This intervention study aims to investigate the effects of daily administration of a prebiotic fiber mixture in a Nutritionally Complete Oral Nutritional Supplement (ONS) for 8-9 weeks on intestinal microbiota composition and diversity in patients…
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Source
Brief title
Condition
- Gastrointestinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main endpoints of this intervention study are the differences (*baseline vs
post-intervention) in shifts of overall intestinal microbiota composition,
intestinal microbiota diversity, and relative abundance of specific microbial
taxa (e.g. Bifidobacterium) between the test group and control group. Based on
interventions with prebiotic fibers in other populations published in the
literature, and taking the variation seen in the initial analysis of our
ongoing observational studies into account, we performed a preliminary power
calculation. We expect to enroll a total of 62 patients with advanced
colorectal cancer, 31 patients in the test group and 31 patients in the control
group. This sample size is deemed necessary to ensure sufficient statistical
power to observe the effects of the prebiotic fibers.
Secondary outcome
As exploratory objectives, this study will assess: (1) The feasibility,
tolerance, and compliance of a nutritional intervention with a prebiotic ONS in
patients with advanced CRC, (2) the effects of the prebiotic ONS on fecal and
blood parameters, tumor response, chemotherapy toxicity as well as the
metabolic phenotype (e.g. body weight, body composition, inflammatory profile),
and (3) the consequences for the patient-reported QoL and physical functioning
compared to a control ONS.
Background summary
Colorectal cancer (CRC) is the third most common cancer in the world. In the
case of advanced CRC, the standard systemic treatment is often based on
fluoropyrimidines, such as 5-fluorouracil (5-FU). 5-FU treatment has two
significant drawbacks; (1) a limited proportion of patients respond to
treatment, and (2) about 80% of patients experience some form of toxicity. The
intestinal microbiota has been shown to modulate both and might be of influence
on chemotherapy efficacy, toxicity, and quality of life (QoL). Our clinical
studies and pre-clinical studies from other research groups demonstrated that
intestinal bacteria and their metabolites are affected by chemotherapy and
potentially influence treatment outcomes. In the context of the care for cancer
patients, prebiotics are a promising strategy for intestinal microbiota
modulation since they are a non-invasive and patient-friendly method to induce
intestinal microbiota changes, without containing living microorganisms (in
contrast to probiotics). It can therefore be concluded that targeted modulation
of the intestinal microbiota with prebiotics has the potential to optimize
5-FU-based chemotherapy.
Study objective
This intervention study aims to investigate the effects of daily administration
of a prebiotic fiber mixture in a Nutritionally Complete Oral Nutritional
Supplement (ONS) for 8-9 weeks on intestinal microbiota composition and
diversity in patients with advanced CRC treated with 5-FU-based chemotherapy
compared to a control ONS. As secondary objectives, this study will assess (1)
the feasibility, tolerance, safety, and compliance of a nutritional
intervention with prebiotics in patients with advanced CRC, (2) the effects of
the intervention on fecal and blood parameters, tumor response, chemotherapy
toxicity as well as the metabolic phenotype (e.g. body weight, body
composition, inflammatory profile), and (3) the consequences on the
patient-reported QoL and physical functioning.
Study design
This intervention study is a double-blind randomized (1:1) controlled trial
that will be performed in the Maastricht UMC+. The duration of the intervention
phase for each subject will be approximately 8-9 weeks depending on the study
product intake start date, chemotherapy regime schedule, and the potential
occurrence of an interruption or delay in chemotherapy.
Intervention
Patients will be stratified based on their assigned chemotherapy regimen before
randomization (FOLFOX, CAPOX, and CAP). Following stratification, patients will
undergo a 1:1 block randomization. Patients will be randomized to either the
test group (ONS enriched with prebiotic fibers) or the control group
(isocaloric, isonitrogenous ONS without prebiotic fibers). Patients will start
with the prebiotic or control ONS as soon as possible, but we aim to target
minimally three days before the start of the 5-FU-based treatment. Patients
will take the prebiotic or control ONS two times a day during four cycles of
FOLFOX or three cycles of CAPOX or CAP chemotherapy.
Study burden and risks
During the study period, patients are required to collect multiple fecal
samples at their homes and complete several questionnaires. The FQ18
questionnaire, which is to be filled out only once at the beginning of the
study, will take approximately 30 minutes to complete. This questionnaire is
more comprehensive than the others. The other questionnaires take approximately
15 minutes to complete.
Collecting fecal samples is designed to be an easy and hygienic process that
patients can manage in the comfort of their own homes. To minimize
inconvenience for the patients, every research appointment will be scheduled to
coincide with their regular hospital visits if possible. Furthermore, blood
samples for the study will be drawn, if possible, simultaneously with the
routine blood tests that are required before each treatment cycle. The test and
control ONS will be provided in small bottles of 125ml to minimize the burden
for the participants. To accommodate individual preferences and enhance
compliance, patients will have the option to choose between two flavors:
vanilla or strawberry.
P. Debeyelaan 25
Maastricht 6229HX
NL
P. Debeyelaan 25
Maastricht 6229HX
NL
Listed location countries
Age
Inclusion criteria
To be eligible to participate in this study, a subject must meet all of the
following criteria:
- Patients diagnosed with advanced CRC who will be treated with 5-FU-based
therapy (FOLFOX, CAPOX, capecitabine monotherapy)
- Simultaneous treatment with bevacizumab, panitumumab or cetuximab is allowed,
provided that no systemic antibiotics are used (topical antibiotics are
allowed).
- Proficient use of the Dutch language
- The patient is older than 18 years of age
- Performance (ECOG/WHO) score 0-2
- Written informed consent
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded
from participation in this study:
- Microsatellite instability (MSI) or deficient mismatch repair (MMR) proteins
- Abnormal DPYD and/or reduced DPD enzyme function
- Presence of ileostomy
- Pregnant or nursing
- Previous systemic therapy for advanced CRC. If the patient received prior
(neo)adjuvant systemic therapy, it must have been completed at least 6 months
before the diagnosis of the advanced disease
- Therapeutic systemic antibiotics used less than one month before the start of
the 5-FU-based treatment (topical antibiotics are allowed)
- Abdominal radiotherapy less than two weeks before the start of the 5-FU-based
therapy
- Simultaneous use of other pro- and/or prebiotics during the study period (see
the example list in appendix E in *E1 E2. Informatiebrief en
toestemmingsformulier proefpersonen*)
- Inflammatory bowel disease (Crohn's disease or ulcerative colitis)
- Simultaneous treatment with irinotecan-based therapy
- Known allergy to any ingredients present in the test or control ONS,
requiring a fibre-free diet or suffering galactosemia or lactose intolerance
- Simultaneous participation in another medical-scientific intervention study
- Physically or mentally incapable or incompetent
- All conditions that, in the opinion of the physician, are not suitable for
participation in this study (e.g. severe renal failure).
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 | NL86537.068.24 |