Clinical trial NCT04716868: Evaluation of a Supplement of Agave Tequilana Weber Azul vs Psyllium Plantago in Patients With Functional Constipation
Official title: Prospective, Randomized and Controlled Study for the Evaluation of the Effectiveness of a Supplement of Agave Tequilana Weber Var. Azul Fiber Derivatives vs Psyllium Plantago in Patients With Functional Constipation
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Functional Constipation
Keywords: Functional constipation
Agave tequilana Weber var. Azul
Psyllium plantago
Microbiota
Lead sponsor: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Sponsor class: OTHER
First posted: 2021-01-20
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: a prospective, randomized, controlled and single blind study to determine the efficacy of the blue agave Tequilana Weber fructans intake in subjects with functional constipation.
Primary purpose: TREATMENT

Brief summary: Introduction: Constipation is one of the gastrointestinal disorders MOST frequent That Affects around 20% of the western population, being more frequent in the female gender (M1.5: H1). Constipation can be primary, When causes constipation associated With (medication, mechanical obstruction, spinal cord injury, etc.) and secondary. There are multiple therapeutic options for the management of constipation, changes in lifestyle Including, the intake of fiber, laxatives and pharmacological treatment and in selected cases (colonic inertia) surgery. The first option in the therapeutic management for Patients With constipation are changes in lifestyle, Among Which is the type of diet (increase in fiber intake, Which Has Been Associated With an improvement in the fecal matter and the evacuation frequency), liquid intake and exercise. Aim: To Evaluate the efficacy of the blue agave fructans Tequilana Weber in Patients With functional constipation Methods: This is a prospective, randomized, controlled and single blind study to determine the phase III efficacy of the blue agave fructans Tequilana Weber intake in subjects with functional constipation. In order to Achieve so, it is planned to include over 18 years of Patients age Fulfill the WHO as well as inclusion criteria The Rome III criteria for functional constipation. Statistical analysis plan: The data obtained will be analyzed with SPSS version 24. For continuous variables the results are presented in mean ± standard deviation when the variables are normally distributed or medians and percentiles otherwise and as frequency and percentages when they were categorical. For basal and subsequent comparison to the intra intervention groups, Student's t-test for paired samples (variables with normal distribution) or the Mann-Whitney U (variables without normal distribution) is used in the case of continuous variables and X2 or the McNemar test in the case of categorical variables. For comparison between groups ANOVA (variables with normal distribution) or Kruskal-Wallis (non-normal distribution variables) used for continuous variables and the same percentage of change obtained when the variables are continuous. Also an analysis of covariance (ANCOVA) was performed to control variables that might have an effect on the response variables.

Detailed description: This is a prospective, randomized, controlled and single blind study to determine the phase III efficacy of the blue agave fructans Tequilana Weber intake in subjects with functional constipation.

In order to Achieve so, it is planned to include over 18 years of Patients age Fulfill the WHO as well as inclusion criteria The Rome III criteria for functional constipation. (See table below).

The phase of our study is designated based on article 66 of chapter II "On Pharmacological Research" of the Regulation of the General Law on Health in Research That defines PHASE III studies Follows as: It is the administration of a research drug to large groups of Patients (Usually external), to define ITS therapeutic utility and identification identify adverse reactions, interactions and external factors That May alter the pharmacological effect.

Patients of the institute will be called after invitations to Participate in Placing a protocol for Patients With constipation. Patients Who Have Not Been registered and meet the inclusion criteria May Also Participate.

The study to be Carried out will be Explained and read and, where appropriate', the informed consent will be signed by the Patient During the initial visit (Visit 1) of eligibility, Where the subject will be Given 2 questionnaires (see annexes), one They meet to determine if the ROME III criteria for functional constipation (FC) and another to ASSESS if the patient does not meet the criteria for irritable ROME III bowel syndrome (IBS) and a baseline breath test will be performed.

In Addition, the previous use of fiber supplements and laxatives, which must be suspended at Least 2 months prior to randomization, will be EVALUATED.

The subject will return to a second visit (Visit 2) (Which will depend on Whether the patient is taking laxatives or fiber supplements) for a complete physical evaluation and the fiber intake diary will be Assessed to determine the amount of fiber intake in the diet as well as the diary of evacuations and the SmartPill © will be Given and That way, the patient will return to the hospital to register the data after the capsule Having evacuated.

The patient will return a week later (Visit 3) on a 12 hour fast, the fiber intake and the evacuation diaries will be re-EVALUATED and will be EVALUATED They again by a nutritionist. A new breath test will be Carried out. The subject will be Asked to complete the SF-36 Quality of Life Questionnaire. A stool sample will be Collected for ITS analysis in Addition to a blood sample for determination of fasting glucose, glycosylated hemoglobin A1c, Insulin and full lipid profile.

