DERMATOMICS: Identifying Regulators of Skin Homeostasis (DERMATOMICS)

Diseases of the skin associated with chronic immune driven conditions, including scleroderma, lupus, dermatomyositis, psoriasis, and atopic dermatitis, significantly impact skin integrity, function, and overall quality of life. These conditions can lead to severe disfigurement, discomfort, and systemic complications, necessitating long-term medical intervention. The prevalence of these skin disorders is rising globally, driven by genetic, environmental, and immunological factors. Unravelling the mechanisms leading to skin manifestations may shed further insights in the overall mechanisms of disease.

The DERMATOMICS study will focus on understanding systemic sclerosis (SSc) biology.

Systemic Sclerosis (SSc) is a highly heterogeneous rare autoimmune fibrotic condition affecting the skin and internal organs. SSc is classified as a Connective Tissue Disease (CTD), a family of conditions including Systemic Lupus Erythematosus, Sjogren Syndrome and Inflammatory Myositis, all characterised by an autoimmune process affecting the connective tissue of most organs, communed by the presence of anti-nuclear antibodies (ANA). In SSc, patients are affected by a combination of tissue and vascular fibrosis, on the background of a chronic inflammatory process, leading to the highest per patient morbidity and mortality across CTDs. The main driver of mortality to date is interstitial lung disease (ILD), which is the consequence of the fibrotic involvement of the lungs, leading to a progressive loss of functional lung volumes, and ultimately, derangement of lung circulation, hypoxia, increased risk of hospitalisation for lower respiratory infections and death.

Current treatments for CTDs include general immunosuppressive treatments, not necessarily targeted to the specific mechanisms underlying their presentation, focusing on reducing inflammation and managing symptoms rather than addressing the underlying causes. Many of these therapies have limited effectiveness or are burdened with significant side effects. Therefore, there is a critical need to develop a comprehensive understanding of the cellular and molecular mechanisms underlying these disorders to identify novel therapeutic targets.

Several factors contribute to the risk and severity of SSc, including genetic predisposition, environmental triggers, immune system dysregulation, and lifestyle factors such as diet and smoking. The interactions between these factors are complex and not fully understood. By recruiting participants with SSc, we aim to obtain skin punch biopsies for detailed molecular and genetic analysis. To increase the informative value of our study we plan to implement an extreme phenotype approach and include participants with opposite degrees of severity.

Our study aims to elucidate the relationships between the molecular biology of skin cells, skin structure, genetic factors ("DNA"), and environmental influences. The goal is to identify and validate novel therapeutic targets that can lead to more effective and personalised treatment options for SSc, and more broadly for CTDs and CTD-associated skin and lung disease.

Modern single-cell technologies will be employed to dissect the cellular diversity within the skin. These advanced techniques have revolutionised our understanding of many tissues, but skin tissues remain underexplored, especially in the context of chronic skin diseases. Protocols for skin punch biopsy and single-cell profiling are well-established, allowing us to systematically analyse how genetic variations influence skin structure and function.

Study Overview

• Status: Recruiting
• Conditions: Systemic Sclerosis (SSc)
• Intervention / Treatment: Procedure: Skin punch biopsy; Other: blood sampling; Behavioral: Questionnaire

• Study Type: Observational
• Enrollment (Estimated): 500

Contacts and Locations

Study Locations

• United Kingdom
  • Leeds, United Kingdom, LS7 4SA
    • Not yet recruiting
    • Chapel Allerton Hospital
    • Contact: Sumit Lahiri; Phone Number: 01133924879; Email: sumit.lahiri@nhs.net
  • London, United Kingdom, NW3 2Qg
    • Recruiting
    • Royal Free Hospital
    • Contact: Kimberley Morlese; Phone Number: 34274 0207 317 7544; Email: kimberley.morlese@nhs.net

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Participants with either early systemic sclerosis (SSc) or late systemic sclerosis (SSc)

Description

Inclusion Criteria:

SSc participant cohort:

1. Age of 18 years inclusive, or older at the time of signing the informed consent
2. Documented diagnosis of systemic scleroderma (SSc) (early or late diagnosis)

Healthy cohort:

1. Approximate age/sex matching (majority of healthy participants to be recruited after cohort 1 and 2)
2. Absence of Raynaud's Phenomenon
3. Absence of lung disease
4. Not on immunosuppressive treatment

Exclusion Criteria:

SSc participant cohort:

