Neutrophil-mediated Inflammatory DermatosesNEUTROSKINNCT05732987
Genetic Architecture of Neutrophil-Mediated Inflammatory Skin Diseases
An observational study of Neutrophil-mediated Inflammatory Dermatoses and Inflammatory Dermatoses, run by University Hospital, Basel, Switzerland at 1 site in Switzerland.
Trial summary
This study is to identify rare, disease-causing mutations of several rare neutrophil dermatoses. To identify associations between NMID and variants in the genome next generation sequencing, mainly whole exome sequencing, will be used. Read more about this study
- Who is it for?
- Ages 18 to 100 yearsHealthy volunteers can take part
- Conditions the study is for
- Neutrophil-mediated Inflammatory Dermatoses, Inflammatory Dermatoses
- What is being tested?
- Analysis of samples
- How many people
- 3,370 participants
- Where
- 1 siteSwitzerland
- Study dates
- 3 Feb 2023to Sep 2029
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: The study participants will largely be recruited by a.) prospectively collected biopsies of patients from biobanks or b.) analyzing, contacting, and including/excluding the existing patient population of our clinic (FFPE tissues). Healthy skin is obtained from patients undergoing plastic surgery at the USB. These patients will be informed and their informed consent obtained before surgery.
Who may be able to join
- written consent of the participating person
- diagnosis of a disease in the NMID form group or proband of the control group
Who cannot join
- Missing informed consent if samples collected after 2014
- no diagnosis of NMID
- Missing informed consent
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Switzerland1 site, 1 recruiting
- Recruiting
University Hospital Basel, Clinic of Dermatology
Basel, 4031
Alexander Navarini, Prof. Dr. med., +41 61 265 40 84, alexander.navarini@usb.ch
Emmanuel Contassot, Dr., +41 61 328 55 45, emmanuel.contassot@usb.ch
About this study
Official title: Case-Control Study of the Genetic Architecture of Neutrophil-Mediated Inflammatory Skin Diseases
This study is to identify rare, disease-causing mutations of several rare neutrophil dermatoses. To identify associations between NMID and variants in the genome next generation sequencing, mainly whole exome sequencing, will be used. In a second approach the expression level of already known inflammatory proteins in skin samples will be investigated.
Read the detailed description
The origin of rare severe inflammatory skin diseases in dermatology is insufficiently known. They have in common the presence and activation of phagocytes, affect the quality of life through pain and inflammation and disfiguration, and can even be fatal. This study is intended to build on the findings that several of these neutrophil-mediated inflammatory dermatoses (NMID) have a genetic background and to identify rare, disease-causing mutations of several rare neutrophil dermatoses. This non-clinical case-control study is a research project with biological material and health-related data. To identify associations between NMID and variants in the genome next generation sequencing, mainly whole exome sequencing, will be used. In a second approach the expression level of already known inflammatory proteins in skin samples will be investigated. The data are obtained and verified using standardized methods as e.g. Nanostring, RNA sequencing and qRT-polymerase chain reaction (PCR), proteomics assays and immunohistochemistry as well as flow cytometry and imaging mass cytometry, ELISA, and Western Blot.
- Being tested
- Analysis of samples
- Keywords
- inflammasome, inflammation-driving pathway, gene variants, next generation sequencing
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Analysis of samplesOther
DNA extraction from blood or saliva samples for the identification of gene variants by next generation sequencing;
Analysis of samplesOther
RNA extraction from blood and skin samples for Nanostring analyses, quantitative RT-PCR or RNA sequencing.
Analysis of samplesOther
Biobanked skin samples will be analyzed by immunostaining and imaging techniques to identify cell types in lesions and compare them to healthy skin.
Analysis of samplesOther
Cells isolated from biobanked blood and skin samples will be cultured in vitro and proteins will be analyzed by ELISA (secreted proteins) and western blot (cell proteins).
