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The goal of this clinical trial is to test the effectiveness of trimebutine and probiotics in treating Functional Abdominal Pain Disorders (FAPD) in a pediatric population. The main questions it aims to answer are: Is trimebutine effective in reducing the symptoms of FAPD in children? Are probiotics effective in reducing the symptoms of FAPD in children? Participants will be randomly assigned to one of three treatment groups (trimebutine/probiotics, probiotics/placebo, or trimebutine/placebo). Undergo measurements for pain and other relevant metrics at the start of the study, after 4 weeks, and after 8 weeks.
Researchers will compare the trimebutine/probiotics group to the probiotics/placebo and the trimebutine/placebo groups to see if there are significant differences in the efficacy of these treatments in reducing symptoms of FAPD in children.
The protocol will be submitted for review by the Research Committee and the Ethics Committee of the Regional University Hospital of Colima. Upon receiving approval, a double-blind, placebo-controlled, randomized clinical trial will be carried out, based on CONSORT guidelines. This trial involves the participation of pediatric patients aged 4 to 18.
Patients will be selected from those attending private practice and satisfying Rome IV criteria for any of the Functional Abdominal Pain Disorders (FAPD). Before any intervention takes place, the purpose and procedures of the study will be explained to both the patients and their legal guardians. If they decide to participate, they will be asked to sign an informed consent letter and assent form for minors. Patients will be selected through stratified probabilistic sampling in 4 categories (Irritable Bowel Syndrome, Functional Dyspepsia, Abdominal Migraine, and Functional Abdominal Pain not otherwise specified (FAP-NOS)) until the desired sample size of 82 participants is reached. Once participants are selected, they will be randomly assigned to one of the three groups: trimebutine/probiotic, probiotic/placebo, or trimebutine/placebo, with each group consisting of at least 20 participants. The initial diagnosis will be carried out using the Rome IV Criteria Questionnaires for pediatric patients, and the intensity of pain will be evaluated using the Visual Analog Scale (VAS) and quality of life with PedsQL 4.0. Patients will be administered the treatment corresponding to their assigned group and will be clinically followed up at 4 and 8 weeks. During these follow-up consultations, the Rome IV Criteria Questionnaires and scales will be reapplied to assess the evolution of the patients' symptoms and their response to treatment. Any patient who requests voluntary withdrawal, those with treatment adherence less than 80%, and those participating in another study or being treated by another physician simultaneously will be removed from the study.
Statistical analysis will be carried out using international Business Machine (IBM®) Statistical Package for the Social Sciences (SPSS®) Statistics 26. Descriptive statistics with measures of central tendency will be used, presenting the results in tables and graphs. To determine whether the data follow a normal distribution, the Kolmogorov-Smirnov and Shapiro-Wilk tests will be applied. Measurements in 3 groups (trimebutine, probiotics, and control) and at 3 times (0, 4, and 8 weeks) will be analyzed. For intervening categorical variables like gender and education, the chi-square test (X2) will be used. For continuous variables like age and BMI, the Mann-Whitney U test will be applied, expecting statistically significant differences with p < 0.05.
If the data follow a normal distribution, repeated measures ANOVA will be used to compare the means of the 3 groups (trimebutine, probiotics, and placebo). McNemar's test or the sign test will be considered as secondary analyses to evaluate changes within each group over time (0, 4, and 8 weeks). If the data do not follow a normal distribution, non-parametric tests like the Friedman test will be employed.
