AYLo - AutoimmunitY and Loss of y

NCT ID: NCT06696027

Last Updated: 2025-04-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

500 participants

Study Classification

OBSERVATIONAL

Study Start Date

2024-11-15

Study Completion Date

2026-07-31

Brief Summary

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The AYLo study (AutoimmunitY and Loss of y - Investigating the Role of Hematopoietic Mutations and Mosaic Mutation in the Y Chromosome in Autoimmune Rheumatologic Diseases) aims to systematically investigate hematopoietic mutations, such as hematopoietic (mosaic) loss of the Y chromosome (mLOY), focusing on their underlying causes, pathophysiological significance, patterns of manifestation, and impact on disease progression in autoimmune, rheumatologic disorders. This research seeks to bridge existing knowledge gaps by exploring how such mutations influence immune homeostasis, cellular function, and susceptibility to inflammation-driven pathologies.

Through the integration of advanced immunological profiling, the study aspires to uncover key mechanisms that drive the initiation, progression, and complications of autoimmune rheumatic diseases. These analyses will combine single nucleotide polymorphisms (SNP) arrays, multiplex assays, transcriptomics, and flow cytometry staining of peripheral blood mononuclear cells to delineate the interplay between hematopoietic mutations and immune dysregulation.

A further objective is the development of a multimodal framework for disease-specific characterization, enabling precise mapping of mutation-driven phenotypes across diverse autoimmune conditions. This framework will incorporate clinical, molecular, and imaging data.

Additionally, the AYLo study aims to explore the potential role of mLOY and other hematopoietic mutations as biomarkers for disease stratification, prognosis, and therapeutic response. The findings may open avenues for personalized treatment approaches, leveraging the molecular insights to inform targeted interventions and improve patient outcomes in autoimmune rheumatic disorders.

By integrating translational and basic science approaches, this study has the potential to redefine current paradigms in autoimmune disease research and therapy.

Detailed Description

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Conditions

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Giant Cell Arteritis (GCA) Polymyalgia Rheumatica (PMR) ANCA Associated Vasculitis (AAV) Idiopathic Inflammatory Myopathies IgG4-Related Diseases Rheumatoid Arthritis (RA) Psoriatic Arthritis (PsA) Connective Tissue Disease Sarcoidosis Interstitial Lung Disease Due to Systemic Disease (Disorder) Interstitial Lung Disease (ILD) Asthma Bronchiale COPD

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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Giant Cell Arteritis (GCA)

Patients with GCA (cross sectional, newly diagnosed with follow-up after twelve months).

Single nucleotide polymorphisms (SNP)

Intervention Type DIAGNOSTIC_TEST

Utilizing single nucleotide polymorphisms (SNP) genotyping mosaic loss of y (mLOY) of individual patient will be assessed.

3'mRNA sequencing

Intervention Type DIAGNOSTIC_TEST

3'mRNA sequencing analyzes gene expression profiles related to the immune response in different study cohorts, aiding in understanding the genetic underpinnings of inflammation and its association with mLOY.

Enzyme-linked immunosorbent assay (ELISA) and Legendplex Array

Intervention Type DIAGNOSTIC_TEST

Used to measure cytokine levels in the serum of investigated patients, aiding in profiling inflammatory markers that are indicative of disease activity, response to treatment and consequence of mLOY..

Flow Cytometry

Intervention Type DIAGNOSTIC_TEST

Employed to analyze immune cell phenotypes in investigated cohorts. This test helps identify various immune cell subsets and their activation states, which are critical for understanding disease mechanisms and its association with mLOY.

Laboratory assessment

Intervention Type DIAGNOSTIC_TEST

Serum Chemistry

Polymyalgia Rheumatica (PMR)

Patients with PMR (cross sectional, newly diagnosed with follow-up after twelve months).

Single nucleotide polymorphisms (SNP)

Intervention Type DIAGNOSTIC_TEST

Utilizing single nucleotide polymorphisms (SNP) genotyping mosaic loss of y (mLOY) of individual patient will be assessed.