1. Participants unable to provide informed consent.
2. Participants with suspected/established underlying malignancy.
3. Participants with suspected/established skin cancer.
4. Participants with suspected/established bloodborne disease.
5. Current enrolment or past participation in a study involving an investigational drug within 3 months or 5 half-lives of the investigational drug treatment (whichever is longer) before the day of sample collection.
6. Participants treated with cellular therapies, e.g., HSCT, Car-T cells, T cell engagers.
7. Participants treated with B-cell depletion therapies within 6 months.
8. Concurrent diagnosis of any other connective tissue disease (CTD) in overlap.
9. Diagnosis of other non-SSc dermatological conditions.
10. Systemic sclerosis-like illness, including but not limited to localised scleroderma (morphoea), eosinophilic fasciitis, sclerodermoid graft-versus-host disease, fibro mucinous conditions (scleredema, scleromyxedema), scleroderma-like conditions that are associated with environmental chemical and drug exposure (e.g., toxic rapeseed oil, vinyl chloride, bleomycin, gadolinium-based contrast agents [nephrogenic systemic fibrosis], or due to metabolic disease).
11. History or presence of significant non-sclereoderma related cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematologic, neurological disorders, or treatments for those, capable of significantly interfering with the results and interpretation of data.
12. Smoking history (5 years smoke free acceptable)

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Early SSc cohort; Early diagnosis of systemic sclerosis (SSc)	Procedure: Skin punch biopsy; Skin punch biopsies are 5mm for this study. Participants with SSc will undergo 4 biopsies (2 in diseased area, 2 in non-diseased area if available). Healthy Volunteers will undergo 2 biopsies.; Other: blood sampling; 10mls blood will be taken for analysis and DNA sequencing; Behavioral: Questionnaire; All participants are required to complete a questionnaire with information on demographics, lifestyle, medical and medication history.
Late SSc cohort; Late diagnosis of systemic sclerosis (SSc)	Procedure: Skin punch biopsy; Skin punch biopsies are 5mm for this study. Participants with SSc will undergo 4 biopsies (2 in diseased area, 2 in non-diseased area if available). Healthy Volunteers will undergo 2 biopsies.; Other: blood sampling; 10mls blood will be taken for analysis and DNA sequencing; Behavioral: Questionnaire; All participants are required to complete a questionnaire with information on demographics, lifestyle, medical and medication history.
Healthy cohort (control); Absence of SSc and Raynaud's Phenomenon (controls for the SSc cohorts)	Procedure: Skin punch biopsy; Skin punch biopsies are 5mm for this study. Participants with SSc will undergo 4 biopsies (2 in diseased area, 2 in non-diseased area if available). Healthy Volunteers will undergo 2 biopsies.; Other: blood sampling; 10mls blood will be taken for analysis and DNA sequencing; Behavioral: Questionnaire; All participants are required to complete a questionnaire with information on demographics, lifestyle, medical and medication history.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acquisition of skin samples	Skin samples acquired from skin punch biopsies to be used for the study of RNA.	Within 48 hours of sampling

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acquisition of 10ml of blood	Blood to use used for genetic sequencing, and/or other downstream omics/assays	Within 48 hours of sampling
Completion of participant questionnaire	Participant metadata to be used to understand cohort and identify confounding factors	EDC entry within 1 week of skin & blood samples being taken.

Collaborators and Investigators

• Sponsor: Relation Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): December 10, 2024
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2030

Study Registration Dates

• First Submitted: March 18, 2025
• First Submitted That Met QC Criteria: March 18, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): July 28, 2025
• Last Update Submitted That Met QC Criteria: July 23, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Skin; systemic sclerosis; Scleroderma; SSc
• Additional Relevant MeSH Terms: Pathologic Processes; Connective Tissue Diseases; Skin Diseases; Sclerosis; Scleroderma, Systemic; Scleroderma, Diffuse
• Other Study ID Numbers: RRx-Profiling-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

A pharmaceutical partner is providing funding support to a research collaboration with Relation Therapeutics and will be involved in data review.

It is intended that the results of the study will be published when appropriate. There will be no reference in the study results / reports / publications to any information that would identify participants. The final dataset, which may include a small number of select fields from the EDC database, will not contain any identifiable personal data.

• IPD Sharing Time Frame: Data will not be released until the study is complete. Raw data files in the original format (e.g. fastq) and the accompanying anonymised phenotypic data will be uploaded to a public repository e.g. the NCBI database of Genotypes and Phenotypes (dbGaP) at https://www.ncbi.nlm.nih.gov/gap/.
• IPD Sharing Access Criteria: Any database selected to host genetic data must require legally-binding data access agreements with participating researchers.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No