In case of finding a statistically significant difference in repeated measures ANOVA or the Friedman test, post hoc tests will be performed to identify specific differences between groups and times. If necessary, correlation tests like Pearson or Spearman will be used to evaluate relationships between different variables within the study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Trimebutine + Probiotic | Experimental | Participants received trimebutine in 200 mg tablets or 20 mg/ml suspension at a dose of 15 mg/kg/day adjusted to their weight, divided into 2 doses (morning and night) + Lactobacillus rhamnosus 5 billion Colony Forming Units (CFUs) in chewable tablets, a single dose (night), for a period of 8 weeks. |
|
| Trimebutine + Placebo | Active Comparator | Participants received trimebutine in 200 mg tablets or 20 mg/ml suspension at a dose of 15 mg/kg/day adjusted to their weight, divided into 2 doses (morning and night) + Placebo, 250 mg microcrystalline cellulose tablets, a single dose (night), for a period of 8 weeks. |
|
| Probiotic + Placebo | Active Comparator | Participants received Lactobacillus rhamnosus 5 billion Colony Forming Units (CFUs) in chewable tablets + Placebo, 250 mg microcrystalline cellulose tablets, a single dose (night), for a period of 8 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Trimebutine | Drug | Prescription of trimebutine at pediatric dosage (15 mg/kg/day), divided into 2 daily doses, for 8 weeks. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Average Score on Visual Analog Scale for Abdominal Pain | Participants rated the highest intensity of abdominal pain they experienced during the past eight weeks on a scale of 0 (no pain) to 10 (worst pain imaginable), using an Visual Analog Scale (VAS) scale. A decrease in the score signifies an improvement in symptoms. | Baseline to 8 weeks post-treatment. |
| Measure | Description | Time Frame |
|---|---|---|
| Improvement in Quality of Life with PedsQL 3.0 | Impact of the treatment on the Quality of Life in pediatric patients with FAPD. The PedsQL 0 - 100 scoring system is used, where higher scores indicate better quality of life. The change in scores from baseline to 8 weeks post-treatment is measured. | Baseline to 8 weeks post-treatment. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants with Treatment-Related Adverse Events | Number and type of treatment-related adverse events reported during the study period, evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. | Baseline to 8 weeks post-treatment. |
Inclusion Criteria:
Exclusion Criteria:
Elimination Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Pablo H Sandoval-Villaseñor, MD | Contact | +523123007655 | pablohernan_sandoval@ucol.mx | |
| Fabián Rojas-Larios, PhD | Contact | +523121206804 | frojas@ucol.mx |
| Name | Affiliation | Role |
|---|---|---|
| Pablo H Sandoval-Villaseñor, MD | Universidad de Colima | Principal Investigator |
| Fabián Rojas-Larios, PhD | Universidad de Colima | Study Director |
| Carmen A Sánchez-RamÃrez, PhD |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| School of Medicine, University of Colima | Recruiting | Colima | 28040 | Mexico |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25992621 | Background | Korterink JJ, Diederen K, Benninga MA, Tabbers MM. Epidemiology of pediatric functional abdominal pain disorders: a meta-analysis. PLoS One. 2015 May 20;10(5):e0126982. doi: 10.1371/journal.pone.0126982. eCollection 2015. | |
| 31022401 | Background | Simren M, Tornblom H, Palsson OS, Van Oudenhove L, Whitehead WE, Tack J. Cumulative Effects of Psychologic Distress, Visceral Hypersensitivity, and Abnormal Transit on Patient-reported Outcomes in Irritable Bowel Syndrome. Gastroenterology. 2019 Aug;157(2):391-402.e2. doi: 10.1053/j.gastro.2019.04.019. Epub 2019 Apr 22. |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP_ICF | Yes | Yes | Yes | Study Protocol, Statistical Analysis Plan, and Informed Consent Form | Jan 9, 2024 |
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| Lactobacillus rhamnosus | Dietary Supplement | Prescription of Lactobacillus rhamnosus 5 billion CFUs in chewable tablets, a single dose (night) for 8 weeks. |
|
| Placebo | Other | Prescription of a placebo, 250 mg microcrystalline cellulose tablets, a single dose (night) for 8 weeks. |