3'mRNA sequencing

Intervention Type DIAGNOSTIC_TEST

3'mRNA sequencing analyzes gene expression profiles related to the immune response in different study cohorts, aiding in understanding the genetic underpinnings of inflammation and its association with mLOY.

Enzyme-linked immunosorbent assay (ELISA) and Legendplex Array

Intervention Type DIAGNOSTIC_TEST

Used to measure cytokine levels in the serum of investigated patients, aiding in profiling inflammatory markers that are indicative of disease activity, response to treatment and consequence of mLOY..

Flow Cytometry

Intervention Type DIAGNOSTIC_TEST

Employed to analyze immune cell phenotypes in investigated cohorts. This test helps identify various immune cell subsets and their activation states, which are critical for understanding disease mechanisms and its association with mLOY.

Laboratory assessment

Intervention Type DIAGNOSTIC_TEST

Serum Chemistry

ANCA Associated Vasculitis (AAV)

Patients with AAV (cross sectional, newly diagnosed with follow-up after twelve months).

Single nucleotide polymorphisms (SNP)

Intervention Type DIAGNOSTIC_TEST

Utilizing single nucleotide polymorphisms (SNP) genotyping mosaic loss of y (mLOY) of individual patient will be assessed.

3'mRNA sequencing

Intervention Type DIAGNOSTIC_TEST

3'mRNA sequencing analyzes gene expression profiles related to the immune response in different study cohorts, aiding in understanding the genetic underpinnings of inflammation and its association with mLOY.

Enzyme-linked immunosorbent assay (ELISA) and Legendplex Array

Intervention Type DIAGNOSTIC_TEST

Used to measure cytokine levels in the serum of investigated patients, aiding in profiling inflammatory markers that are indicative of disease activity, response to treatment and consequence of mLOY..

Flow Cytometry

Intervention Type DIAGNOSTIC_TEST

Employed to analyze immune cell phenotypes in investigated cohorts. This test helps identify various immune cell subsets and their activation states, which are critical for understanding disease mechanisms and its association with mLOY.

Laboratory assessment

Intervention Type DIAGNOSTIC_TEST

Serum Chemistry

Assessment of Pulmonary Involvement

Intervention Type DIAGNOSTIC_TEST

Results of routine clinical assessment of pulmonary involvement (such as lung ultrasound, computed tomography, chest x-ray, whole-body plethysmography) will be compared to mLOY, ELISA/ Legendplex/ flow cytometry/ transcriptome analysis results.

IgG4 Related Diseases

Patients with IgG4 Related Diseases (cross sectional, newly diagnosed with follow-up after twelve months).

Single nucleotide polymorphisms (SNP)

Intervention Type DIAGNOSTIC_TEST

Utilizing single nucleotide polymorphisms (SNP) genotyping mosaic loss of y (mLOY) of individual patient will be assessed.

3'mRNA sequencing

Intervention Type DIAGNOSTIC_TEST

3'mRNA sequencing analyzes gene expression profiles related to the immune response in different study cohorts, aiding in understanding the genetic underpinnings of inflammation and its association with mLOY.

Enzyme-linked immunosorbent assay (ELISA) and Legendplex Array

Intervention Type DIAGNOSTIC_TEST

Used to measure cytokine levels in the serum of investigated patients, aiding in profiling inflammatory markers that are indicative of disease activity, response to treatment and consequence of mLOY..

Flow Cytometry

Intervention Type DIAGNOSTIC_TEST

Employed to analyze immune cell phenotypes in investigated cohorts. This test helps identify various immune cell subsets and their activation states, which are critical for understanding disease mechanisms and its association with mLOY.

Laboratory assessment

Intervention Type DIAGNOSTIC_TEST

Serum Chemistry

Idiopathic Inflammatory Myopathies (IIM)

Patients with IIM (cross sectional, newly diagnosed with follow-up after twelve months).

Single nucleotide polymorphisms (SNP)

Intervention Type DIAGNOSTIC_TEST

Utilizing single nucleotide polymorphisms (SNP) genotyping mosaic loss of y (mLOY) of individual patient will be assessed.

