Clinical Trial Details
— Status: Recruiting
Administrative data
NCT number |
NCT04874883 |
Other study ID # |
24375713.0.0000.5149 |
Secondary ID |
|
Status |
Recruiting |
Phase |
Phase 4
|
First received |
|
Last updated |
|
Start date |
December 1, 2019 |
Est. completion date |
December 1, 2022 |
Study information
Verified date |
April 2021 |
Source |
Federal University of Minas Gerais |
Contact |
Maria Isabel Toulsson Davisson Correia, Doctor |
Phone |
31991688239 |
Email |
isabel_correia[@]uol.com.br |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
Due to the high incidence, cancer and the concomitant presence of malnutrition are currently
a worldwide public health problem. The loss of weight and body tissues is a common condition
in cancer patients with lesions of the airways and digestive tract and is related to anorexia
and the presence and duration of gastrointestinal symptoms, such as diarrhea. The latter
directly interferes with the progression of enteral diets, which are administered in order to
provide adequate nutritional support for the recovery of patients and nutritional status. In
this sense, the importance of measures to help reduce diarrhea episodes is reinforced, aiming
at the adequate infusion of enteral diets and, consequently, nutritional needs. It is known
that the use of antimicrobials is closely related to the increased incidence of nasocomial
diarrhea, as it facilitates colonization by pathogenic bacteria, such as Clostridium
difficile. In addition, nosocomial diarrhea is a very relevant occurrence due to the
financial burden it causes for the hospital institution, which can also worsen the patient's
clinical condition, since he is weakened due to the underlying disease. Despite these
important aspects, studies carried out with the aim of reducing diarrhea episodes in patients
with airway and digestive lesions are still not described in the literature. In this context,
the use of symbiotics presents itself as a possibly beneficial alternative, considering the
role of probiotics and prebiotics in the modulation of intestinal function. In this sense,
this work aims to evaluate the impact of perioperative supplementation with symbiotic on
clinical outcomes and intestinal function of patients with colon cancer and digestive airways
undergoing colorectal resection. It is assumed that the use of symbiotics could have better
results than the use of probiotics and isolated prebiotics.
Description:
Most cancer patients have a compromised nutritional status, 80% are malnourished at the time
of the initial diagnosis. It is known that in patients with airway and digestive cancer the
risk of malnutrition is increased, due to changes caused by the location of the tumor such as
dysphagia, odynophagia and changes in taste.
The clinical effects of malnutrition are manifested by difficulty in healing after surgery,
increased risk of infection and treatment toxicity, in addition to greater demand for care
and hospital costs. Therefore, it is of utmost importance to provide adequate nutritional
needs to these patients, since adequate nutritional therapy (NT) is able to improve their
clinical response and prognosis.
Nutritional support is seen as an important strategy for the treatment and recovery of these
patients, since it promotes greater adequacy of nutritional support, improving nutritional
status as well as response to treatment and immune function, in addition to improving quality
of life and reducing hospital costs. However, gastrointestinal complications, such as
diarrhea, represent important causes for not receiving the planned enteral diet volume, or
the patient's intake inadequacy, which causes an insufficient supply of calories, proteins,
vitamins and minerals over the days, contributing with worsening nutritional status, as well
as increased hospital stay and costs with hospitalization.
Diarrhea affects about 16% to 63% of patients on enteral nutrition. The most frequent causes
of diarrhea in cancer patients are related to medications, such as antibiotics, antacids with
magnesium, lactulose, laxatives, supplements with potassium and phosphorus and medications
with sorbitol6. Other possible causes of diarrhea include hypoalbuminemia, rapid infusion and
intolerance to some component of the diet, infectious causes such as the presence of
Clostridium difficile, severe malnutrition and, more rarely with the use of industrialized
diets, bacterial contamination of the enteral formula.
In particular, the presence of nosocomial diarrhea - defined as infectious diarrhea acquired
in a hospital environment - increases the length of stay of patients (eight days, on
average), increases the likelihood of infections in surgical wounds, and consequently,
hospital mortality. Among the identifiable causes of this type of diarrhea, the
indiscriminate use of antimicrobials has been identified as an important predisposing factor,
particularly in facilitating colonization and intestinal infection by Clostridium difficile.
This bacterium has an incidence between 5% and 39%, with an increased incidence in
hospitalized post-surgical patients.
Thus, it is necessary to study strategies that reduce the incidence of diarrhea in these
patients. In this context, the use of probiotics and prebiotics seems to be an effective
alternative, since the therapeutic effect in the treatment and prevention of intestinal
diseases has been extensively researched.
Probiotics are live microorganisms that, when consumed in adequate and sufficient quantities,
confer benefits to the health of the host. In addition, they compete with pathogenic bacteria
for space and nutrients, blocking their effects and binding them to the intestinal mucosa.
They produce antibacterial substances (bacteriocins), acidify the intestinal pH by
fermentation and production of lactic acid, stimulate the production of mucin and increase
the production and secretion of immunoglobulin A (sIgA). There is evidence that probiotics
also contribute to the reduction of inflammatory mediators such as tumor necrosis factor
(TNF) and growth transformation factor (TGF-β) that modulate the inflammatory response and
favor immune balance. Lactobacillus casei, Lactobacillus rhamnosus, Lactobacillus acidophilus
and Bifidobacterium are some of the probiotics that have benefits described in the
literature.
