Microbiota and Pancreatic Cancer Cachexia (EXTRA)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Pancreatic Cancer; Cachexia; Microbiota

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 Type: Observational
• Enrollment (Estimated): 24

Contacts and Locations

• Study Contact: Name: Laurence Genton Graf, Prof; Phone Number: +41 22 3729344; Email: laurence.genton@hcuge.ch
• Study Contact Backup: Name: Alexandra Hemmer, MSc; Phone Number: +41795530491; Email: alexandra.hemmer@hcuge.ch

Study Locations

• Switzerland
  • Geneva, Switzerland, 1211
    • Recruiting
    • Geneva University Hospitals
    • Contact: Laurence Genton Graf, Prof
    • Principal Investigator: Laurence Genton Graf, Prof

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

We will consider the fecal samples of 12 patients at diagnosis of pancreatic cancer including 6 patients with cachexia and 6 patients without cachexia, and therefore naïve of any anti-cancer treatment and artificial nutritional support. We will also include 12 healthy volunteers matched for gender and age (± 5 years) with the pancreatic cancer patients.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Genton Graf Laurence
• Investigators: Principal Investigator: Laurence Genton Graf, Prof, Geneva University Hospitals (HUG)

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2022
• Primary Completion (Estimated): April 30, 2024
• Study Completion (Estimated): April 30, 2025

Study Registration Dates

• First Submitted: August 25, 2022
• First Submitted That Met QC Criteria: October 31, 2022
• First Posted (Actual): November 4, 2022

Study Record Updates

• Last Update Posted (Actual): November 28, 2023
• Last Update Submitted That Met QC Criteria: November 27, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Metabolic Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Nutrition Disorders; Body Weight; Body Weight Changes; Pancreatic Diseases; Weight Loss; Thinness; Pancreatic Neoplasms; Wasting Syndrome; Cachexia
• Other Study ID Numbers: 2022-00820

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No