3'mRNA sequencing

Intervention Type DIAGNOSTIC_TEST

3'mRNA sequencing analyzes gene expression profiles related to the immune response in different study cohorts, aiding in understanding the genetic underpinnings of inflammation and its association with mLOY.

Enzyme-linked immunosorbent assay (ELISA) and Legendplex Array

Intervention Type DIAGNOSTIC_TEST

Used to measure cytokine levels in the serum of investigated patients, aiding in profiling inflammatory markers that are indicative of disease activity, response to treatment and consequence of mLOY..

Flow Cytometry

Intervention Type DIAGNOSTIC_TEST

Employed to analyze immune cell phenotypes in investigated cohorts. This test helps identify various immune cell subsets and their activation states, which are critical for understanding disease mechanisms and its association with mLOY.

Laboratory assessment

Intervention Type DIAGNOSTIC_TEST

Serum Chemistry

Assessment of Pulmonary Involvement

Intervention Type DIAGNOSTIC_TEST

Results of routine clinical assessment of pulmonary involvement (such as lung ultrasound, computed tomography, chest x-ray, whole-body plethysmography) will be compared to mLOY, ELISA/ Legendplex/ flow cytometry/ transcriptome analysis results.

Rheumatoid Arthritis (RA)

Patients with RA (cross sectional, newly diagnosed with follow-up after twelve months).

Single nucleotide polymorphisms (SNP)

Intervention Type DIAGNOSTIC_TEST

Utilizing single nucleotide polymorphisms (SNP) genotyping mosaic loss of y (mLOY) of individual patient will be assessed.

3'mRNA sequencing

Intervention Type DIAGNOSTIC_TEST

3'mRNA sequencing analyzes gene expression profiles related to the immune response in different study cohorts, aiding in understanding the genetic underpinnings of inflammation and its association with mLOY.

Enzyme-linked immunosorbent assay (ELISA) and Legendplex Array

Intervention Type DIAGNOSTIC_TEST

Used to measure cytokine levels in the serum of investigated patients, aiding in profiling inflammatory markers that are indicative of disease activity, response to treatment and consequence of mLOY..

Flow Cytometry

Intervention Type DIAGNOSTIC_TEST

Employed to analyze immune cell phenotypes in investigated cohorts. This test helps identify various immune cell subsets and their activation states, which are critical for understanding disease mechanisms and its association with mLOY.

Laboratory assessment

Intervention Type DIAGNOSTIC_TEST

Serum Chemistry

Assessment of Pulmonary Involvement

Intervention Type DIAGNOSTIC_TEST

Results of routine clinical assessment of pulmonary involvement (such as lung ultrasound, computed tomography, chest x-ray, whole-body plethysmography) will be compared to mLOY, ELISA/ Legendplex/ flow cytometry/ transcriptome analysis results.

Psoriatic Arthritis (PsA)

Patients with PsA (cross sectional, newly diagnosed with follow-up after twelve months).

Single nucleotide polymorphisms (SNP)

Intervention Type DIAGNOSTIC_TEST

Utilizing single nucleotide polymorphisms (SNP) genotyping mosaic loss of y (mLOY) of individual patient will be assessed.

3'mRNA sequencing

Intervention Type DIAGNOSTIC_TEST

3'mRNA sequencing analyzes gene expression profiles related to the immune response in different study cohorts, aiding in understanding the genetic underpinnings of inflammation and its association with mLOY.

Enzyme-linked immunosorbent assay (ELISA) and Legendplex Array

Intervention Type DIAGNOSTIC_TEST

Used to measure cytokine levels in the serum of investigated patients, aiding in profiling inflammatory markers that are indicative of disease activity, response to treatment and consequence of mLOY..

Flow Cytometry

Intervention Type DIAGNOSTIC_TEST

Employed to analyze immune cell phenotypes in investigated cohorts. This test helps identify various immune cell subsets and their activation states, which are critical for understanding disease mechanisms and its association with mLOY.

Laboratory assessment

Intervention Type DIAGNOSTIC_TEST

Serum Chemistry

Assessment of Pulmonary Involvement

Intervention Type DIAGNOSTIC_TEST

Results of routine clinical assessment of pulmonary involvement (such as lung ultrasound, computed tomography, chest x-ray, whole-body plethysmography) will be compared to mLOY, ELISA/ Legendplex/ flow cytometry/ transcriptome analysis results.

