The international ‘100 DU’ study
| ISRCTN | ISRCTN17000942 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN17000942 |
| Integrated Research Application System (IRAS) | 359781 |
| Central Portfolio Management System (CPMS) | 69727 |
| Sponsor | University of Manchester |
| Funders | Scleroderma Clinical Trials Consortium (SCTC), Scleroderma Research Foundation (SRF) |
- Submission date
- 23/07/2025
- Registration date
- 09/02/2026
- Last edited
- 10/03/2026
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Musculoskeletal Diseases
Plain English summary of protocol
Background and study aims
Digital ulcers (DU) are common in systemic sclerosis (SSc), affecting over half of patients during their disease course, with a point prevalence of approximately 10%. They are a major cause of pain, impaired function and reduced health-related quality of life. To date, clinical trials of SSc-DU have traditionally focused on clinician assessment of DU occurrence and healing, with comparatively little attention having focused on how patients with SSc-DU ‘feel’ and ‘function’, despite the importance placed on these clinically meaningful endpoints by regulators when considering marketing authorisation. The patient experience of SSc-DU has largely been captured using legacy patient-reported outcome (PRO) instruments such as the HAQ-DI (health assessment questionnaire disability index) and validated generic pain scales, which do not fully capture the multi-faceted lived experience of SSc-DU. There is an unmet need to develop a specific PRO instrument for use in clinical practice, observational studies and clinical trials to capture the impact of SSc-DU on how patients feel and function. The Scleroderma Clinical Trials Consortium (SCTC) Vascular Working Group have a strong track record for developing novel PRO instruments, having recently completed a five-year body of work to develop and validate the Assessment of Scleroderma-associated Raynaud’s Phenomenon (ASRAP) questionnaire for assessing SSc-RP. Prior SCTC Vascular Working Group seed-funding has enabled us to complete a comprehensive literature review and multicentre qualitative research study to explore the patient experience of SSc-DU. From this work, a conceptual map has been devised comprising five separate domains that encapsulate the lived patient experience of SSc-DU. The principal objective of this study is to elaborate and validate a novel PRO+ instrument for assessing the severity and impact of SSc-DU. SSc is a rare orphan disease (affecting around 200 people per million). A study of 100 patients will therefore represent a medium-sized study of this condition. The site, burden and aetiopathogenesis of SSc-DU differ between patients. Little is known about the contribution of DU burden (number and site of DU) and relevant aetiopathogenic driver (purely ischaemic versus mixed mechanical/inflammatory aetiology) on the lived patient experience of SSc-DU. The present proposal allows us to comprehensively examine the evolving patient experience of active DU using items from the preliminary SScDU questionnaire. A secondary objective will therefore be to understand the aetiopathogenic drivers of different types of DU (e.g. size, location) and their relationship to the lived patient experience of SSc-DU, and to benchmark DU healing (including impact of complications and treatment) in the modern era.
Who can participate?
Consecutive SSc patients will be enrolled to capture a representative sample of SSc patients for disease stage, organ complications and severity of vascular manifestations.
What does the study involve?
Participants will be consented and complete all self-administered questionnaires using the RedCap electronic data capture software. Clinicians will complete the case report form(s).
What are the possible benefits and risks of participating?
Recruited patients will be on an existing clinical pathway; it is anticipated that there are no additional benefits or risks with participation.
Where is the study run from?
The University of Manchester (UK)
When is the study starting and how long is it expected to run for?
July 2025 to December 2026
Who is funding the study?
The study is jointly funded by the Scleroderma Clinical Trials Consortium (SCTC) and the Scleroderma Research Foundation (SRF)
Who is the main contact?