The subjects will be randomized to receive one of four treatments That can be Psyllium plantago 15g, blue agave Tequilana Weber fructans at doses of 5, 10g and blue agave Tequilana Weber fructans at a dose of 5 g + 10 g excipient for a concentration of 33 % of blue agave fructans Tequilana Weber.

The randomization will be computer-generated with a participation number and the assignment of the treatment will be consecutive.

The product will be supplied in identical bottles With the same amount of powder in a container That will only be identifiable With the name of the protocol as well as the patient's number.

The patient will be provided with a measuring spoon to administer the amount of product Necessary for each of the doses (5, 10 and 15g respectively) or with envelopes Containing the exact Amounts Weighed.

The patient will be instructed to keep a diary of the diet, of the evacuations and a sheet to ASSESS adverse effects. The subject will return (Visit 4) at the end of a month ± 5 days on a 12 hour fast and Their adherence will be Assessed by product weight in the container subtracting the number of grams required daily ACCORDING TO the assignment of treatment.

The fiber intake diaries will be EVALUATED again by the nutritionist, the evacuation will Also be EVALUATED diary. A medical evaluation will be Carried out That includes questioning and physical evaluation. Subsequently, a blood sample will be to determine fasting glucose Obtained, glycosylated hemoglobin A1c, insulin and lipid profile and a full sample of excrement will be Obtained and SmartPill® will be Given.

The patient will Continue with the supplement in the same container and will be scheduled for a month later. In the end-of-treatment visit visit (visit 5), the fiber will be EVALUATED journals consumption again by a nutritionist and the evacuation will be EVALUATED diary as well.

A medical evaluation will be Carried out That includes questioning and physical evaluation and Their adherence will be Assessed by weighing the product in the container, subtracting the number of grams That it requires daily ACCORDING to the treatment assignment or delivery by the patient of the empty envelopes used.

Subsequently, a blood sample will be to determine fasting glucose Obtained, glycosylated hemoglobin A1c, insulin and lipid profile and a full sample will be Collected stool and breath test at the end will be Carried out.

For end of the visit, Which Will Be Carried out one month after stopping the treatment, the evacuation will be EVALUATED diary and a stool sample will be Collected and with it the intervention in the part of the study will end. Total The follow-up duration for each patient will be 3 months, enough time to observe and compare the effect of the fibers to be used. It is Important to mention That in recent studies Carried out by the same team and with blue agave Tequilana Weber fructans, effects on intestinal transit Have Been observed from the first week of intake, in fact this is one of the Reasons to focus the study on functional constipation and intestinal transit.

Breath test:

A breath test will be Carried out in order to measure hydrogen and methane Concentrations previously Exhaled In Patients randomized in visits 1 and 5.

In order to carry out the breath test gas chromatography equipment will be used, brand Quintron® Breath-tracker.

For That, The Patients will be Asked:

* Not to take antibiotics prior weeks At least to the test.
* Stop the intake of food rich in fibers and starches 24 h before the test.
* Not to take alcohol, or smoke
* Have a minimum of 8 hours fasting
* Perform oral hygiene before starting the test and during the performance of measurements.

This test lasts 3 hours, during which the patient can not leave the laboratory facilities motility, can not speak too much or sleep. Exhaled air samples are taken every 15 minutes during this period.

SmartPill®:

SmartPill® test will be conducted on visits 2 and 4.

Colonoscopy:

Is a tool which will be subject to scrutiny patients ≥55 years with newly diagnosed constipation or those where changes in bowel habits observed in this age group. This fundamental objective, rule out potentially serious diseases and not to delay the diagnosis of these during the research study. one colonoscopic study all patients who have constipation and any of the following characteristics will be used:

1. Diagnosis of constipation less than 1 year
2. Subjects ≥55 years who do not have colonoscopic evaluation in the last 3 years prior to study entry
3. Chronic but with alarm data (: Unexplained weight loss, recent transrectal bleeding \<6 months, recent changes in the defecation pattern example) Constipation

Patients include:

Studies with fiber supplements (Psyllium, Plums8) Have included 25 to 30 patients per group to find differences between groups.

In total it is planned to include 60 patients randomized as follows: 15 patients receive fructans blue agave Tequilana Weber dose of 5 g, 15 patients received the dose of 10 g, 15 patients received the dose of 5g of agave fructans blue Tequilana Weber + 10 g excipient and 15 patients received 15 g plantago psyllium.

Gas Chromatography: (determination of short-chain fatty acid AGCC)

AGCC for determining ion detector flame will be used. The following steps are performed:

1. 50 uL ethyl butyrate is added to 1 g of faeces
2. 1 mL of hydrochloric acid was be added.
3. It is centrifuged at 3000 g for 10 minutes. The supernatant was removed.
4. Subsequently it is added 300 uL N-Methyl dibutil sililtrifluoroacetamide (MTBSTFA).
5. solution at 80 ° C for 20 min heat up.
6. It left undisturbed at room temperature for 24 hrs to ensure complete derivatization of lactic acid.
7. analyzing samples by gas chromatography according to method developed for specific samples will be performed.

