Clinical trial NCT05606523: Microbiota and Pancreatic Cancer Cachexia
Official title: Can Fecal Microbiota Transplantation of Cachectic Patients with Pancreas Cancer Impair Body Weight Gain in Germ-free Mice? the EXTRA Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Pancreatic Cancer
Microbiota
Cachexia
Lead sponsor: University Hospital, Geneva
Sponsor class: OTHER
First posted: 2022-11-04
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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.

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Body weight changes in mice after fecal material transplantation.
timeFrame: Between days 0 and 30
Secondary outcomes:
measure: Differences in fecal microbiota
timeFrame: at diagnosis
measure: Body weight
timeFrame: at diagnosis
measure: Waist-to-hip ratio
timeFrame: at diagnosis
measure: Fat mass
timeFrame: at diagnosis
measure: Fat-free mass
timeFrame: at diagnosis
measure: Muscle mass
timeFrame: at diagnosis
measure: Nutritional intake
timeFrame: at diagnosis
measure: Resting energy expenditure (REE)
timeFrame: at diagnosis
measure: Appetite
timeFrame: at diagnosis
measure: Appetite
timeFrame: at diagnosis
measure: Appetite
timeFrame: at diagnosis
measure: Appetite
timeFrame: at diagnosis
measure: Appetite
timeFrame: at diagnosis
measure: Appetite
timeFrame: at diagnosis
measure: Homeostatic model assessment (HOMA)-score
timeFrame: at diagnosis
measure: Glycemia
timeFrame: at diagnosis
measure: Insulinemia
timeFrame: at diagnosis
measure: Physical function
timeFrame: at diagnosis
measure: Physical activity
timeFrame: at diagnosis
measure: Quality of life
timeFrame: at diagnosis
measure: Mortality
timeFrame: at diagnosis
measure: Oral microbiota
timeFrame: at diagnosis
measure: Epithelial permeability
timeFrame: at diagnosis
measure: Epithelial permeability
timeFrame: at diagnosis
measure: Epithelial permeability
timeFrame: at diagnosis
measure: GALT function and systemic inflammation
timeFrame: at diagnosis
measure: GALT function and systemic inflammation
timeFrame: at diagnosis
measure: GALT function and systemic inflammation
timeFrame: at diagnosis
Other outcomes:
Locations:
city: Geneva
country: Switzerland
facility: Geneva University Hospitals
Study officials:
affiliation: Geneva University Hospitals (HUG)
name: Laurence Genton Graf, Prof
role: PRINCIPAL_INVESTIGATOR
References: