Characterization and Clinical Impact of the Gut Microbiota in Lymphoma
- Conditions
- Diffuse Large B Cell Lymphoma
- Interventions
- Diagnostic Test: Stool samples
- Registration Number
- NCT06161896
- Lead Sponsor
- Lars Møller Pedersen
- Brief Summary
The study is a prospective observational single-center cohort study which compare the gut microbiome of newly diagnosed Diffuse Large B-cell Lymphoma patients with the gut microbiome of healthy controls. Furthermore the impact of lymphoma treatment, immune phenotypes, cytokine profiles, metabolomics, inflammation, driver mutations, comorbidity, body composition and lifestyle on the microbiome is also investigated
- Detailed Description
Microbiota refers to an ecological community of commensal, symbiotic and pathogenic microorganisms that colonize the various compartments within the human body including the gastrointestinal tract. The composition has been shown to play an important role in the pathophysiology of many diseases as well as influence host homeostatic processes such as regulation of metabolic processes, defense against pathogens, immune system development, regulation of the immune response and inflammation. However, the connection between the gut microbiota and lymphoma remain poorly understood.
The purpose of this study is to evaluate the composition and diversity of the gut microbiome in a large homogeneous group of patients with newly diagnosed and treatment-naive Diffuse Large B-cell Lymphoma (DLBCL). The investigators aim to identify the relationship between the intestinal microbiota, clinical and molecular subtypes of DLBCL and outcome of the disease. The association between nutrition, physical activity, body composition, toxicity to the antineoplastic therapy, infections, use of antibiotics, comorbidity and tumor genetics versus gut microbiota composition and diversity is also explored.
The project is carried out in collaboration between clinical departments, institutes and laboratories with expertise in microbiology, hematology, pathology, nutrition, molecular biology, immunology and bioinformatics.
Hypothesis of the study are:
1. Patients with DLBCL have distinct baseline microbiota signatures that differ from healthy subjects.
2. Significant changes in the microbiota composition and diversity can be identified during and after treatment (immunochemotherapy) of DLBCL.
3. Lymphoma response and outcome is affected by the composition and diversity of the DLBCL microbiota.
4. The intestinal microbiota changes towards a microbiota more like the microbiota of healthy controls in patients who remain in lymphoma remission one year after completion of therapy.
5. Distinct DLBCL microbiota profiles are associated with treatment-related toxicity.
6. The intestinal microbiota affects the risk of infections (clinically and/or microbiologically documented).
7. The intestinal microbiota is affected using antibiotics both as prophylaxis and treatment of infections.
8. The DLBCL microbiota depends on the dietary intake, smoking, physical activity and the body composition.
9. Distinct intestinal microbiota signatures can be associated with molecular subtypes of DLBCL (or vice versa)
10. The JAK2V617F, TET2, DNMT3A and ASXL1 mutations affect the intestinal microbiota signature and are associated with comorbidity and outcome in DLBCL
11. There is a vicious circle between intestinal dysbiosis and lymphoma with the crosstalk between the gut microbiota and the cancer being expressed as alterations in the profile of cytokines, chemokines and growth factors; an immune response reflected by immunophenotypic profiles of peripheral blood mononuclear cells; and characteristic metabolite signatures in the blood.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 200
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description DLBCL cohort Stool samples Interventions for the DLBCL cohort are: * Fecal samples * Blood samples * Bioelectrical impedance analyses * Filling in questionnaires All other procedures will be in accordance with local and national guidelines corresponding to clinical standard care. Healthy control cohort Stool samples The control group applied in the current study is based on the Danish General Suburban Population Study (GESUS). The control subjects are selected from the GESUS cohort and matched according to age and gender. Serial stool samples are planned in a subset of the control cohort with sampling time points corresponding to the DLBCL cohort. The sample material is handled and stored the same way as for the DLBCL cohort.
- Primary Outcome Measures
Name Time Method Intestinal microbiota baseline characterization 1.5 years Assessment using amplicon-based sequencing of ribosomal (r)RNA genes
- Secondary Outcome Measures
Name Time Method Chromosome abnormalities 1.5 years Molecular signatures in standard clinical practice (fluorescent in situ hybridization (FISH))
Intestinal microbiota characterization at mid-, post-treatment and at follow up 2.5 years Assessment using amplicon-based sequencing of ribosomal (r)RNA genes
Infections 1.5 years Clinical infections during treatment
Lymphoma response 1.5 years Lymphoma response after completion of first line treatment (Lugano criteria)
Mutations 1.5 years JAK2V617F, TET2, DNMT3A and ASXL1 mutation analyses (%VAF)
Alcohol intake 2.5 years Units (baseline lifestyle questionnaire)
Peripheral blood mononuclear cell (PBMC) profiles 1.5 years PBMC profiles according to flow cytometry
Assessment of energy and macronutrient intake 2.5 years 24h dietary recalls
Treatment-related toxicity 1.5 years Treatment-related toxicity (CTCAE criteria)
Statins 1.5 years Use of any type of statins during treatment registered in the Shared Medication Record (FMK)
Assessment of habitual diet 2.5 years Food frequency questionnaire (FFQ)
Body composition 2.5 years Body composition according to bioelectrical impedance analysis (BIA) using BioScan touch i8 - IVF version
Antibiotics 1.5 years Use of any type of prophylactic and therapeutic antibiotics during treatment (baseline lifestyle questionnaire)
Molecular signatures 1.5 years Molecular signatures in standard clinical practice according to Hans classification (cell of origin (COO))
Cytokine profiles 1.5 years Magnetic bead-based assays
Assessment of physical activity 2.5 years International physical activity questionnaire (IPAQ)
Smoking 2.5 years Packages (baseline lifestyle questionnaire)
Medication 1.5 years Use of any type of medication registered in the Shared Medication Record (FMK)
Metabolite signatures 1.5 years Metabolomic profiling by a combination of GC and LC coupled with MS
Trial Locations
- Locations (1)
Zealand University Hospital, Department of Hematology
🇩🇰Roskilde, Zealand, Denmark