Clinical trial NCT06432608: Efficacy of Lacticaseibacillus Paracasei Strain Shirota on Clinical Manifestation of Functional Constipation in Mexican Adults
Official title: Single Arm Study to Evaluate the Efficacy of Lacticaseibacillus Paracasei Strain Shirota (Formerly Lactobacillus Casei Strain Shirota) Fermented Milk (Yakult®) on the Maintenance of Clinical Manifestations of Functional Constipation in Mexican Adults
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Constipation
Keywords: functional constipation
clinical manifestation
mexican
short fatty acids
Lacticaseibacillus paracasei strain Shirota
Lead sponsor: University of Guadalajara
Sponsor class: OTHER
Collaborators: name: Yakult Honsha Co., LTD
First posted: 2024-05-29
Enrollment: 50
Sex: ALL
Minimum age (years): 20
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Original longitudinal, analytical, and prospective quasi-experimental study in adults diagnosed with functional chronic constipation under the ROME IV criteria. The study will provide a product based on fermented milk with the probiotic Lacticaseibacillus paracasei strain Shirota for 4 weeks.
Primary purpose: TREATMENT

Brief summary: Chronic functional constipation is a gastrointestinal disorder with an approximate prevalence of 14% of the Mexican population, which is characterized by difficult or incomplete defecation and/or infrequent bowel movements, with the absence of symptoms such as abdominal pain or inflammation, and in If they occur, they should not be the predominant symptoms. Its origin is multifactorial and includes variables such as diet, water consumption, alteration in motility, and intestinal microbiota, the latter as a source of different secondary metabolites such as short-chain fatty acids (SCFAs).

Lower SCFA values in constipation would alter the relationship between them, increasing the risk of clinical manifestations of functional chronic constipation. In addition to physical discomfort, subjects with this disease manifest alterations in their quality of life.

Recent studies have suggested using probiotic microorganisms to treat this functional disorder due to their beneficial effects on evacuation frequency, SCFAs, and quality of life. However, in Mexico, knowledge of the above is limited. Therefore, this research aims to determine the effect of consuming a product based on fermented milk with the probiotic Lacticaseibacillus paracasei strain Shirota on the clinical manifestations of functional constipation in Mexican adults and its relationship with SCFAs.

Detailed description: 1. Background

   Constipation is an intestinal disorder characterized by difficulty defecating, infrequent bowel movements, hard or lumpy stools, excessive straining, a feeling of incomplete evacuation, and, in some cases, the use of manual techniques to facilitate evacuation.

   Due to its presentation time, constipation is classified as acute or chronic. The acute one lasts less than a week and is commonly determined by a change in diet and/or lifestyle (low fiber intake, decreased physical activity, stress, going to the bathroom in an unknown place, etc.). For its part, the symptoms of chronic illness have occurred over three to six months. Chronic constipation is among the most common gastrointestinal conditions, usually primary or secondary. The first is a consequence of multiple pathophysiological alterations, such as alteration of colonic regulation, lack of coordination of the neuromuscular apparatus, and dysfunction of the brain-gut axis. In turn, secondary chronic constipation can be caused by drugs, neurological disorders, anatomical processes, or metabolic diseases.

   Chronic constipation is defined "from a clinical point of view, chronic constipation is considered secondary when it is a consequence of metabolic, neurological alterations, structural lesions or medications. When other causes have been excluded, it is considered primary, idiopathic, or functional constipation" (FD).

   1.1. Clinical manifestations

   Chronic constipation is a functional gastrointestinal disorder with a prevalence of 3 to 27%, mainly among women and older adults. Approximately 1 in 6 individuals experience chronic constipation. The Mexican Consensus on chronic constipation mentions a prevalence of 14.4% in Mexicans, while other studies carried out in the country have reported a prevalence between 2.4 and 22.3%.

   This pathology is considered a syndrome with different symptoms that are expressed variably. For this reason, the ROMA (Rome Foundation for Functional Gastrointestinal Problems) criteria have been used to diagnose functional chronic constipation. In 2016, the ROMA criteria updated their guidelines, currently in version IV, and included eight categories: A) esophageal disorders; B) gastroduodenal disorders; C) intestinal disorders; D) gastrointestinal pain of centrally median disorders; E) disorders of the sphincter of Oddi and the gallbladder; F) anorectal disorders; G) functional gastrointestinal disorders of childhood and G) functional gastrointestinal disorders of adolescence. Functional intestinal disorders are defined by these criteria, which allow us to differentiate the symptoms of patients with chronic functional constipation from those with similar clinical conditions, such as irritable bowel syndrome.

   In the ROME IV criteria, chronic functional constipation is a disorder characterized by persistent or incomplete difficult defecation and/or infrequent bowel movements without symptoms such as abdominal pain and/or inflammation or, if present, that are not the predominant symptoms. The Bristol scale supports the criteria in which grades 1 and 2 correspond to constipation and correlate with prolonged intestinal transit.

