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

• Sponsor: BioGaia AB (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02004288
• Collaborator: (none)
• Enrollment: 31
• Location: 1
• Arms: 2
• Duration (Months): 33
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Anorexia Nervosa; Constipation	Dietary Supplement: Lactobacillus reuteri Protectis DSM17938	N/A

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 31 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Supportive Care
• Official Title: 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
• Study Start Date: Dec 1, 2013
• Actual Primary Completion Date: Sep 1, 2016
• Actual Study Completion Date: Sep 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lactobacillus reuteri Protectis DSM17938 One chewable tablet twice per day with L reuteri Protectis DSM 17938, 1x108 CFU/tablet (colony forming unit)	Dietary Supplement: Lactobacillus reuteri Protectis DSM17938; 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.
Placebo Comparator: Placebo One chewable tablet twice per day with placebo per day	Dietary Supplement: Lactobacillus reuteri Protectis DSM17938; 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.

Outcome Measures

Primary Outcome Measures

1. Number of Participants That Drop Out From Rome III Criteria for Constipation [3 month]

   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.

Secondary Outcome Measures

1. Normalization of Body Weight [6 month]

   normalization of body weight- 90% of premorbid weight, or ≥10. centile for BMI (according to the WHO growth charts)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 8 Years to 18 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pediatric Department Clinical Hospital Centre Sestre milosrdnice Gastroenterology, Hepatology and Nutrition Ward	Zagreb		Croatia

Sponsors and Collaborators

• BioGaia AB

Investigators

• Principal Investigator: Orjena Zaja Franulovic, MD, PhD, Center for Eating disorders Sestre milosrdnice University hospital Zagreb, Croatia

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: BioGaia AB
• ClinicalTrials.gov Identifier: NCT02004288
• Other Study ID Numbers: CSUB0083
• First Posted: Dec 9, 2013
• Last Update Posted: Jun 23, 2021
• Last Verified: May 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by BioGaia AB: Probiotics; Anorexia nervosa; Constipation; Body weight
• Additional relevant MeSH terms: Constipation; Anorexia; Anorexia Nervosa

Study Results

Participant Flow

Arm/Group Title	Lactobacillus Reuteri Protectis DSM17938	Placebo
Arm/Group Description	One chewable tablet twice per day with L reuteri Protectis DSM 17938, 1x108 CFU/tablet (colony forming unit) Lactobacillus reuteri Protectis DSM17938: 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.	One chewable tablet twice per day with placebo per day Lactobacillus reuteri Protectis DSM17938: 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.
Period Title: Overall Study
STARTED	15	16
COMPLETED	14	15
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	Lactobacillus Reuteri Protectis DSM17938	Placebo	Total
Arm/Group Description	One chewable tablet twice per day with L reuteri Protectis DSM 17938, 1x108 CFU/tablet (colony forming unit) Lactobacillus reuteri Protectis DSM17938: 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.	One chewable tablet twice per day with placebo per day Lactobacillus reuteri Protectis DSM17938: 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.	Total of all reporting groups
Overall Participants	15	16	31
Age (Count of Participants)
<=18 years	15 100%	16 100%	31 100%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	15.06 (2.31)	15.13 (1.70)	15.06 (1.96)
Sex: Female, Male (Count of Participants)
Female	15 100%	16 100%	31 100%
Male	0 0%	0 0%	0 0%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
Croatia	15 100%	16 100%	31 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants That Drop Out From Rome III Criteria for Constipation
Description	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.
Time Frame	3 month

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lactobacillus Reuteri Protectis DSM17938	Placebo
Arm/Group Description	One chewable tablet twice per day with L reuteri Protectis DSM 17938, 1x108 CFU/tablet (colony forming unit) Lactobacillus reuteri Protectis DSM17938: 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.	One chewable tablet twice per day with placebo per day Lactobacillus reuteri Protectis DSM17938: 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.
Measure Participants	15	16
Count of Participants [Participants]	13 86.7%	10 62.5%

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lactobacillus Reuteri Protectis DSM17938	Placebo
Arm/Group Description	One chewable tablet twice per day with L reuteri Protectis DSM 17938, 1x108 CFU/tablet (colony forming unit) Lactobacillus reuteri Protectis DSM17938: 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.	One chewable tablet twice per day with placebo per day Lactobacillus reuteri Protectis DSM17938: 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.
Measure Participants	15	16
Count of Participants [Participants]	14 93.3%	10 62.5%

Adverse Events

Time Frame	During the study, 6 months / participant,
Arm/Group Title	Lactobacillus Reuteri Protectis DSM17938		Placebo
Arm/Group Description	One chewable tablet twice per day with L reuteri Protectis DSM 17938, 1x108 CFU/tablet (colony forming unit) Lactobacillus reuteri Protectis DSM17938: 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.		One chewable tablet twice per day with placebo per day Lactobacillus reuteri Protectis DSM17938: 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.
All Cause Mortality
	Lactobacillus Reuteri Protectis DSM17938		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/16 (0%)
Serious Adverse Events
	Lactobacillus Reuteri Protectis DSM17938		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/16 (0%)
Other (Not Including Serious) Adverse Events
	Lactobacillus Reuteri Protectis DSM17938		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/16 (0%)

Limitations/Caveats

The limitation of this study is the small number of patients. This is due to strict inclusion and exclusion criteria, as well as the fact that some parents and patients refused to participate in the survey, which is not unusual given the negativism that characterizes this disease.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.