Clinical trial NCT03117322: Synbiotic, Prebiotics and Probiotics in Children With Cerebral Palsy and Constipation
Official title: Efficacy of the Supplementation With a Symbiotic, a Prebiotic and a Probiotic to Produce a Beneficial Effect on the Intestinal Microbiota and on the Characteristics of Feces in Children With Cerebral Palsy (CP) and Chronic Constipation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Cerebral Palsy
Chronic Constipation
Keywords: cerebral palsy
children
chronic constipation
synbiotic
prebiotics
probiotics
agave inulin
microbiota
Lead sponsor: Hospital Civil Juan I. Menchaca
Sponsor class: OTHER
First posted: 2017-04-17
Enrollment: 40
Sex: ALL
Minimum age (years): 6
Maximum age (years): 60
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: Three interventions in parallel against a control group
Primary purpose: TREATMENT

Brief summary: Randomized double blind controlled clinical trial. Participants will be enrolled at the New Civil Hospital of Guadalajara "Dr. Juan I. Menchaca" during the period from May 2017 to July 2018, from six to 59 months of either sex. The duration of each participant in the study will be of four weeks. Each participant will be randomized assigned to any of the different study groups: synbiotic, prebiotic, probiotic or placebo. Hypothesis: The efficacy of supplementation with a symbiotic, a prebiotic and a probiotic differs in its beneficial effect on the intestinal microbiota and the characteristics of feces in children with CP and chronic constipation.

Detailed description: All the data registered in the case report forms will be monitored by the responsible party. This person will be monitoring each procedure during the study.

All the data in the case report forms will be obtained from the information obtained from the legal caregiver or the parents of the child and/or from the medical and electronic records and calls to the parents or legal caregivers and will be introduced daily in the Statistical Package for the Social Scienses (SPSS) program version 21. The responsible party will have access to this database and will verify the information.

Plan for missing data. In case that we have some missing variables, we will call the parents or legal caregiver of the children if it is about the data of the child. In case of missing data, unavailable or non-reported variable and it is not possible to compare the initial vs final phases, the subject will be excluded from the study. In case of finding an out-of-range laboratory results we will repeat the test. If we have some missing data from the subject but we can analyze other results from the same subject, it will not be excluded.

Standard Operating Procedures to address registry operations and analysis activities, such as patient recruitment, data collection, data management, data analysis, reporting for adverse events, and change management. Patients will be recruited from the nutrition and neurology outpatient at the New Hospital Civil of Guadalajara. We will apply a standardized questionnaire to the parents or legal caregivers to assure that the subject could be eligible to the study. Once all the inclusion criteria are fulfilled then another questionnaire or case report form will be filled. The informed consent will be explained and given to the parents or legal caregivers of the child for sign. An external person will be chose to assign randomly (by envelops) the subjects to each group. This person will provide the study product and the diaries to the parents or legal caregivers. Data from the case reports forms will be captured by the principal investigator and monitored by the responsible party. Te adverse events will be reported by phone calls during the four weeks (two to three phone calls in a week). To analyze the information, the SPSS program version 21 will be used.

Sample size. The sample size was calculated according to the next formula:

n= K (σ12 + σ22)/ (μ1 - μ2) 2 = 6.2 (1.12 + 0.62)/ (4.01 - 2.8) n= 7 + 3 (30% probability of exclusion) = 10 children for each group, total subjects in the study: 40.

α= 0.05 β= 0.20 Data was obtained from the study of Indrio F, et al (2014) 18 with the number of evacuation.

Sampling system. Simple random sample by means of closed envelopes with a figure inside. We will have 40 envelopes closed, 10 of them will have a circle, 10 a triangle, 10 a star and 10 a heart. They will be put into a box; this will be rotated five times before taking an envelope. Randomly, a person outside the study will take an envelope, will see the chosen figure and will write it down in the register.

Statistical analysis. First stage. Shapiro Wilk test will be performed to see the distribution of the data. Descriptive statistics: mean, standard deviation, percentages and frequencies will be performed. Second stage. Analytical statistics: Intra-groups: Student's T test for dependent samples for parametric data or the Wilcoxon test for non-parametric data. Chi square for analysis of qualitative data. Inter-groups: One-way ANOVA with post hoc (Bonferroni) tests. If the data are not parametric, Kruskal-Wallis and if it is significant, Mann Whitney's U will be performed as post hoc. Third stage. Linear regression and logistic regression will be performed.

Ethical considerations. Parents or legal representatives of the child will be informed about the study, requesting their signature for consent. Human research guidelines will be respected according to "good clinical practice". The protocol will be submitted to the Bioethics Committee of the New Civil Hospital of Guadalajara and the University of Guadalajara. Care will be taken to respect the recommendations of the Helsinki Declaration in its last correction made during the 64th Annual Assembly organized by the World Medical Association (2013).

Eligibility criteria: Inclusion Criteria:

* Participants attending the outpatient of nutrition and/or pediatric neurology with cerebral palsy diagnosed and confirmed by a pediatric neurologist, and that belong to levels IV or V of the Gross Motor Function Classification System (GMFCS).
* Participants with constipation according to the Rome IV criteria.
* Signed informed consent by one of the child's parents or legal guardians

Exclusion Criteria:

* Refusal to continue in the study
* Use of antibiotics during the study, consumption of laxatives, food fibers, lactulose, magnesia or products containing probiotics, prebiotics or both as infant formulas (NOTE: Glycerin suppositories will only be allowed when there is no evacuation for more than five days).
* Omission of administration of the required dose of symbiotic, prebiotic, probiotic or placebo and/or administered with an unspecified frequency (compliance \<95%)
* Adverse effects not related to the agent of study.

Primary outcomes:
measure: Change in the composition of the microbiota (firmicutes, bifidobacteria and lactobacilli)
timeFrame: change from baseline bacteria composition at four weeks
measure: change in consistency of feces
timeFrame: change from baseline consistency at four weeks
measure: change in potential of hydrogen (pH) of feces
timeFrame: Change from baseline pH at four weeks
measure: change in frequency of evacuations
timeFrame: change from baseline frequency at four weeks
Secondary outcomes:
measure: change in the concentration of short chain fatty acids in feces
timeFrame: Change from baseline concentration at four weeks
Other outcomes:
measure: Change in Body weight
timeFrame: Change from baseline weight at four weeks
measure: length
timeFrame: Baseline
measure: Change of Dietary fiber intake
timeFrame: Change from baseline dietary fiber intake at four weeks
measure: Change of dietary Liquids
timeFrame: Change from baseline liquids at four weeks
Locations:
city: Guadalajara
country: Mexico
facility: Nuevo Hospital Civil de Guadalajara
state: Jalisco
Study officials:
affiliation: full time staff member at the Division of Pediatrics of the New Civil Hospital of Guadalajara
name: Edgar M Vásquez-Garibay, Doctor
role: PRINCIPAL_INVESTIGATOR
References:
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