| Study group | Role | What they receive |
|---|---|---|
| Biobank- samples from NMID patients | 600 samples from NMID patients from the Biobank Dermatology Unispital Basel (USB) (Biobank USB) and from the biobank of the Dermatology Department of the University Hospital Zürich (USZ) (Biobank USZ) will be included. Receives: Other: Analysis of samples | |
| Formalin-fixed and paraffin-embedded (FFPE) samples | About 50 of formalin-fixed and paraffin-embedded (FFPE) samples from the Dermatology USB collected before 2014 for RNA and protein expression analyses will be reused. The patients in questions are informed about the study and the coded use of their samples. Receives: Other: Analysis of samples | |
| Biobank- samples from controls | 2'700 anonymized control genomes as well as 150 anonymized control samples for the proteomics approach can be used as control samples from the biobank of the Dermatology Department of the University Hospital Zürich (Biobank Dermatology USZ). Receives: Other: Analysis of samples | |
| Fresh skin samples from healthy donors | A maximum of 20 fresh skin samples from healthy donors are required per skin location. They will be requested from healthy volunteers after information about the study and receiving the informed consent. Receives: Other: Analysis of samples |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of protein-coding rare variants associated with forms of NMID
The primary endpoint consists in the determination of association between newly identified or previously reported rare gene variants and one or more forms of NMIDs. The discovery of such genetic variants will lead to the identification of defective molecular mechanisms involved in abnormal cutaneous immune reactions in these patients: - Statistically significant association between genetic data and NMID
- Detection of protein-coding rare variants associated with forms of NMID
- Identification of inflammasome activation in different stages of NMID
Measured: one time assessment at baseline
Secondary outcomes (5)
Imaging Mass Cytometry
The secondary endpoint will consist in the determination of consequences at the molecular and cellular levels of gene variants and subsequently encoded proteins in the cutaneous lesions from NMID patients by the measurement of protein interactions and networks, immune cells, cytokines and receptors in forms of NMID by statistically significant association of selected reaction monitoring results including: -Imaging Mass Cytometry
Measured: one time assessment at baseline
RNA expression
The secondary endpoint will consist in the determination of consequences at the molecular and cellular levels of gene variants and subsequently encoded proteins in the cutaneous lesions from NMID patients by the measurement of protein interactions and networks, immune cells, cytokines and receptors in forms of NMID by statistically significant association of selected reaction monitoring results including: - RNA expression
Measured: one time assessment at baseline
Immune cell count
The secondary endpoint will consist in the determination of consequences at the molecular and cellular levels of gene variants and subsequently encoded proteins in the cutaneous lesions from NMID patients by the measurement of protein interactions and networks, immune cells, cytokines and receptors in forms of NMID by statistically significant association of selected reaction monitoring results including: - Immune cell count
Measured: one time assessment at baseline
Rate of mean fluorescence intensity of immune cells
The secondary endpoint will consist in the determination of consequences at the molecular and cellular levels of gene variants and subsequently encoded proteins in the cutaneous lesions from NMID patients by the measurement of protein interactions and networks, immune cells, cytokines and receptors in forms of NMID by statistically significant association of selected reaction monitoring results including: - Mean fluorescence intensity of immune cells
Measured: one time assessment at baseline
Protein quantification (ELISA)
The secondary endpoint will consist in the determination of consequences at the molecular and cellular levels of gene variants and subsequently encoded proteins in the cutaneous lesions from NMID patients by the measurement of protein interactions and networks, immune cells, cytokines and receptors in forms of NMID by statistically significant association of selected reaction monitoring results including: - Protein quantification (ELISA)
Measured: one time assessment at baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2023
- Study start3 Feb 2023
- Primary completionSep 2029 (estimated)
- Study completionSep 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neutrophil-mediated Inflammatory DermatosesStudies of the same condition, open and under way.
- More trials run by University Hospital, Basel, SwitzerlandThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 3,370 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Basel, Switzerland
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Alexander Navarini, Prof. Dr. med., Principal investigator, University Hospital Basel, Clinic of Dermatology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05732987
- Sponsor's protocol ID
- 2020-02645; sp19Navarini3
- Acronym
- NEUTROSKIN
- Status last verified
- Aug 2023
- First submitted
- 30 Jan 2023
- Last updated
- 22 Aug 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Case-Control Study of the Genetic Architecture of Neutrophil-Mediated Inflammatory Skin Diseases
- ClinicalTrials.gov ID
- NCT05732987
- Acronym / sponsor ID
- NEUTROSKIN / 2020-02645; sp19Navarini3
- Keywords
- inflammasome, inflammation-driving pathway, gene variants, next generation sequencing
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 3,370 participants (estimated)
- Lead sponsor
- University Hospital, Basel, SwitzerlandUniversity, hospital or other
- Study start
- 3 Feb 2023 (actual)
- Primary completion
- Sep 2029 (estimated)
- Study completion
- Sep 2029 (estimated)
- First posted
- 17 Feb 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is to identify rare, disease-causing mutations of several rare neutrophil dermatoses. To identify associations between NMID and variants in the genome next generation sequencing, mainly whole exome sequencing, will be used. In a second approach the expression level of already known inflammatory proteins in skin samples will be investigated.
