Primary objective:Effect of fecal transplantation (from healthy obese donors) on faecel microbiota composition in relation to satiety (questionnaires, biomarkers) and metabolism (REE ) in patients with metastasized or locally advanced oesophageal or…
ID
Source
Brief title
Condition
- Appetite and general nutritional disorders
- Muscle disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Faecal gut microbiota composition (morning stool samples)
Satiety, measured by: 1. Visual Analog Scale (VAS) 2. Plasma markers for
satiety (tryptophan, ghrelin, leptin, neuropeptide Y and orexin levels) 3.
Energy expenditure, measured by indirect calorimetry.
Secondary outcome
- Sarcopenia (muscle mass measured by CT-based analysis and grip strength)
- Body composition (measured by Bio Impedance Analysis)
- Faecal energy excretion (caloric bomb method) and short chain fatty acid and
bile acid concentration (2x24h collected faeces) and urine excretion of 5-HIAA
(24 h collected urine).
- Systemic inflammation and gut barrier function (CRP, plasma interleukins/LPS
binding protein levels and fecal calprotectin) in relation to energy
metabolism as measured by resting energy expenditure (REE).
- Chemotherapy toxicity, graded with the Common Terminology Criteria for
Adverse Events (CTCAE)11
- Treatment response measured by CT-scan at baseline and after the first 3
cycles of chemotherapy (week 12).
- Overall survival (defined as the number of days of survival after PA
diagnosis).
Background summary
Sarcopenia, the loss of skeletal muscle mass and strength, is associated with
increased risk of chemotherapy toxicity and poor overall survival in patients
with cancer. The two most important causes giving rise to sarcopenia are poor
nutritional status and chronic inflammation. In fact, poor nutritional status
is frequently associated with loss of appetite, due to early satiety. Moreover,
the chronic inflammatory state often seen in patients with cancer is thought to
be driven by a gut barrier dysfunction (GBD), characterized by breakdown and
leakage of the gut epithelial barrier. These changes in intestinal mucosal
barrier are due to transient disruptions in the microbial composition, a
phenomenon known as dysbiosis. Based on our previous experience, we postulate
that faecal microbiota transplantation (FMT) from obese donors in patients with
cancer can improve satiety (appetite) and subsequently nutritional status.
Secondly, FMT might restore the gut barrier function and hence reduce systemic
inflammatory tone.
Study objective
Primary objective:
Effect of fecal transplantation (from healthy obese donors) on faecel
microbiota composition in relation to satiety (questionnaires, biomarkers) and
metabolism (REE ) in patients with metastasized or locally advanced oesophageal
or gastric cancer receiving standard first-line palliative chemotherapy
(capecitabine and a platinum-containing therapy).
Secondary objectives:
Effect of fecal transplantation on:
1. Sarcopenia (measured by CT-scan).
2. Body composition (BIA)
3. Systemic inflammation and gut barrier function (CRP, plasma interleukins/LPS
binding protein levels and fecal calprotectin) in relation to energy metabolism
as measured by resting energy expenditure (REE).
4. Chemotherapy toxicity, graded with the Common Terminology Criteria for
Adverse Events (CTCAE)11
5. Treatment response measured by CT-scan at baseline and after the first 3
cycles of chemotherapy (week 12).
6. Overall survival (defined as the number of days of survival after PA
diagnosis).
Study design
Double blinded randomized controlled single centre trial.
Patients will be randomized to the following 2 treatment arms:
1. Allogenic (obese donor) fecal transplantation (n=8)
2. Autologous (own) fecal transplantation (n=8)
Intervention
Patients will be treated with infusion of either allogenic or autologous
microbial transplantation by duodenoal tube after bowel lavage. Bowel lavage is
performed by drinking 3-4 liter Klean Prep de evening prior to the fecal
transplantation. De duodenal tube is placed using the Cortraksystem and
abdominal X is performed afterward to check position of the tube in the
duodenum. Meanwhile, fllogenic or autologous feces mixed in 500 cc saline
(filtered, <2 hours after processing) and will be infused in the duodenum
through positioned duodenal tube.
Study burden and risks
Total study duration is 12 weeks, during which subjects will visit the AMC 2
times extra (total duration 4 hours) and in total 200 (20ml screening and 60 ml
blood at 0,4 and 12 weeks). At 0 and 4 weeks, a REE and BIA will be performed.
Also, at baselinge (T=0) faecaltransfusion will be performed. In the last 5
years we have performed over 300 fecal transplantations at the AMC in several
patientgroeps without seeing any short or long term complications
(FANFARE MEC 2013_278, FATLOSE-1 MEC, 07/114; FATLOSE-2 MEC 11/023; FEBALIGO
MEC 2013_090). Although in theory there is always the risk of transferring
(unknown) infectious diseases (just like with bloodtransfusions), however using
a thorough donor screening protocol can minimize this risk.
The total dose equivalent of the participating patients (aged 18-40 years) will
be 0.7mSv for the abdominal X-ray during coretrack resulting in 0.7 mSv for the
whole study (which is less than the currently allowed 10.0 mSv WHO category
IIb). A 3-monthly response evaluation measured by CT-scan is a standard
procedure for this population receiving chemotherapy. Therefore, no additional
imaging for this study is required. Since we feel that this intervention can
help us to improve metabolic dysregulation in patients with metastasized or
locally advanced oesophageal and/or gastric cancer, we believe that the burden
of this study is in line with the potential therapeutic insight that will be
gained.
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
Recipients:
- Male or female with metastasized or locally advanced oesophageal and/or gastric cancer receiving standard first-line palliative chemotherapy (capecitabine and platinum-containing therapy)
- Age >18 years old
- Meeting the criteria for sarcopenia, using computed tomography (CT)-scan: the L3 muscle area surfaces will be normalized for patient height to calculate the L3 muscle index and expressed in cm2/m2. The cutoff values used for sarcopenia are 52.4 cm2/m2 for men and 38.5 cm2/m2 for women, based on the method of Prado et al1
- Meeting the International Classification of Functioning, Disability and Health (ICF), WHO 1, 2 or 3.
- Stable medication use, all subjects use PPI.
- Subjects should be able and willing to give informed consent;Donors:
- Obese otherwise healthy caucasian male or female
- BMI >25 kg/m2
Exclusion criteria
Recipients:
- XTC, amphetamine or cocaine abuse
- Alcohol abuse (>3/day)
- Cholecystectomy
- HIV infection with a CD4 count < 240
- Patients with diabetes mellitus (there are several studies indicating that a high level of NLR may reflect ongoing vascular inflammation and play an important role in the pathophysiology of DM and even prediabetes). ;Donors:
- Presence of chronic low grade inflammation or criteria of metabolic syndrome
- Use of any medication including PPI and antibiotics
- Presence of type 2 diabetes or hypertension
- Diarrhoea
- Cholecystectomy
- HIV, HAV, HBV, HCV, active CMV, active EBV, IBD
- Unsafe sex practice (questionnaire)
- Presence of faecal bacterial pathogens (salmonella, Shigella, Campylobacter, Yersinia), virus (Rotavirus, Noroviru, enterovirus, parechovirus, sapovirus, adenovirus, astrovirus) or parasites
- Positive C. difficile stool test
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL56559.018.16 |