Microbiota and Pancreatic Cancer Cachexia

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Can Fecal Microbiota Transplantation of Cachectic Patients With Pancreas Cancer Impair Body Weight Gain in Germ-free Mice? The EXTRA Study

Conditions
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Pancreatic Cancer, Microbiota, Cachexia

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with pancreatic cancer (n=12) ≥18 years and Newly diagnosed of pancreatic adenocarcinoma (local or metastatic) and Tube feeding or parenteral nutrition ≤ 14 days Cachectic pancreatic cancer patients (n=6) 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) 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) ≥18 years and BMI between 18.5 and 30 kg/m2 and Absence of chronic or acute disease and Matching for gender and age (± 5 years) with an included pancreatic cancer patient Exclusion Criteria: < 18 years or Inability to give consent or Insufficient knowledge of project language (French, German) or Pancreatic adenocarcinoma already treated by chemo- or radiotherapy, or major surgery as duodenopancreatectomy or biliary diversion Known rheumatologic or immunologic diseases Therapeutic antibiotics or immunosuppressive drugs (for instance glucocorticoids, cytostatics, antibodies) in the 30 days preceding the inclusion

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cachectic patients with pancreatic cancer<br>Measurements and sample collection at one timepoint. | |
| Non-cachectic patients with pancreatic cancer<br>Measurements and sample collection at one timepoint. | |
| Healthy volunteers<br>Measurements and sample collection at one timepoint. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body weight changes in mice after fecal material transplantation. | Body weight (g) | Between days 0 and 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences in fecal microbiota | by 16S rRNA gene amplicon sequencing and functional profiles by metagenomic sequencing between cachectic patients non-cachectic patients and healthy volunteers | at diagnosis | 
| Body weight | in kilograms between cachectic patients non-cachectic patients and healthy volunteers | at diagnosis | 
| Waist-to-hip ratio | waist circumference (cm) and hip circumference (cm) between cachectic patients non-cachectic patients and healthy volunteers | at diagnosis | 
| Fat mass | by bioelectrical impedance analysis (BIA) between cachectic patients non-cachectic patients and healthy volunteers | at diagnosis | 
| Fat-free mass | by bioelectrical impedance analysis (BIA) between cachectic patients non-cachectic patients and healthy volunteers | at diagnosis | 
| Muscle mass | surfaces of the paraspinal and abdominal wall muscles at the level of L3-L4 disk space by CT for pancreatic cancer patients | at diagnosis | 
| Nutritional intake | by 3-day food diary between cachectic patients non-cachectic patients and healthy volunteers | at diagnosis | 
| Resting energy expenditure (REE) | by indirect calorimetry between cachectic patients non-cachectic patients and healthy volunteers | at diagnosis | 
| Appetite | by visual analogue scale ranging from 0 to 100 mm between cachectic patients non-cachectic patients and healthy volunteers | at diagnosis | 
| Appetite | by fasting level of plasma ghrelin between cachectic patients non-cachectic patients and healthy volunteers | at diagnosis | 
| Appetite | by fasting level of plasma leptin between cachectic patients non-cachectic patients and healthy volunteers | at diagnosis | 
| Appetite | by fasting level of plasma glucagon-like peptide-1 (GLP-1) between cachectic patients non-cachectic patients and healthy volunteers | at diagnosis | 
| Appetite | by fasting level of plasma neuropeptide Y between cachectic patients non-cachectic patients and healthy volunteers | at diagnosis | 
| Appetite | by fasting level of plasma cholecystokinin between cachectic patients non-cachectic patients and healthy volunteers | at diagnosis | 
| Homeostatic model assessment (HOMA)-score | by fasting glycemia (mmol/l) and fasting insulinemia (mU/ml)) between cachectic patients non-cachectic patients and healthy volunteers | at diagnosis | 
| Glycemia | by fasting glycemia (mmol/l) between cachectic patients non-cachectic patients and healthy volunteers | at diagnosis | 
| Insulinemia | by fasting insulinemia (mU/ml) between cachectic patients non-cachectic patients and healthy volunteers | at diagnosis | 
| Physical function | by handgrip strength between cachectic patients non-cachectic patients and healthy volunteers | at diagnosis | 
| Physical activity | by the International Physical Activity Questionnaire (IPAQ) between cachectic patients non-cachectic patients and healthy volunteers | at diagnosis | 
| Quality of life | by the European Organisation for Research and Treatment of Cancer questionnaire (EORTC QLQ-C30) between cachectic patients non-cachectic patients and healthy volunteers | at diagnosis | 
| Mortality | by tumor progression between cachectic patients non-cachectic patients | at diagnosis | 
| Oral microbiota | by 16SrRNA gene amplicon sequencing and metagenomic sequencing between cachectic patients non-cachectic patients and healthy volunteers | at diagnosis | 
| Epithelial permeability | by fasting levels of plasma zonulin between cachectic patients non-cachectic patients and healthy volunteers | at diagnosis | 
| Epithelial permeability | by fasting levels of plasma lipopolysaccharide-binding protein between cachectic patients non-cachectic patients and healthy volunteers | at diagnosis | 
| Epithelial permeability | by fasting levels of plasma glucagon-like peptide-2 between cachectic patients non-cachectic patients and healthy volunteers | at diagnosis | 
| GALT function and systemic inflammation | by fasting plasma level of C-reactive protein (CRP) and cytokines between cachectic patients non-cachectic patients and healthy volunteers | at diagnosis | 
| GALT function and systemic inflammation | by peripheral blood T regulatory cells (Tregs) levels and phenotype between cachectic patients non-cachectic patients and healthy volunteers | at diagnosis | 
| GALT function and systemic inflammation | by myeloid derived suppressor cells (MDSC) levels and phenotype between cachectic patients non-cachectic patients and healthy volunteers | at diagnosis |