The Effect of Probiotics on Constipation, and Intestinal Microflora in Children With Functional Constipation

• Sponsor: Chang Gung Memorial Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT03054805
• Collaborator: (none)
• Enrollment: 153
• Arms: 3
• Duration (Months): 21

Study Details

Study Description

Brief Summary

To compare the differences of fecal microflora between constipated and non-constipated healthy children, and evaluate the efficacy of probiotics in reducing symptoms of constipation and the influence of intestinal microflora in children with functional constipation.

Condition or Disease	Intervention/Treatment	Phase
Functional Constipation	Drug: Magnesium Oxide; Drug: MIYAIRI-BM	Phase 4

Detailed Description

The investigators performed a monocentric, prospective, randomized controlled trial including 120 pediatric patients (aged 6 months - 10 years old) with functional constipation and 30 healthy age-matched healthy children as control. The investigators shall evaluate the children according to the Rome III Diagnostic Criteria for functional constipation.

The 120 enrolled patients are randomized in to two groups: Group A receiving magnesium oxide and probiotics (MIYAIRI-BM), Group B receiving only magnesium oxide. Each patient is assigned the evaluation constipation symptoms and detection of microflora (beneficial and harmful bacteria) in fecal samples at the enrollment, 4 weeks, and 12 weeks. Patients who take less than 80% of the appropriate dose of medications are withdrawn from the study. All patients included in the study will be given informed oral consent before entering the study.

The data of the fecal microflora evaluated in 60 healthy children are used as control.

Study Design

• Study Type: Interventional
• Actual Enrollment: 153 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: The Effect of Probiotics on Constipation, and Intestinal Microflora in Children With Functional Constipation
• Study Start Date: Sep 1, 2014
• Actual Primary Completion Date: Dec 1, 2014
• Actual Study Completion Date: Jun 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Magnesium oxide and MIYAIRI-BM Magnesium oxide 125 mg twice per day for children with weight < 15 kg, 250 mg twice per day for weight <15-30 kg, and 500 mg twice per day for weight > 30 kg for 12 weeks. MIYAIRI-BM 1 package (1g) divided as 0.5 g twice per day for children with weight < 15 kg, 2 packages divided as 1 g twice per day for weight 15-30 kg, and 3 packages divided as 1.5 g twice per day for weight > 30 kg for 12 weeks.	Drug: Magnesium Oxide; Magnesium oxide 250 mg per day for children with weight < 15 kg, 500 mg per day for weight <15-30 kg, and 1000 mg per day for weight > 30 kg; Other Names: MgO ; Drug: MIYAIRI-BM; MIYAIRI-BM 1 g (1package) per day for children with weight < 15 kg, 2g per day for weight 15-30 kg, and 3g per day for weight > 30 kg; Other Names: Clostridium Butyricum MIYAIRI
Active Comparator: Magnesium oxide MIYAIRI-BM 1 package (1g) divided as 0.5 g twice per day for children with weight < 15 kg, 2 packages divided as 1 g twice per day for weight 15-30 kg, and 3 packages divided as 1.5 g twice per day for weight > 30 kg for 12 weeks.	Drug: Magnesium Oxide; Magnesium oxide 250 mg per day for children with weight < 15 kg, 500 mg per day for weight <15-30 kg, and 1000 mg per day for weight > 30 kg; Other Names: MgO
No Intervention: Healthy Children Healthy Children

Outcome Measures

Primary Outcome Measures

1. Change of Clostridium Butyricum Miyairi Expression After Probiotics Supplementation in Constipated Children. [Change from baseline Clostridium butyricum Miyairi expression at 3 months.]

   The expression of Clostridium butyricum Miyairi (CBM) in constipated children feces means a better outcome measure.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Months to 10 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

Rome III Diagnostic Criteria for functional constipation for children aged 6 months - 4 years old is as the following:

1. Two or fewer defecations per week.

2. At least one episode per week of incontinence after acquiring toileting skills.

3. History of excessive stool retention.

4. History of painful or hard bowel movements.

5. Presence of a large fecal mass in the rectum.

6. History of large-diameter stools that may obstruct the toilet. Children aged 6 months

• 4 years old is evaluated as functional constipation if two of the situations mentioned above lasted for one month.

Rome III Diagnostic Criteria for functional constipation for children aged 4 years old and above is as the following:

1. Two or fewer defecations in the toilet per week.

2. At least one episode of fecal incontinence per week.

3. History of retentive posturing or excessive volitional stool retention.

4. History of painful or hard bowel movements.

5. Presence of a large fecal mass in the rectum.

6. History of large diameter stools that may obstruct the toilet. Children aged 4 years old and above is evaluated as functional constipation if two of the situations mentioned above happens at least once per week

Exclusion Criteria:

1. gastroesophageal reflux disease

2. inflammatory bowel disease

3. cardiopulmonary diseases

4. liver disease

5. renal disease

6. genetic diseases

7. endocrinal diseases

8. received abdominal surgeries

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Chang Gung Memorial Hospital

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Chang Gung Memorial Hospital
• ClinicalTrials.gov Identifier: NCT03054805
• Other Study ID Numbers: 103-0519A3
• First Posted: Feb 16, 2017
• Last Update Posted: Aug 14, 2019
• Last Verified: Sep 1, 2014

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Constipation; Magnesium Oxide

Study Results

Participant Flow

Recruitment Details	This trial is expected to recruit 180 children, but the actual willingness to participate in the trial is 153 children.

