Microbiota and Pancreatic Cancer Cachexia

Pancreatic Cancer Clinical Trial

— EXTRA  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05606523
• Other study ID #: 2022-00820
• Status: Recruiting
• Start date: August 1, 2022
• Est. completion date: April 30, 2025

Study information

• Verified date: November 2023
• Source: University Hospital, Geneva
• Contact: Laurence Genton Graf, Prof
• Phone: +41 22 3729344
• Email: laurence.genton[@]hcuge.ch
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: April 30, 2025
• Est. primary completion date: April 30, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cachexia
• Microbiota
• Pancreatic Cancer
• Pancreatic Neoplasms

Locations

Country	Name	City	State
Switzerland	Geneva University Hospitals	Geneva

Sponsors (1)

Lead Sponsor	Collaborator
Genton Graf Laurence

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Body weight changes in mice after fecal material transplantation.	Body weight (g)	Between days 0 and 30
Secondary	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
Secondary	Body weight	in kilograms between cachectic patients non-cachectic patients and healthy volunteers	at diagnosis
Secondary	Waist-to-hip ratio	waist circumference (cm) and hip circumference (cm) between cachectic patients non-cachectic patients and healthy volunteers	at diagnosis
Secondary	Fat mass	by bioelectrical impedance analysis (BIA) between cachectic patients non-cachectic patients and healthy volunteers	at diagnosis
Secondary	Fat-free mass	by bioelectrical impedance analysis (BIA) between cachectic patients non-cachectic patients and healthy volunteers	at diagnosis
Secondary	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
Secondary	Nutritional intake	by 3-day food diary between cachectic patients non-cachectic patients and healthy volunteers	at diagnosis
Secondary	Resting energy expenditure (REE)	by indirect calorimetry between cachectic patients non-cachectic patients and healthy volunteers	at diagnosis
Secondary	Appetite	by visual analogue scale ranging from 0 to 100 mm between cachectic patients non-cachectic patients and healthy volunteers	at diagnosis
Secondary	Appetite	by fasting level of plasma ghrelin between cachectic patients non-cachectic patients and healthy volunteers	at diagnosis
Secondary	Appetite	by fasting level of plasma leptin between cachectic patients non-cachectic patients and healthy volunteers	at diagnosis
Secondary	Appetite	by fasting level of plasma glucagon-like peptide-1 (GLP-1) between cachectic patients non-cachectic patients and healthy volunteers	at diagnosis
Secondary	Appetite	by fasting level of plasma neuropeptide Y between cachectic patients non-cachectic patients and healthy volunteers	at diagnosis
Secondary	Appetite	by fasting level of plasma cholecystokinin between cachectic patients non-cachectic patients and healthy volunteers	at diagnosis
Secondary	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
Secondary	Glycemia	by fasting glycemia (mmol/l) between cachectic patients non-cachectic patients and healthy volunteers	at diagnosis
Secondary	Insulinemia	by fasting insulinemia (mU/ml) between cachectic patients non-cachectic patients and healthy volunteers	at diagnosis
Secondary	Physical function	by handgrip strength between cachectic patients non-cachectic patients and healthy volunteers	at diagnosis
Secondary	Physical activity	by the International Physical Activity Questionnaire (IPAQ) between cachectic patients non-cachectic patients and healthy volunteers	at diagnosis
Secondary	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
Secondary	Mortality	by tumor progression between cachectic patients non-cachectic patients	at diagnosis
Secondary	Oral microbiota	by 16SrRNA gene amplicon sequencing and metagenomic sequencing between cachectic patients non-cachectic patients and healthy volunteers	at diagnosis
Secondary	Epithelial permeability	by fasting levels of plasma zonulin between cachectic patients non-cachectic patients and healthy volunteers	at diagnosis
Secondary	Epithelial permeability	by fasting levels of plasma lipopolysaccharide-binding protein between cachectic patients non-cachectic patients and healthy volunteers	at diagnosis
Secondary	Epithelial permeability	by fasting levels of plasma glucagon-like peptide-2 between cachectic patients non-cachectic patients and healthy volunteers	at diagnosis
Secondary	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
Secondary	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
Secondary	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