Dr M Hughes, Clinical Senior Lecturer & Honorary Consultant Rheumatologist, Michael.hughes-6@manchester.ac.uk
Contact information
Public, Scientific, Principal investigator
The University of Manchester, Faculty of Biology Medicine & Health, School of Biological Sciences, Division of Musculoskeletal and Dermatological Sciences, Oxford Road
Manchester
M13 9PL
United Kingdom
| Phone | +44 (0)1613066000 |
|---|---|
| Michael.hughes-6@manchester.ac.uk |
Study information
| Primary study design | Observational |
|---|---|
| Study design | International multicentre longitudinal study |
| Secondary study design | Longitudinal study |
| Scientific title | Optimising the assessment and novel mechanistic insights into digital ulcers in systemic sclerosis: the international ‘100 DU’ study |
| Study objectives | The principal objective of this study is to elaborate and validate a novel patient-reported outcome (PRO) instrument for assessing the severity and impact of SSc-DU. |
| Ethics approval(s) |
1. Not yet submitted 2. Not yet submitted |
| Health condition(s) or problem(s) studied | Systemic sclerosis (SSc) with active digital ulceration (DU) |
| Intervention | This study is an international multicentre longitudinal study of 100 systemic sclerosis (SSc) patients with active digital ulceration (DU) from a diverse geographic, cultural and ethnic sample of patients enrolled from 15 English-speaking Scleroderma Clinical Trials Consortium (SCTC) sites in the UK, US, Australasia, and Canada. Observations to be made include questionnaires, clinician assessment, clinical photography and thermal imaging. To achieve our study aims, we have designed an international multicentre longitudinal study of 100 SSc patients with active DU from a diverse geographic, cultural and ethnic sample of patients enrolled from 15 English-speaking SCTC sites in the UK and US. The ‘100DU’ study will facilitate the comprehensive capture of patient-reported, clinician-assessed and imaging (photography and nailfold capillaroscopy) data from 100 SSc patients with active DU (including ischaemic, extensor and calcinosis-related ulceration) over 20 weeks. Applicable regulatory frameworks shall be adhered to at each participating unit, with local PIs retaining responsibility for local IRB approval and adherence to good practice. Data sharing MTAs shall be established between sites. The pragmatic study design shall include clinician assessments at 4-8 weeks and 18-22 weeks (attempting to mirror clinical practice) and benefit from self-administered PRO questionnaire completion at home. Patients will complete the study when/if their DU have been considered to have healed by their practising clinician. Participants will be consented and complete all self-administered questionnaires using the REDCap electronic data capture software. Clinicians will complete the case report form(s). The SSiDU questionnaire is a preliminary item bank comprising 29 items developed with the support of patient insight partners. Each item is grounded in the 5 major themes that encapsulate the patient experience of SSc-DU identified in our earlier literature review and qualitative research. The themes include physical symptoms and signs, psychological impacts, functional impact, aggravating factors and mitigating factors. At the initial study visit, participants in our planned multicentre study will support a prioritisation study to rank and score domains of activity and impact of SSc-DU important to patients with SSc. Patients will be presented with a list of the 5 major themes and an explanation regarding what is required of them. Participants shall be asked to sensibly rank the domains rather than individual issues. Specifically, they will rank each issue 1 to 9 (1-3 not necessary; 4-6 interesting but not essential; 7-9 essential) and then load questions by their relative mean scores. Domain loading would follow from the item loading. This shall inform the weighting and scoring of the final SSiDU instrument, with mean weightings derived for each domain from which a total SSiDU score can be derived. Participants will then complete the preliminary SSiDU item bank and a separate ‘pack’ of seven self-administered validated questionnaires (plus some additional details on smoking, ethnicity, work etc) and directly input their data into REDCap. A clinician CRF shall collect relevant information regarding patient demographics, clinical phenotype, clinician VAS scales and the DUCAS instrument. A limited physical examination of the hands, forearms and face to assess the number and distribution of digital ulcers, telangiectases and calcinosis. Clinicians shall document the site and size of