|
|
| Improvement in Quality of Life with PedsQL 3.0 |
Impact of the treatment on the Quality of Life in pediatric patients with FAPD. The PedsQL 0 - 100 scoring system is used, where higher scores indicate better quality of life. The change in scores from baseline to 4 weeks post-treatment is measured. |
| Baseline to 4 weeks post-treatment. |
| Average Score on Visual Analog Scale for Abdominal Pain | Participants rated the highest intensity of abdominal pain they experienced during the past eight weeks on a scale of 0 (no pain) to 10 (worst pain imaginable), using an Visual Analog Scale (VAS) scale. A decrease in the score signifies an improvement in symptoms. | Baseline to 4 weeks post-treatment. |
| Universidad de Colima |
| Study Director |
| 33154368 | Background | Thapar N, Benninga MA, Crowell MD, Di Lorenzo C, Mack I, Nurko S, Saps M, Shulman RJ, Szajewska H, van Tilburg MAL, Enck P. Paediatric functional abdominal pain disorders. Nat Rev Dis Primers. 2020 Nov 5;6(1):89. doi: 10.1038/s41572-020-00222-5. |
| 31528110 | Background | Ding FCL, Karkhaneh M, Zorzela L, Jou H, Vohra S. Probiotics for paediatric functional abdominal pain disorders: A rapid review. Paediatr Child Health. 2019 Sep;24(6):383-394. doi: 10.1093/pch/pxz036. Epub 2019 May 4. |
| 22889919 | Background | Horvath A, Dziechciarz P, Szajewska H. Systematic review of randomized controlled trials: fiber supplements for abdominal pain-related functional gastrointestinal disorders in childhood. Ann Nutr Metab. 2012;61(2):95-101. doi: 10.1159/000338965. |
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| 23350053 | Background | Karabulut GS, Beser OF, Erginoz E, Kutlu T, Cokugras FC, Erkan T. The Incidence of Irritable Bowel Syndrome in Children Using the Rome III Criteria and the Effect of Trimebutine Treatment. J Neurogastroenterol Motil. 2013 Jan;19(1):90-3. doi: 10.5056/jnm.2013.19.1.90. Epub 2013 Jan 8. |
| 36799531 | Background | Wallace C, Gordon M, Sinopoulou V, Akobeng AK. Probiotics for management of functional abdominal pain disorders in children. Cochrane Database Syst Rev. 2023 Feb 17;2(2):CD012849. doi: 10.1002/14651858.CD012849.pub2. |
| 27144632 | Background | Hyams JS, Di Lorenzo C, Saps M, Shulman RJ, Staiano A, van Tilburg M. Functional Disorders: Children and Adolescents. Gastroenterology. 2016 Feb 15:S0016-5085(16)00181-5. doi: 10.1053/j.gastro.2016.02.015. Online ahead of print. |
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| 29747935 | Background | Saps M, Velasco-Benitez CA, Langshaw AH, Ramirez-Hernandez CR. Prevalence of Functional Gastrointestinal Disorders in Children and Adolescents: Comparison Between Rome III and Rome IV Criteria. J Pediatr. 2018 Aug;199:212-216. doi: 10.1016/j.jpeds.2018.03.037. Epub 2018 May 7. |
| 28092724 | Background | Koppen IJ, Nurko S, Saps M, Di Lorenzo C, Benninga MA. The pediatric Rome IV criteria: what's new? Expert Rev Gastroenterol Hepatol. 2017 Mar;11(3):193-201. doi: 10.1080/17474124.2017.1282820. Epub 2017 Jan 24. |
| 20528117 | Background | Chiou E, Nurko S. Management of functional abdominal pain and irritable bowel syndrome in children and adolescents. Expert Rev Gastroenterol Hepatol. 2010 Jun;4(3):293-304. doi: 10.1586/egh.10.28. |
| 29380480 | Background | Koppen IJN, Saps M, Lavigne JV, Nurko S, Taminiau JAJM, Di Lorenzo C, Benninga MA. Recommendations for pharmacological clinical trials in children with functional constipation: The Rome foundation pediatric subcommittee on clinical trials. Neurogastroenterol Motil. 2018 Apr;30(4):e13294. doi: 10.1111/nmo.13294. Epub 2018 Jan 30. |
| 27144631 | Background | Benninga MA, Faure C, Hyman PE, St James Roberts I, Schechter NL, Nurko S. Childhood Functional Gastrointestinal Disorders: Neonate/Toddler. Gastroenterology. 2016 Feb 15:S0016-5085(16)00182-7. doi: 10.1053/j.gastro.2016.02.016. Online ahead of print. |
| 29881232 | Background | Devanarayana NM, Rajindrajith S. Irritable bowel syndrome in children: Current knowledge, challenges and opportunities. World J Gastroenterol. 2018 Jun 7;24(21):2211-2235. doi: 10.3748/wjg.v24.i21.2211. |
| 25557967 | Background | van Tilburg MA, Hyman PE, Walker L, Rouster A, Palsson OS, Kim SM, Whitehead WE. Prevalence of functional gastrointestinal disorders in infants and toddlers. J Pediatr. 2015 Mar;166(3):684-9. doi: 10.1016/j.jpeds.2014.11.039. Epub 2014 Dec 31. |