Connective Tissue Diseases (CTD)

Patients with CTD (cross sectional, newly diagnosed with follow-up after twelve months).

Single nucleotide polymorphisms (SNP)

Intervention Type DIAGNOSTIC_TEST

Utilizing single nucleotide polymorphisms (SNP) genotyping mosaic loss of y (mLOY) of individual patient will be assessed.

3'mRNA sequencing

Intervention Type DIAGNOSTIC_TEST

3'mRNA sequencing analyzes gene expression profiles related to the immune response in different study cohorts, aiding in understanding the genetic underpinnings of inflammation and its association with mLOY.

Enzyme-linked immunosorbent assay (ELISA) and Legendplex Array

Intervention Type DIAGNOSTIC_TEST

Used to measure cytokine levels in the serum of investigated patients, aiding in profiling inflammatory markers that are indicative of disease activity, response to treatment and consequence of mLOY..

Flow Cytometry

Intervention Type DIAGNOSTIC_TEST

Employed to analyze immune cell phenotypes in investigated cohorts. This test helps identify various immune cell subsets and their activation states, which are critical for understanding disease mechanisms and its association with mLOY.

Laboratory assessment

Intervention Type DIAGNOSTIC_TEST

Serum Chemistry

Assessment of Pulmonary Involvement

Intervention Type DIAGNOSTIC_TEST

Results of routine clinical assessment of pulmonary involvement (such as lung ultrasound, computed tomography, chest x-ray, whole-body plethysmography) will be compared to mLOY, ELISA/ Legendplex/ flow cytometry/ transcriptome analysis results.

Sarcoidosis

Patients with sarcoidosis (cross sectional, newly diagnosed with follow-up after twelve months).

Single nucleotide polymorphisms (SNP)

Intervention Type DIAGNOSTIC_TEST

Utilizing single nucleotide polymorphisms (SNP) genotyping mosaic loss of y (mLOY) of individual patient will be assessed.

3'mRNA sequencing

Intervention Type DIAGNOSTIC_TEST

3'mRNA sequencing analyzes gene expression profiles related to the immune response in different study cohorts, aiding in understanding the genetic underpinnings of inflammation and its association with mLOY.

Enzyme-linked immunosorbent assay (ELISA) and Legendplex Array

Intervention Type DIAGNOSTIC_TEST

Used to measure cytokine levels in the serum of investigated patients, aiding in profiling inflammatory markers that are indicative of disease activity, response to treatment and consequence of mLOY..

Flow Cytometry

Intervention Type DIAGNOSTIC_TEST

Employed to analyze immune cell phenotypes in investigated cohorts. This test helps identify various immune cell subsets and their activation states, which are critical for understanding disease mechanisms and its association with mLOY.

Laboratory assessment

Intervention Type DIAGNOSTIC_TEST

Serum Chemistry

Assessment of Pulmonary Involvement

Intervention Type DIAGNOSTIC_TEST

Results of routine clinical assessment of pulmonary involvement (such as lung ultrasound, computed tomography, chest x-ray, whole-body plethysmography) will be compared to mLOY, ELISA/ Legendplex/ flow cytometry/ transcriptome analysis results.

Interstitial Lung Diseases (ILD)

Patients with ILD (cross sectional, newly diagnosed with follow-up after twelve months).

Single nucleotide polymorphisms (SNP)

Intervention Type DIAGNOSTIC_TEST

Utilizing single nucleotide polymorphisms (SNP) genotyping mosaic loss of y (mLOY) of individual patient will be assessed.

3'mRNA sequencing

Intervention Type DIAGNOSTIC_TEST

3'mRNA sequencing analyzes gene expression profiles related to the immune response in different study cohorts, aiding in understanding the genetic underpinnings of inflammation and its association with mLOY.

