EXTRA: Microbiota and Pancreatic Cancer Cachexia
Study Details
Study Description
Brief Summary
This monocentric study aims at evaluating the effects of fecal microbiota transplantation from newly diagnosed cachectic and non-cachectic pancreatic cancer patients, and healthy volunteers on several cachexia-related parameters of germ-free mice.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
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Detailed Description
Aim: Evaluating the effects of fecal microbiota transplantation (FMT) from 6 newly diagnosed cachectic and 6 non-cachectic pancreatic cancer patients, and 12 healthy age-and sex-matched volunteers on several cachexia-related parameters of 96 germ-free mice (4 per donor) over a 30-day period. The fecal material of all 12 pancreatic cancer patients will be collected at diagnosis before any cancer treatment onset.
Hypothesis: FMT of cachectic patients with pancreas cancer, naïve of any anti-cancer treatment and artificial nutrition, into germ-free mice impairs weight gain, in contrast to FMT of non-cachectic patients and healthy controls.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Cachectic patients with pancreatic cancer Measurements and sample collection at one timepoint. |
|
| Non-cachectic patients with pancreatic cancer Measurements and sample collection at one timepoint. |
|
| Healthy volunteers Measurements and sample collection at one timepoint. |
Outcome Measures
Primary Outcome Measures
- Body weight changes in mice after fecal material transplantation. [Between days 0 and 30]
Body weight (g)
Secondary Outcome Measures
- Differences in fecal microbiota [at diagnosis]
by 16S rRNA gene amplicon sequencing and functional profiles by metagenomic sequencing between cachectic patients non-cachectic patients and healthy volunteers
- Body weight [at diagnosis]
in kilograms between cachectic patients non-cachectic patients and healthy volunteers
- Waist-to-hip ratio [at diagnosis]
waist circumference (cm) and hip circumference (cm) between cachectic patients non-cachectic patients and healthy volunteers
- Fat mass [at diagnosis]
by bioelectrical impedance analysis (BIA) between cachectic patients non-cachectic patients and healthy volunteers
- Fat-free mass [at diagnosis]
by bioelectrical impedance analysis (BIA) between cachectic patients non-cachectic patients and healthy volunteers
- Muscle mass [at diagnosis]
surfaces of the paraspinal and abdominal wall muscles at the level of L3-L4 disk space by CT for pancreatic cancer patients
- Nutritional intake [at diagnosis]
by 3-day food diary between cachectic patients non-cachectic patients and healthy volunteers
- Resting energy expenditure (REE) [at diagnosis]
by indirect calorimetry between cachectic patients non-cachectic patients and healthy volunteers
- Appetite [at diagnosis]
by visual analogue scale ranging from 0 to 100 mm between cachectic patients non-cachectic patients and healthy volunteers
- Appetite [at diagnosis]
by fasting level of plasma ghrelin between cachectic patients non-cachectic patients and healthy volunteers
- Appetite [at diagnosis]
by fasting level of plasma leptin between cachectic patients non-cachectic patients and healthy volunteers
- Appetite [at diagnosis]
by fasting level of plasma glucagon-like peptide-1 (GLP-1) between cachectic patients non-cachectic patients and healthy volunteers
- Appetite [at diagnosis]
by fasting level of plasma neuropeptide Y between cachectic patients non-cachectic patients and healthy volunteers
- Appetite [at diagnosis]
by fasting level of plasma cholecystokinin between cachectic patients non-cachectic patients and healthy volunteers
- Homeostatic model assessment (HOMA)-score [at diagnosis]
by fasting glycemia (mmol/l) and fasting insulinemia (mU/ml)) between cachectic patients non-cachectic patients and healthy volunteers
- Glycemia [at diagnosis]
by fasting glycemia (mmol/l) between cachectic patients non-cachectic patients and healthy volunteers
- Insulinemia [at diagnosis]
by fasting insulinemia (mU/ml) between cachectic patients non-cachectic patients and healthy volunteers
- Physical function [at diagnosis]
by handgrip strength between cachectic patients non-cachectic patients and healthy volunteers
- Physical activity [at diagnosis]
by the International Physical Activity Questionnaire (IPAQ) between cachectic patients non-cachectic patients and healthy volunteers
- Quality of life [at diagnosis]
by the European Organisation for Research and Treatment of Cancer questionnaire (EORTC QLQ-C30) between cachectic patients non-cachectic patients and healthy volunteers
- Mortality [at diagnosis]
by tumor progression between cachectic patients non-cachectic patients
- Oral microbiota [at diagnosis]
by 16SrRNA gene amplicon sequencing and metagenomic sequencing between cachectic patients non-cachectic patients and healthy volunteers
- Epithelial permeability [at diagnosis]
by fasting levels of plasma zonulin between cachectic patients non-cachectic patients and healthy volunteers
- Epithelial permeability [at diagnosis]
by fasting levels of plasma lipopolysaccharide-binding protein between cachectic patients non-cachectic patients and healthy volunteers
- Epithelial permeability [at diagnosis]
by fasting levels of plasma glucagon-like peptide-2 between cachectic patients non-cachectic patients and healthy volunteers
- GALT function and systemic inflammation [at diagnosis]
by fasting plasma level of C-reactive protein (CRP) and cytokines between cachectic patients non-cachectic patients and healthy volunteers
- GALT function and systemic inflammation [at diagnosis]
by peripheral blood T regulatory cells (Tregs) levels and phenotype between cachectic patients non-cachectic patients and healthy volunteers
- GALT function and systemic inflammation [at diagnosis]
by myeloid derived suppressor cells (MDSC) levels and phenotype between cachectic patients non-cachectic patients and healthy volunteers
Eligibility Criteria
Criteria
Inclusion Criteria:
Patients with pancreatic cancer (n=12)
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≥18 years and
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Newly diagnosed of pancreatic adenocarcinoma (local or metastatic) and
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Tube feeding or parenteral nutrition ≤ 14 days
Cachectic pancreatic cancer patients (n=6)
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Cachexia according to the Fearon criteria 1: involuntary weight loss >5% over the last 6 months, or any level of weight loss >2% and a BMI <20 kg/m2 or sarcopenia. Sarcopenia will be diagnosed by BIA (fat-free mass index is <17 kg/m2 in men and <15 kg/m2 in women) 81, and not by CT, as it is faster and can be performed at the bedside of the patient. Non-cachectic pancreatic cancer patients (n=6)
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Normal nutritional state: weight stability (± 2% of habitual weight) over the last 6 months, no anorexia before the diagnosis (appetite rating on a visual analogue scale of 100mm), no known impaired glucose tolerance.
Healthy matched subjects (n=12)
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≥18 years and
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BMI between 18.5 and 30 kg/m2 and
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Absence of chronic or acute disease and
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Matching for gender and age (± 5 years) with an included pancreatic cancer patient
Exclusion Criteria:
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< 18 years or
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Inability to give consent or
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Insufficient knowledge of project language (French, German) or
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Pancreatic adenocarcinoma already treated by chemo- or radiotherapy, or major surgery as duodenopancreatectomy or biliary diversion
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Known rheumatologic or immunologic diseases
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Therapeutic antibiotics or immunosuppressive drugs (for instance glucocorticoids, cytostatics, antibodies) in the 30 days preceding the inclusion
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Geneva University Hospitals | Geneva | Switzerland | 1211 |
Sponsors and Collaborators
- Genton Graf Laurence
Investigators
- Principal Investigator: Laurence Genton Graf, Prof, Geneva University Hospitals (HUG)
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2022-00820