| 27316779 | Background | Chumpitazi BP, Weidler EM, Lu DY, Tsai CM, Shulman RJ. Self-Perceived Food Intolerances Are Common and Associated with Clinical Severity in Childhood Irritable Bowel Syndrome. J Acad Nutr Diet. 2016 Sep;116(9):1458-1464. doi: 10.1016/j.jand.2016.04.017. Epub 2016 Jun 15. |
| 27144624 | Background | Van Oudenhove L, Crowell MD, Drossman DA, Halpert AD, Keefer L, Lackner JM, Murphy TB, Naliboff BD, Levy RL. Biopsychosocial Aspects of Functional Gastrointestinal Disorders. Gastroenterology. 2016 Feb 18:S0016-5085(16)00218-3. doi: 10.1053/j.gastro.2016.02.027. Online ahead of print. |
| 24076059 | Background | Halmos EP, Power VA, Shepherd SJ, Gibson PR, Muir JG. A diet low in FODMAPs reduces symptoms of irritable bowel syndrome. Gastroenterology. 2014 Jan;146(1):67-75.e5. doi: 10.1053/j.gastro.2013.09.046. Epub 2013 Sep 25. |
| 28334433 | Background | Newlove-Delgado TV, Martin AE, Abbott RA, Bethel A, Thompson-Coon J, Whear R, Logan S. Dietary interventions for recurrent abdominal pain in childhood. Cochrane Database Syst Rev. 2017 Mar 23;3(3):CD010972. doi: 10.1002/14651858.CD010972.pub2. |
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| 23220208 | Background | Rutten JM, Reitsma JB, Vlieger AM, Benninga MA. Gut-directed hypnotherapy for functional abdominal pain or irritable bowel syndrome in children: a systematic review. Arch Dis Child. 2013 Apr;98(4):252-7. doi: 10.1136/archdischild-2012-302906. Epub 2012 Dec 6. |
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| 32650518 | Background | Kountouras J, Gavalas E, Papaefthymiou A, Tsechelidis I, Polyzos SA, Bor S, Diculescu M, Jadallah Kappa, Tadeusz M, Karakan T, Bochenek Alpha, Rozciecha J, Dabrowski P, Sparchez Z, Sezgin O, Gulten M, Farsakh NA, Doulberis M. Trimebutine Maleate Monotherapy for Functional Dyspepsia: A Multicenter, Randomized, Double-Blind Placebo Controlled Prospective Trial. Medicina (Kaunas). 2020 Jul 8;56(7):339. doi: 10.3390/medicina56070339. |
| 31110953 | Background | Vandenplas Y, Hauser B, Salvatore S. Functional Gastrointestinal Disorders in Infancy: Impact on the Health of the Infant and Family. Pediatr Gastroenterol Hepatol Nutr. 2019 May;22(3):207-216. doi: 10.5223/pghn.2019.22.3.207. Epub 2019 Apr 16. |
| 33948025 | Background | Salminen S, Collado MC, Endo A, Hill C, Lebeer S, Quigley EMM, Sanders ME, Shamir R, Swann JR, Szajewska H, Vinderola G. The International Scientific Association of Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of postbiotics. Nat Rev Gastroenterol Hepatol. 2021 Sep;18(9):649-667. doi: 10.1038/s41575-021-00440-6. Epub 2021 May 4. |
| 30154898 | Background | Dryl R, Szajewska H. Probiotics for management of infantile colic: a systematic review of randomized controlled trials. Arch Med Sci. 2018 Aug;14(5):1137-1143. doi: 10.5114/aoms.2017.66055. Epub 2017 Feb 16. |
| 21078735 | Background | Francavilla R, Miniello V, Magista AM, De Canio A, Bucci N, Gagliardi F, Lionetti E, Castellaneta S, Polimeno L, Peccarisi L, Indrio F, Cavallo L. A randomized controlled trial of Lactobacillus GG in children with functional abdominal pain. Pediatrics. 2010 Dec;126(6):e1445-52. doi: 10.1542/peds.2010-0467. Epub 2010 Nov 15. |
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| 22036893 | Background | Moher D, Hopewell S, Schulz KF, Montori V, Gotzsche PC, Devereaux PJ, Elbourne D, Egger M, Altman DG; CONSORT. CONSORT 2010 explanation and elaboration: updated guidelines for reporting parallel group randomised trials. Int J Surg. 2012;10(1):28-55. doi: 10.1016/j.ijsu.2011.10.001. Epub 2011 Oct 12. |
| Feb 16, 2024 |
| Prot_SAP_ICF_000.pdf |
| ID | Term |
|---|---|
| D005767 | Gastrointestinal Diseases |
| ID | Term |
|---|---|
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| D014287 | Trimebutine |
| C109691 | microcrystalline cellulose |
| ID | Term |
|---|---|
| D062425 | Hydroxybenzoate Ethers |
| D062385 | Hydroxybenzoates |
| D001565 | Benzoates |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
| D006880 | Hydroxy Acids |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D010647 | Phenyl Ethers |
| D010636 | Phenols |
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