The Role of Lactobacillus Reuteri in Children and Adolescents With Anorexia Nervosa

Study Overview
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Brief Summary
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The aim of this study is to investigate whether Lactobacillus reuteri could have a beneficial role in treatment of children and adolescents with Anorexia nervosa who develop motility disorder due to the malnutrition regarding the normalization of the motility, as well as the possible role of probiotics on nutritional recovery, especially on bone health.

Detailed Description
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Pediatric patients with AN and constipation referred to gastroenterologist for nutritional rehabilitation at the Department of Pediatric Gastroenterology, Hepatology and Nutrition, Clinical Hospital Center Sestre Milosrdnice, Zagreb, approximately 30 children, will be asked to participate. The evaluation of patients will be conducted through APA DSM-V diagnostic criteria for anorexia nervosa and Rome III criteria for constipation. During the hospitalization all of the patients will receive conventional nutritional rehabilitation that is composed of serving normal food under supervision of nurses that calculate daily caloric intake through 5-6 meals and according to that additional enteral nutrition that consist of polymeric enteral formula. Daily caloric intake is calculated as kcal/kg/day and is slowly rising through 2 weeks starting from 80% to the goal of 130% of daily energy requirements according to FAO 2004 recommendation. Anthropometry measures will be taken at the time of hospitalization and at every visit. Normalization of weight is when the Z-score for BMI is less than -1.5 according to CDC BMI-growth charts, or normalisation of menstrual cycle is achieved. In order to achieve adherence to therapeutic protocol parents will be contacted by phone at least once in 7-10 days. Participants will be instructed to keep diary on a daily basis (adherence to therapy, stool diary). All patients will return packages with all used, and unused product. BASELINE -VISIT 1 Randomization at first day of hospitalization. In all patients anthropometry will be performed at the time of hospitalization, as well as dual-energy X-ray absorptiometry (DEXA) and serum D3 levels at first 2 days of hospitalization as a part of routine diagnostic protocol in heavily underweight patients with AN. VISIT 2 4 weeks after randomization, at discharge from hospital Anthropometry VISIT 3 8 weeks after randomization, 4 weeks after discharge from hospital Anthropometry END OF STUDY -VISIT 4 3 months after baseline Anthropometry VISIT 5 3 months after the end of study (6 months after baseline) At this point control serum D3 levels and DEXA will be performed at all patients Anthropometry All the symptoms and daily caloric intake will be monitored using diaries attached to protocol.

Official Title
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The Role of Lactobacillus Reuteri in Nutritional Recovery and Treatment of Constipation in Children and Adolescents With Anorexia Nervosa - Randomised, Double Blind, Placebo Controlled Study

Conditions
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Anorexia Nervosa, Constipation

Intervention / Treatment
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* Dietary Supplement: Lactobacillus reuteri Protectis DSM17938


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pediatric patients with Anorexia nervosa and constipation, aged 8-18 years Exclusion Criteria: AN and constipation present for less than 3 month prior to hospitalization any disease that affects GI or other systems other than AN or functional constipation chronic disorder other than AN receiving probiotic and/or prebiotic products 14 days prior to enrolment receiving antibiotics 14 days prior to enrolment constipation prior AN receiving laxative as a therapy for constipation or abuse of laxative to lose weight prior to enrolment extraintestinal symptoms: fever, rash abnormalities in laboratory findings abnormalities in clinical findings: organomegaly, perianal disease

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lactobacillus reuteri Protectis DSM17938<br>One chewable tablet twice per day with L reuteri Protectis DSM 17938, 1x108 CFU/tablet (colony forming unit) | Dietary Supplement: Lactobacillus reuteri Protectis DSM17938<br>* One chewable tablet with L. reuteri or placebo taken twice a day for 3 months. After the 3 month therapy both groups will be monitored for the next 3 months.<br>|
| Placebo Comparator: Placebo<br>One chewable tablet twice per day with placebo per day | Dietary Supplement: Lactobacillus reuteri Protectis DSM17938<br>* One chewable tablet with L. reuteri or placebo taken twice a day for 3 months. After the 3 month therapy both groups will be monitored for the next 3 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants That Drop Out From Rome III Criteria for Constipation | Drop out from Rome III criteria for constipation: Yes / No. According to Rome III, a diagnosis of functional constipation is made when at least two of the following criteria are met for the last 3 months with symptom onset at least 6 months prior to diagnosis: a) straining on >25% of defecations; b) lumpy or hard stools on >25% of defecations; c) sensation of incomplete evacuation on >25% of defecations; d) sensation of anorectal obstruction/blockage on >25% of defecations; e) manual maneuvers on >25% of defecations; and f) less than 3 defecations per week. | 3 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Normalization of Body Weight | normalization of body weight- 90% of premorbid weight, or ≥10. centile for BMI (according to the WHO growth charts) | 6 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Probiotics, Anorexia nervosa, Constipation, Body weight