Cimperman et al (2011), in a pilot study, double masked, controlled placebo evaluated the
effect of treatment with probiotics in patients using antibiotics. The results showed that
the administration of the probiotic Lactobacillus reuteri significantly reduced diarrhea
compared to patients who received a placebo. Still, D'Souza et al (2002), Cremonini et al
(2002) & McFarland (2006) concluded through meta-analyzes that the use of probiotics is
associated with the prevention of diarrhea associated with the use of antibiotics in
hospitalized patients.
Prebiotics are defined as food substances that, when ingested, are not digested and absorbed
by the small intestine. When they reach the colon, they are used as a substrate for
probiotics, selectively stimulating the growth of the intestinal microbiota in addition to
producing short-chain fatty acids (SCFA) that are substrates for colonocytes. SCFAs also
modulate the intestinal microbiota, maintain metabolism and promote a decrease in intestinal
pH, thereby inhibiting the development of pathogenic microorganisms. Rushdi, Pichard & Khater
(2004) evaluated in a prospective, double-masked controlled study the effect of adding
soluble fiber to the enteral diet of patients hospitalized with diarrhea. Patients were
randomly divided into two groups: control (enteral diet without soluble fiber) and treated
(enteral diet with soluble fiber). The results showed a reduction in diarrhea episodes in the
study patients, suggesting the prebiotic benefit of soluble fiber. Examples of prebiotics are
fructooligosaccharides (FOS) and galactooligosaccharides (GOS).
These findings propose that interventions aimed at modulating intestinal function related to
the prevention and control of diarrhea in cancer patients in the postoperative period deserve
to be implemented and evaluated. However, these trials used different probiotic organisms,
prebiotics, doses, duration of treatment and target audience, providing low reproducibility
of the results. In addition, some studies have shown that symbiotics (defined as a
combination of probiotics and prebiotics) can optimize the beneficial results in relation to
the isolated use of probiotics in terms of modulating the immune system and the intestinal
microbiota. It is suggested that under the action of symbiotics there will be better control
of intestinal functioning and improved prognosis.
In this sense, evaluating the symbiotic administration in patients with colon, upper airway
and digestive cancer undergoing surgical treatment would be a potentially beneficial
alternative to be studied, since the consumption of this food component could lead to
modulation of intestinal function, preventing diarrhea that, according to our data, occurs in
30% of the patients hospitalized at the Alfa Institute of Gastroenterology at UFMG.
General objective
To evaluate the impact of the symbiotic on the intestinal function of patients with malignant
neoplasm of the colon, upper airways and digestive tract submitted to surgical treatment.
Specific objectives
- Assess the incidence of diarrhea in the study group;
- Identify other gastrointestinal symptoms such as stasis, vomiting, bloating;
- Identify and monitor the evolution of the nutritional status of patients through
subjective global assessment, anthropometry and food consumption;
- Track postoperative complications, in general.
The study will be carried out at the Alfa Institute of Gastroenterology, Hospital das
Clínicas, Federal University of Minas Gerais, located in Belo Horizonte, Minas Gerais.The
sample will comprise 42 patients (21 in the intervention group and 21 in the control group).
The sample calculation was performed according to Hulley et al. (2001), using the proportion
of 30% improvement in the symptom of diarrhea with the use of symbiotic from the average of
other studies, considering a range of 45% of the confidence interval (difference between the
highest and the lowest value found) and 12% loss with the intervention, also observed in the
reference studies. Individuals will be invited to participate in the study and will have a
detailed explanation of the procedure and research in which they will be inserted, and must
sign a free and informed consent form. Individuals who have inflammatory bowel diseases will
be excluded; have previously undergone operations on the gastrointestinal tract; have used
antibiotics, prebiotics, probiotics or symbiotics in the last 15 days and are using an
enteral fiber diet. The study will be double-masked and the individuals will be randomly
divided into two groups: Symbiotic group (S) - will receive the symbiotic (association of
fructooligosaccharide, prebiotic, and four probiotic strains: Lactobacillus casei,
Lactobacillus rhamnosus, Lactobacillus Acidophilus, and Bifidobacterium bifidum) enterally or
orally in the amount of a sachet, twice a day. Control Group (C) will receive maltodextrin
placebo (carbohydrate easily absorbed and digested, not fermented by colonic bacteria and
which does not interfere in the microbial ecology of the gastrointestinal tract or in the
metabolism and function of the intestine), either enterally or orally in a sachet. hours
until hospital discharge. Personal information such as full name, medical record number, sex,
age, marital status, origin, date of birth and hospitalization will be collected for patient
identification. Information regarding the location of the tumor, type of tumor, age of
diagnosis in years and months, type of previous and current treatment (surgical, radiotherapy
and / or chemotherapy) use of antibiotics, comorbidities and presence or not of infection
will be collected from the medical record . The evaluation of intestinal functioning will be
made by direct questioning to patients and family members, as well as the nursing records.
The occurrence or not of diarrhea (defined as more than three bowel movements / day),
frequency and volume, whether or not gastrointestinal symptoms such as distension and
abdominal pain during hospitalization will be assessed. Nutritional assessment will be
carried out by Subjective Global Assessment proposed by Detsky (1987) and using
anthropometric parameters: current weight, height, arm, tricipital skin fold, subscapular and
biochemical.
The start of the diet in the postoperative period and the nutrient supply will be verified
through the analysis of food consumption and / or infusion of the enteral diet, which was
calculated according to the service protocol, contemplating 30 calories per kilogram of
current weight.
Complications will be assessed through the daily assessment of the patient and medical
records and classified according to the proposal by Dindo (2004).