Extraction of DNA from faeces, PCR amplification and bacterial 16S rRNA sequencing:

RRNA sequencing is the method of choice to determine high taxonomic relationships (gender up level). Because the 16S rRNA molecule contains highly variable regions, it is usually possible to find regions 20 to 30 bases that are completely unique to a single species of bacteria.

To perform the analysis, will collect in fecal specimens are sterile plastic containers. Immediately after collection, the samples will be transported to the laboratory in ice bucket 2 to 8 and then frozen at -73 ° C until processing.

DNA extraction was carried out following the instructions of the automated method NucliSENS® easyMAG® (BioMerieux, Durham, NC, USA) with a brief initial modification before automated process. Is weighed and suspended 200 mg of fecal matter of each sample in 0.3 mL of phosphate buffered saline solution-(8 mM Na2HPO4, 137 mM NaCl, 2.7 mM KCl, 1.5 mM KH2PO4 and) vigorous agitation for 30 seconds. 100 .mu.l of the suspension was placed in boiling 15 min and immediately frozen at 0 ° C on ice. Bacterial homogenate was centrifuged at 13,000 g for 10 min and the supernatant will be collected in tubes 500 .mu.l.

This specimen will be used for the isolation of DNA on automated equipment. PCR amplification real time 16S rRNA bacterial be carried out as described by previous reports using a Light Cycler-(Roche) equipment.

Quantification of bacterial phyla in major categories described: 1) Firmicutes, 2) Bacteroidetes, 3) Actinobacterias, 4) Proteobacteria. It will be conducted by the method of quantitative PCR in real time using the primers and conditions described previously, pR amplify specific fragments of bacterial 16S rRNA population groups described. We will use primers called barcode 967 F (CNACGCGAAGAACCTTANC) and 1046R (CGACAGCCATGCANCACCT) to amplify the 16S rRNA fragments V6 bacterial V6.

Sequencing and analysis of the amplified fragments is by fluorescent sequencing equipment terminator 3130 / genetic analyzer (Applied Biosystems).

The PCR products were sequenced and analyzed and will be submitted to GenBank for species identification.

Extracting bacterial DNA and quantitation of bacterial species used to demonstrate the prebiotic effect of agave fiber, since selective growth of the population of bifidobacteria and lactobacilli and occurrence of short-chain fatty acid in stool is expected.

Thus in addition to the functional properties and their effects on constipation, you may check the prebiotic effect of agave fructans.

Eligibility criteria: Inclusion Criteria:

* Patients over 18 years old.
* functional constipation ROME III criteria as
* Subjects ≥55 years with recent colonoscopy (\<3 years)

Exclusion Criteria:

* Taking supplements of fiber in the last 2 months
* Stimulant laxatives consumption chronically (Senna, Bisacodyl)
* decompensated comorbidities (example: uncontrolled diabetes mellitus HbA1c\> 9%, decompensated Organ failure, decompensated hypertension (untreated or TA\> 160 mmHg systolic and 95 mmHg diastolic)
* Using digital maneuvers or enemas to achieve evacuation
* Personal history of active or previous cancer
* abdominal surgery (except appendectomy, cholecystectomy, hysterectomy)
* Presence of alarm data in the last 6 months (trans-rectal bleeding, unexplained weight loss, abdominal pain)
* Use of drugs known promote constipation (opioid derivatives, calcium channel blockers, anticholinergics tricyclic antidepressants type)
* Prostration (immobility or poor mobility)
* Diseases such as untreated hypothyroidism with hormone replacement, and diseases associated with hypercalcemia that promote constipation
* Other causes of secondary constipation
* Meet criteria for constipation predominant irritable bowel
* Pregnancy.

Primary outcomes:
measure: An increase of more than one complete evacuation from basal spontaneous from baseline at the end of active
timeFrame: 15 days
Secondary outcomes:
measure: Change in the classification of Bristol
timeFrame: 15 days
measure: Effect of supplementation of fructan Weber blue agave Tequilana in the frequency of bowel movements
timeFrame: 15 days
measure: Evaluate the impact of the concentration of short-chain fatty acid, particularly butyrate, in the feces of subjects before and after addition of fructans Tequilana Weber blue agave.
timeFrame: 8 weeks
measure: IV. Evaluate the impact of supplementation fructans Weber blue agave Tequilana the microbiota
timeFrame: 8 weeks
measure: V. To evaluate the impact of serum glucose concentration and HbA1c fasting serum of subjects before and after addition of fructans Tequilana Weber blue agave
timeFrame: 8 weeks
Other outcomes:
Locations:
city: México
country: Mexico
facility: National Institute of Medical Sciences and Nutrition Salvador Zubiran
state: Cdmx
Study officials:
affiliation: National Institute of Medical Sciences and Nutrition, Salvador Zubiran
name: Enrique Coss-Adame
role: PRINCIPAL_INVESTIGATOR
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