   1.2. Constipation and short-chain fatty acids

   Chronic constipation is a multifactorial process influenced by diet, stool volume, water content, and intestinal microbiota. In recent years, it has been considered that alterations in the balance of the intestinal microbiota may influence the clinical manifestations of chronic constipation. It has been reported that the intestinal microbiota of constipated patients differs from that of healthy adults and children, with a decrease in the genera Lactobacillus and Bifidobacterium. Studies with gnotobiotic animals and in vitro have suggested that the intestinal microbiota influences intestinal motility, the integrity of the intestinal barrier, the modulation of colonic pH, and the immune or nervous response through the production of short-chain fatty acids: butyrate, propionate, and acetate.

   1.3. Constipation and probiotics

   Patients with constipation usually have a prolonged intestinal transit time compared to healthy subjects, decreasing evacuation frequency and stool consistency. To achieve this, laxatives, dietary fiber supplements, and the prescription of some drugs are used as treatment. However, in recent years, the use of probiotics has been considered due to the impact of their consumption on the intestinal microbiota/metabolites and, in turn, on gastric motility.

   It has been reported that consuming 10\^8 to 3 x 10\^10 CFU per day of specific probiotic strains improves intestinal transit, increases evacuation frequency, and improves symptoms related to constipation. Studies with Lacticaseibacillus paracasei strain Shirota (LcS) in the Chinese population showed improvement in the frequency and consistency of fecal matter and reduced intestinal discomfort. The intake of probiotics improves intestinal transit and increases the levels of organic acids that promote peristalsis. It also increases the Bifidobacterium and Lactobacillus genera, which are usually in lower abundance in constipation. Probiotics could not only directly improve intestinal discomfort but also through the formation of secondary metabolites of the intestinal microbiota, such as short-chain fatty acids.

   Therefore, probiotics such as Lacticaseibacillus paracasei strain Shirota have begun to be studied in murine models and in the Asian population as a non-pharmacological alternative for functional chronic constipation. However, its effect on the Mexican population with constipation requires more evidence, as does the relationship between the intake of probiotics in functional constipation and short-chain fatty acids.
2. General objective:

   To evaluate the efficiency of Lacticaseibacillus paracasei strain Shirota Shirota (formerly Lactobacillus casei strain Shirota) in fermented milk (Yakult®) on the maintenance of the clinical manifestations of functional constipation in Mexican adults.
3. Hypothesis:

   The consumption of a product based on milk fermented with Lacticaseibacillus paracasei strain Shirota, has an effect on the maintenance of the clinical manifestations of functional constipation in Mexican adults.
4. Methodology:

An original longitudinal, analytical, and prospective quasi-experimental study in adults diagnosed with functional chronic constipation under the ROME IV criteria is planned. The study will provide a product based on fermented milk with the probiotic Lacticaseibacillus paracasei strain Shirota for four weeks. Before consuming the product, a baseline analysis of SCFAs will be carried out in fecal matter. As part of the techniques and procedures, height and weight will be measured using the ISAK methodology to obtain the body mass index (BMI). Meanwhile, the clinical manifestations of evacuation frequency and consistency of fecal matter will be evaluated, considering the ROME IV criteria, with visual support from the Bristol and symptom severity scales. The analysis of short-chain fatty acids will be done by gas chromatography, whose signal will be compared with an internal standard.

Eligibility criteria: Inclusion Criteria:

* Men and women between 20 and 60 years old, diagnosed with functional chronic constipation (according to the Rome IV criteria).
* Men and women who have given informed consent.

Exclusion Criteria:

* Constipation due to neurological, pharmacological or organic causes.
* Pregnancy or pregnancy expected within the next month.
* Breastfeeding women.
* Diagnosed pathologies such as: diabetes mellitus, kidney or liver failure, infectious disease, inflammatory disease or any neoplastic disease.
* Use of laxatives within 14 days prior to the start of the intervention.
* Use of antibiotics within 14 days prior to the start of the intervention.
* Diagnosis of cancer in the last three years.
* History of drug and medication abuse.
* Active alcoholism with a daily intake greater than 50 g/day.
* Lactose intolerance.
* Known allergies to any substance in the study product (e.g., cow's milk proteins).
* Any subject who needs manual maneuvers to evacuate feces.
* Anticipated major changes in diet or exercise during the study period.
* Eating disorders.
* Participation in another study with any investigational product within 3 months prior to enrollment.
* Regular Yakult consumers
* Subject who does not have the capacity to consent.

Primary outcomes:
measure: Clinical manifestation of functional constipation
timeFrame: 2 months
Secondary outcomes:
measure: Analysis of short-chain fatty acids
timeFrame: 2 months
measure: Height
timeFrame: 2 months
measure: Body weight
timeFrame: 2 months
measure: Body Mass Index (BMI)
timeFrame: 2 months
Other outcomes:
Locations:
Study officials:
affiliation: University of Guadalajara
name: Ma.Refugio Torres Vitela, PhD
role: PRINCIPAL_INVESTIGATOR
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