Synbiotic, Prebiotics and Probiotics in Children With Cerebral Palsy and Constipation
Condition: Cerebral Palsy; Chronic Constipation
MeSH terms: Paralysis; Cerebral Palsy; Constipation
Study type: Interventional
Phase: Phase 4

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).
    

Intervention name(s): agave inulin; Lactobacillus reuteri DSM 17938; maltodextrin; Oil mix (medium chain triglycerides and sunflower oil)
Intervention type(s): Biological; Biological; Other; Other
Intervention description(s): Duration: four weeks Dosage: powder 4 g/d; Duration: four weeks Dosage: 5 drops/d; Duration: four weeks Dosage: powder 4 g/d; Duration: four weeks Dosage: 5 drops/d
Allocation: Randomized
Intervention model: Factorial Assignment
Intervention model description: Three interventions in parallel against a control group
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: cerebral palsy; children; chronic constipation; synbiotic; prebiotics; probiotics; agave inulin; microbiota