Detailed description
The origin of rare severe inflammatory skin diseases in dermatology is insufficiently known. They have in common the presence and activation of phagocytes, affect the quality of life through pain and inflammation and disfiguration, and can even be fatal. This study is intended to build on the findings that several of these neutrophil-mediated inflammatory dermatoses (NMID) have a genetic background and to identify rare, disease-causing mutations of several rare neutrophil dermatoses. This non-clinical case-control study is a research project with biological material and health-related data. To identify associations between NMID and variants in the genome next generation sequencing, mainly whole exome sequencing, will be used. In a second approach the expression level of already known inflammatory proteins in skin samples will be investigated. The data are obtained and verified using standardized methods as e.g. Nanostring, RNA sequencing and qRT-polymerase chain reaction (PCR), proteomics assays and immunohistochemistry as well as flow cytometry and imaging mass cytometry, ELISA, and Western Blot.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Biobank- samples from NMID patients | – | Other: Analysis of samples600 samples from NMID patients from the Biobank Dermatology Unispital Basel (USB) (Biobank USB) and from the biobank of the Dermatology Department of the University Hospital Zürich (USZ) (Biobank USZ) will be included. |
| Formalin-fixed and paraffin-embedded (FFPE) samples | – | Other: Analysis of samplesAbout 50 of formalin-fixed and paraffin-embedded (FFPE) samples from the Dermatology USB collected before 2014 for RNA and protein expression analyses will be reused. The patients in questions are informed about the study and the coded use of their samples. |
| Biobank- samples from controls | – | Other: Analysis of samples2'700 anonymized control genomes as well as 150 anonymized control samples for the proteomics approach can be used as control samples from the biobank of the Dermatology Department of the University Hospital Zürich (Biobank Dermatology USZ). |
| Fresh skin samples from healthy donors | – | Other: Analysis of samplesA maximum of 20 fresh skin samples from healthy donors are required per skin location. They will be requested from healthy volunteers after information about the study and receiving the informed consent. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- The study participants will largely be recruited by a.) prospectively collected biopsies of patients from biobanks or b.) analyzing, contacting, and including/excluding the existing patient population of our clinic (FFPE tissues). Healthy skin is obtained from patients undergoing plastic surgery at the USB. These patients will be informed and their informed consent obtained before surgery.
Key inclusion criteria (2 listed)
- written consent of the participating person
- diagnosis of a disease in the NMID form group or proband of the control group
Key exclusion criteria (3 listed)
- Missing informed consent if samples collected after 2014
- no diagnosis of NMID
- Missing informed consent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Analysis of samplesDNA extraction from blood or saliva samples for the identification of gene variants by next generation sequencing; | Other | Biobank- samples from NMID patients, Biobank- samples from controls, Formalin-fixed and paraffin-embedded (FFPE) samples, Fresh skin samples from healthy donors |
| Analysis of samplesRNA extraction from blood and skin samples for Nanostring analyses, quantitative RT-PCR or RNA sequencing. | Other | Biobank- samples from NMID patients, Biobank- samples from controls, Formalin-fixed and paraffin-embedded (FFPE) samples, Fresh skin samples from healthy donors |
| Analysis of samplesBiobanked skin samples will be analyzed by immunostaining and imaging techniques to identify cell types in lesions and compare them to healthy skin. | Other | Biobank- samples from NMID patients, Biobank- samples from controls, Formalin-fixed and paraffin-embedded (FFPE) samples, Fresh skin samples from healthy donors |
| Analysis of samplesCells isolated from biobanked blood and skin samples will be cultured in vitro and proteins will be analyzed by ELISA (secreted proteins) and western blot (cell proteins). | Other | Biobank- samples from NMID patients, Biobank- samples from controls, Formalin-fixed and paraffin-embedded (FFPE) samples, Fresh skin samples from healthy donors |
Primary outcome
Number of protein-coding rare variants associated with forms of NMID
Time frame: one time assessment at baseline
The primary endpoint consists in the determination of association between newly identified or previously reported rare gene variants and one or more forms of NMIDs. The discovery of such genetic variants will lead to the identification of defective molecular mechanisms involved in abnormal cutaneous immune reactions in these patients: - Statistically significant association between genetic data and NMID * Detection of protein-coding rare variants associated with forms of NMID * Identification of inflammasome activation in different stages of NMID
5 secondary outcomes
Imaging Mass Cytometry
Time frame: one time assessment at baseline
RNA expression
Time frame: one time assessment at baseline
Immune cell count
Time frame: one time assessment at baseline
Rate of mean fluorescence intensity of immune cells
Time frame: one time assessment at baseline
Protein quantification (ELISA)
Time frame: one time assessment at baseline
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Alexander Navarini, Prof. Dr. med. principal investigator
University Hospital Basel, Clinic of Dermatology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Neutrophil-mediated Inflammatory Dermatoses and Inflammatory Dermatoses, run by University Hospital, Basel, Switzerland at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 22 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Alexander Navarini, Prof. Dr. med. (+41 61 265 40 84, alexander.navarini@usb.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of protein-coding rare variants associated with forms of NMID (time frame: one time assessment at baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Aug 2023.