Microbiota and Pancreatic Cancer Cachexia

Genton Graf Laurence24 enrolled

Overview

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.

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 Type

OBSERVATIONAL

Enrollment

Conditions

Pancreatic Cancer Microbiota Cachexia

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (1)

Geneva University Hospitals

Geneva, Switzerland

RECRUITING

Outcomes

Primary Outcomes

Body weight changes in mice after fecal material transplantation.

Body weight (g)

Time frame: Between days 0 and 30

Secondary Outcomes

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

Time frame: at diagnosis

Body weight

in kilograms between cachectic patients non-cachectic patients and healthy volunteers

Time frame: at diagnosis

Waist-to-hip ratio

waist circumference (cm) and hip circumference (cm) between cachectic patients non-cachectic patients and healthy volunteers

Time frame: at diagnosis

Fat mass

by bioelectrical impedance analysis (BIA) between cachectic patients non-cachectic patients and healthy volunteers

Time frame: at diagnosis

Fat-free mass

by bioelectrical impedance analysis (BIA) between cachectic patients non-cachectic patients and healthy volunteers

Time frame: 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

Time frame: at diagnosis

Nutritional intake

by 3-day food diary between cachectic patients non-cachectic patients and healthy volunteers

Central Contacts

Laurence Genton Graf, Prof

CONTACT

+41 22 3729344 laurence.genton@hcuge.ch

Alexandra Hemmer, MSc

CONTACT

+41795530491 alexandra.hemmer@hcuge.ch

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Time frame: at diagnosis

Resting energy expenditure (REE)

by indirect calorimetry between cachectic patients non-cachectic patients and healthy volunteers

Time frame: at diagnosis

Appetite

by visual analogue scale ranging from 0 to 100 mm between cachectic patients non-cachectic patients and healthy volunteers

Time frame: at diagnosis

Appetite

by fasting level of plasma ghrelin between cachectic patients non-cachectic patients and healthy volunteers

Time frame: at diagnosis

Appetite

by fasting level of plasma leptin between cachectic patients non-cachectic patients and healthy volunteers

Time frame: at diagnosis

Appetite

by fasting level of plasma glucagon-like peptide-1 (GLP-1) between cachectic patients non-cachectic patients and healthy volunteers

Time frame: at diagnosis

Appetite

by fasting level of plasma neuropeptide Y between cachectic patients non-cachectic patients and healthy volunteers

Time frame: at diagnosis

Appetite

by fasting level of plasma cholecystokinin between cachectic patients non-cachectic patients and healthy volunteers

Time frame: 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

Time frame: at diagnosis

Glycemia

by fasting glycemia (mmol/l) between cachectic patients non-cachectic patients and healthy volunteers

Time frame: at diagnosis

Insulinemia

by fasting insulinemia (mU/ml) between cachectic patients non-cachectic patients and healthy volunteers

Time frame: at diagnosis

Physical function

by handgrip strength between cachectic patients non-cachectic patients and healthy volunteers

Time frame: at diagnosis

Physical activity

by the International Physical Activity Questionnaire (IPAQ) between cachectic patients non-cachectic patients and healthy volunteers

Time frame: 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

Time frame: at diagnosis

Mortality

by tumor progression between cachectic patients non-cachectic patients

Time frame: at diagnosis

Oral microbiota

by 16SrRNA gene amplicon sequencing and metagenomic sequencing between cachectic patients non-cachectic patients and healthy volunteers

Time frame: at diagnosis

Epithelial permeability

by fasting levels of plasma zonulin between cachectic patients non-cachectic patients and healthy volunteers

Time frame: at diagnosis

Epithelial permeability

by fasting levels of plasma lipopolysaccharide-binding protein between cachectic patients non-cachectic patients and healthy volunteers

Time frame: at diagnosis

Epithelial permeability

by fasting levels of plasma glucagon-like peptide-2 between cachectic patients non-cachectic patients and healthy volunteers

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: at diagnosis