Enzyme-linked immunosorbent assay (ELISA) and Legendplex Array

Intervention Type DIAGNOSTIC_TEST

Used to measure cytokine levels in the serum of investigated patients, aiding in profiling inflammatory markers that are indicative of disease activity, response to treatment and consequence of mLOY..

Flow Cytometry

Intervention Type DIAGNOSTIC_TEST

Employed to analyze immune cell phenotypes in investigated cohorts. This test helps identify various immune cell subsets and their activation states, which are critical for understanding disease mechanisms and its association with mLOY.

Laboratory assessment

Intervention Type DIAGNOSTIC_TEST

Serum Chemistry

Assessment of Pulmonary Involvement

Intervention Type DIAGNOSTIC_TEST

Results of routine clinical assessment of pulmonary involvement (such as lung ultrasound, computed tomography, chest x-ray, whole-body plethysmography) will be compared to mLOY, ELISA/ Legendplex/ flow cytometry/ transcriptome analysis results.

Chronic Obstructive Pulmonary Disease (COPD)

Patients with COPD (cross sectional, newly diagnosed with follow-up after twelve months).

Single nucleotide polymorphisms (SNP)

Intervention Type DIAGNOSTIC_TEST

Utilizing single nucleotide polymorphisms (SNP) genotyping mosaic loss of y (mLOY) of individual patient will be assessed.

3'mRNA sequencing

Intervention Type DIAGNOSTIC_TEST

3'mRNA sequencing analyzes gene expression profiles related to the immune response in different study cohorts, aiding in understanding the genetic underpinnings of inflammation and its association with mLOY.

Enzyme-linked immunosorbent assay (ELISA) and Legendplex Array

Intervention Type DIAGNOSTIC_TEST

Used to measure cytokine levels in the serum of investigated patients, aiding in profiling inflammatory markers that are indicative of disease activity, response to treatment and consequence of mLOY..

Flow Cytometry

Intervention Type DIAGNOSTIC_TEST

Employed to analyze immune cell phenotypes in investigated cohorts. This test helps identify various immune cell subsets and their activation states, which are critical for understanding disease mechanisms and its association with mLOY.

Laboratory assessment

Intervention Type DIAGNOSTIC_TEST

Serum Chemistry

Assessment of Pulmonary Involvement

Intervention Type DIAGNOSTIC_TEST

Results of routine clinical assessment of pulmonary involvement (such as lung ultrasound, computed tomography, chest x-ray, whole-body plethysmography) will be compared to mLOY, ELISA/ Legendplex/ flow cytometry/ transcriptome analysis results.

Asthma Bronchiale

Patients with asthma bronchiale (cross sectional, newly diagnosed with follow-up after twelve months).

Single nucleotide polymorphisms (SNP)

Intervention Type DIAGNOSTIC_TEST

Utilizing single nucleotide polymorphisms (SNP) genotyping mosaic loss of y (mLOY) of individual patient will be assessed.

3'mRNA sequencing

Intervention Type DIAGNOSTIC_TEST

3'mRNA sequencing analyzes gene expression profiles related to the immune response in different study cohorts, aiding in understanding the genetic underpinnings of inflammation and its association with mLOY.

Enzyme-linked immunosorbent assay (ELISA) and Legendplex Array

Intervention Type DIAGNOSTIC_TEST

Used to measure cytokine levels in the serum of investigated patients, aiding in profiling inflammatory markers that are indicative of disease activity, response to treatment and consequence of mLOY..

Flow Cytometry

Intervention Type DIAGNOSTIC_TEST

Employed to analyze immune cell phenotypes in investigated cohorts. This test helps identify various immune cell subsets and their activation states, which are critical for understanding disease mechanisms and its association with mLOY.

Laboratory assessment

Intervention Type DIAGNOSTIC_TEST

Serum Chemistry

Assessment of Pulmonary Involvement

Intervention Type DIAGNOSTIC_TEST

Results of routine clinical assessment of pulmonary involvement (such as lung ultrasound, computed tomography, chest x-ray, whole-body plethysmography) will be compared to mLOY, ELISA/ Legendplex/ flow cytometry/ transcriptome analysis results.

