugh Jarrett is a Senior Trial Manager at Nottingham Clinical Trials Unit. He has extensive experience in clinical trials and has worked at a number of academic clinical trials with verious designs on UK-based, international and global studies. 

 tinagriffin profile photo

 Tina Griffin is a Trial Manager at Nottingham Clinical Trials Unit. She has worked on CTIMP, non-CTIMP trials and epidemiological studies across several academic units where she was committed to the development and maintenance of successful partnerships across different stakeholders.

 Helen

Helen Scott is a Trial Coordinator at Nottingham Clinical Trials Unit. Before joining the Unit she worked in the Centre for Evidence Based Dermatology in Nottingham on the RAPID Eczema Trials, a collaboration between citizen science and research academics. 

 

 

 

 

 

 

Larissa_John-200x200

Larissa John is a Trial Administrator at Nottingham Clinical Trials Unit. She completed her PhD at the MRC Centre for Medical Mycology at University of Exeter, where she researched antifungal combination therapies to improve the treatment of fungal infections.  

 

 

 
 

Contact us

If you have any queries, please contact the PEARLS trial team.

Email: PEARLS@nottingham.ac.uk

Tel: 0115 8231609 / SKYPE 01157485961

Address: Nottingham Clinical Trials Unit, Applied Health Research Building, University Park, The University of Nottingham, Nottingham, NG7 2RD

Important links:

http://www.ukdctn.org/news/pearls-study-funded-by-nihr.aspx 

 Follow us on: 

     @PEARLS_Trial

  @PEARLS_Nottingham

  @PEARLS_Trial_Nottingham