active DU on CRF hand templates. They shall also document the site of calcinosis cutis and undertake a count of telangiectases within the hands and face (as proxy markers of cutaneous vascular severity). Additional face-to-face study visits will take place at weeks 6 (+/- 14 days) and 20 (+/- 14 days) to mirror typical routine care for active DU. These visits will either correspond to clinic reviews or additional research visits shall be arranged to accommodate. Participants will be given packs and free post envelopes at each study visit for between-study visit assessments at weeks 1 (+7 days) and week 12 (+/- 14 days). Patients will complete the study early when/if their DU have been considered to have healed by their practicing clinician at week 6 assessment. Prospective anchor questions (“My digital ulcer disease symptoms over the past week have been: very mild, mild, moderate, moderately severe, severe, very severe or unbearable.”) and retrospective anchor questions (“Consider all the ways that Digital Ulcer symptoms affect you, compared to the period running up to the 1st assessment, ‘how would you rate your overall Digital Ulcer symptoms since the last visit?’ (“much worse, somewhat worse, about the same, somewhat better, or much better”), will be used to establish Patient Acceptable Symptom States and Minimum Clinically Important Differences for the SSiDU questionnaire. Ancillary microvascular imaging study: Nailfold Capillaroscopy Nailfold capillaroscopy of four digits (two 1 mm images on either side of the midline of the middle and ring fingers bilaterally) shall be undertaken. Image analysis shall be undertaken centrally (Manchester, UK) and include qualitative: Cutolo grading of ‘early’, ‘active’ and ‘late’, and quantitative (including by planned utilisation of highly novel centralised automated analysis, Manchester, UK): mean number of capillaries per mm, mean inter-capillary distance, mean number of giant capillaries/microhaemorrhages, assessments. Ancillary microvascular imaging study: Thermal Image A thermal image of the dorsum of both hands shall be obtained. |
| Intervention type | Mixed |
| Primary outcome measure(s) |
The severity and impact of systemic sclerosis-related digital ulcers (SSc-DU) will be measured using the SSiDU questionnaire and self-administered validated questionnaires administered at baseline, week 1, week 6, week 12 and week 20. |
| Key secondary outcome measure(s) |
1. The severity and impact of systemic sclerosis-related digital ulcers (SSc-DU) will be measured using physical examination (assessment of site and status of DU (hands), telangiectases count (hands and face), calcinosis assessment (hands, elbow and knees), mRSS) at baseline, week 6 and week 20 |
| Completion date | 31/12/2026 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Lower age limit | 18 Years |
| Upper age limit | 100 Years |
| Sex | All |
| Target sample size at registration | 100 |
| Key inclusion criteria | 1. Participants will fulfil the 2013 European Union League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR) classification criteria for systemic sclerosis 2. The presence of an active DU at study entry. DU shall be defined according to the World Scleroderma Foundation (WSF) as “Loss of epidermal covering with a break in the basement membrane (which separates dermis from epidermis). It appears clinically as visible blood vessels, fibrin, granulation tissue and/or underlying deeper structures (e.g., muscle, ligament, fat) or as it would appear on debridement” 3. Male or female age ≥18 years 4. Patient is able and willing to follow the requirements of the study, including providing informed written consent 5. Good comprehension of written and spoken English |
| Key exclusion criteria | 1. Pregnant women 2. Patients with a change in their vasodilator medication within the previous 2 weeks before study entry |
| Date of first enrolment | 01/09/2025 |
| Date of final enrolment | 31/12/2026 |
Locations
Countries of recruitment
- United Kingdom
- England
- Australia
- Canada
- United States of America
Study participating centres
Southmead Road
Westbury-on-trym
Bristol
BS10 5NB
England
London
NW1 2PG
England
Leeds
LS2 9JT
England
Stott Lane
Salford
M6 8HD
England
Prescot Street
Liverpool
L7 8XP
England
Pensnett Road
Dudley
DY1 2HQ
England
United States of America
United States of America
United States of America
United States of America
United States of America
United States of America
Australia
Canada
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|
Editorial Notes
10/03/2026: Internal review.
05/08/2025: Study's existence confirmed by the Scleroderma Clinical Trials Consortium (SCTC).