Healthy Control Group

Age-/ gender matched healthy controls

Single nucleotide polymorphisms (SNP)

Intervention Type DIAGNOSTIC_TEST

Utilizing single nucleotide polymorphisms (SNP) genotyping mosaic loss of y (mLOY) of individual patient will be assessed.

3'mRNA sequencing

Intervention Type DIAGNOSTIC_TEST

3'mRNA sequencing analyzes gene expression profiles related to the immune response in different study cohorts, aiding in understanding the genetic underpinnings of inflammation and its association with mLOY.

Enzyme-linked immunosorbent assay (ELISA) and Legendplex Array

Intervention Type DIAGNOSTIC_TEST

Used to measure cytokine levels in the serum of investigated patients, aiding in profiling inflammatory markers that are indicative of disease activity, response to treatment and consequence of mLOY..

Flow Cytometry

Intervention Type DIAGNOSTIC_TEST

Employed to analyze immune cell phenotypes in investigated cohorts. This test helps identify various immune cell subsets and their activation states, which are critical for understanding disease mechanisms and its association with mLOY.

Laboratory assessment

Intervention Type DIAGNOSTIC_TEST

Serum Chemistry

Assessment of Pulmonary Involvement

Intervention Type DIAGNOSTIC_TEST

Results of routine clinical assessment of pulmonary involvement (such as lung ultrasound, computed tomography, chest x-ray, whole-body plethysmography) will be compared to mLOY, ELISA/ Legendplex/ flow cytometry/ transcriptome analysis results.

Interventions

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Single nucleotide polymorphisms (SNP)

Utilizing single nucleotide polymorphisms (SNP) genotyping mosaic loss of y (mLOY) of individual patient will be assessed.

Intervention Type DIAGNOSTIC_TEST

3'mRNA sequencing

3'mRNA sequencing analyzes gene expression profiles related to the immune response in different study cohorts, aiding in understanding the genetic underpinnings of inflammation and its association with mLOY.

Intervention Type DIAGNOSTIC_TEST

Enzyme-linked immunosorbent assay (ELISA) and Legendplex Array

Used to measure cytokine levels in the serum of investigated patients, aiding in profiling inflammatory markers that are indicative of disease activity, response to treatment and consequence of mLOY..

Intervention Type DIAGNOSTIC_TEST

Flow Cytometry

Employed to analyze immune cell phenotypes in investigated cohorts. This test helps identify various immune cell subsets and their activation states, which are critical for understanding disease mechanisms and its association with mLOY.

Intervention Type DIAGNOSTIC_TEST

Laboratory assessment

Serum Chemistry

Intervention Type DIAGNOSTIC_TEST

Assessment of Pulmonary Involvement

Results of routine clinical assessment of pulmonary involvement (such as lung ultrasound, computed tomography, chest x-ray, whole-body plethysmography) will be compared to mLOY, ELISA/ Legendplex/ flow cytometry/ transcriptome analysis results.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

* Male
* \> 50 years
* Diagnosis of arthritis (RA, PsA), collagen diseases (SLE, systemic sclerosis, Sjögren's syndrome, mixed connective tissue diseases), vasculitis (eGPA, GPA, MPA, IgG4-related disease, GCA, PMR), sarcoidosis, COPD, ILD or asthma bronchiale confirmed by the treating physician.


* Male
* \> 50 years

Exclusion Criteria

* Female
* \< 50 years


* Female
* \< 50 years
* autoimmune, rheumatological diease
* pulmonary precondition
Minimum Eligible Age

50 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Yes

Sponsors

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University of Bonn

OTHER

Sponsor Role lead

Responsible Party

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Valentin Schäfer

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Department of Rheumatology

Bonn, North Rhine-Westphalia, Germany

Site Status RECRUITING

Countries

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Germany

Central Contacts

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Simon Michael Petzinna, MD

Role: CONTACT

0049 151 382 337 07

Valentin Sebastian Schäfer, MD

Role: CONTACT

0049 228 287 17000

Facility Contacts

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Valentin Sebastian Schäfer, MD

Role: primary

0049 228 287 17000

Other Identifiers

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2024-471-BO

Identifier Type: -

Identifier Source: org_study_id

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