Arm/Group Title	Magnesium Oxide and MIYAIRI-BM	Magnesium Oxide	Healthy Children
Arm/Group Description	Magnesium oxide 125 mg twice per day for children with weight < 15 kg, 250 mg twice per day for weight <15-30 kg, and 500 mg twice per day for weight > 30 kg for 12 weeks. MIYAIRI-BM 1 package (1g) divided as 0.5 g twice per day for children with weight < 15 kg, 2 packages divided as 1 g twice per day for weight 15-30 kg, and 3 packages divided as 1.5 g twice per day for weight > 30 kg for 12 weeks. Magnesium Oxide: Magnesium oxide 250 mg per day for children with weight < 15 kg, 500 mg per day for weight <15-30 kg, and 1000 mg per day for weight > 30 kg MIYAIRI-BM: MIYAIRI-BM 1 g (1package) per day for children with weight < 15 kg, 2g per day for weight 15-30 kg, and 3g per day for weight > 30 kg	MIYAIRI-BM 1 package (1g) divided as 0.5 g twice per day for children with weight < 15 kg, 2 packages divided as 1 g twice per day for weight 15-30 kg, and 3 packages divided as 1.5 g twice per day for weight > 30 kg for 12 weeks. Magnesium Oxide: Magnesium oxide 250 mg per day for children with weight < 15 kg, 500 mg per day for weight <15-30 kg, and 1000 mg per day for weight > 30 kg	Healthy children without any treatment
Period Title: Overall Study
STARTED	58	51	44
COMPLETED	42	41	42
NOT COMPLETED	16	10	2

Baseline Characteristics

Arm/Group Title	Magnesium Oxide and MIYAIRI-BM	Magnesium Oxide	Healthy Children	Total
Arm/Group Description	Magnesium oxide 125 mg twice per day for children with weight < 15 kg, 250 mg twice per day for weight <15-30 kg, and 500 mg twice per day for weight > 30 kg for 12 weeks. MIYAIRI-BM 1 package (1g) divided as 0.5 g twice per day for children with weight < 15 kg, 2 packages divided as 1 g twice per day for weight 15-30 kg, and 3 packages divided as 1.5 g twice per day for weight > 30 kg for 12 weeks. Magnesium Oxide: Magnesium oxide 250 mg per day for children with weight < 15 kg, 500 mg per day for weight <15-30 kg, and 1000 mg per day for weight > 30 kg MIYAIRI-BM: MIYAIRI-BM 1 g (1package) per day for children with weight < 15 kg, 2g per day for weight 15-30 kg, and 3g per day for weight > 30 kg	MIYAIRI-BM 1 package (1g) divided as 0.5 g twice per day for children with weight < 15 kg, 2 packages divided as 1 g twice per day for weight 15-30 kg, and 3 packages divided as 1.5 g twice per day for weight > 30 kg for 12 weeks. Magnesium Oxide: Magnesium oxide 250 mg per day for children with weight < 15 kg, 500 mg per day for weight <15-30 kg, and 1000 mg per day for weight > 30 kg	Healthy children without any treatment	Total of all reporting groups
Overall Participants	42	41	42	125
Age (Count of Participants)
<=18 years	42 100%	41 100%	42 100%	125 100%
Between 18 and 65 years	0 0%	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	2.75 (1.25)	3.92 (1.83)	4.08 (2.41)	3.58 (1.83)
Sex: Female, Male (Count of Participants)
Female	24 57.1%	23 56.1%	17 40.5%	64 51.2%
Male	18 42.9%	18 43.9%	25 59.5%	61 48.8%

Outcome Measures

1. Primary Outcome

Title	Change of Clostridium Butyricum Miyairi Expression After Probiotics Supplementation in Constipated Children.
Description	The expression of Clostridium butyricum Miyairi (CBM) in constipated children feces means a better outcome measure.
Time Frame	Change from baseline Clostridium butyricum Miyairi expression at 3 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Magnesium Oxide and MIYAIRI-BM	Magnesium Oxide	Healthy Children
Arm/Group Description	Magnesium oxide 125 mg twice per day for children with weight < 15 kg, 250 mg twice per day for weight <15-30 kg, and 500 mg twice per day for weight > 30 kg for 12 weeks. MIYAIRI-BM 1 package (1g) divided as 0.5 g twice per day for children with weight < 15 kg, 2 packages divided as 1 g twice per day for weight 15-30 kg, and 3 packages divided as 1.5 g twice per day for weight > 30 kg for 12 weeks. Magnesium Oxide: Magnesium oxide 250 mg per day for children with weight < 15 kg, 500 mg per day for weight <15-30 kg, and 1000 mg per day for weight > 30 kg MIYAIRI-BM: MIYAIRI-BM 1 g (1package) per day for children with weight < 15 kg, 2g per day for weight 15-30 kg, and 3g per day for weight > 30 kg	MIYAIRI-BM 1 package (1g) divided as 0.5 g twice per day for children with weight < 15 kg, 2 packages divided as 1 g twice per day for weight 15-30 kg, and 3 packages divided as 1.5 g twice per day for weight > 30 kg for 12 weeks. Magnesium Oxide: Magnesium oxide 250 mg per day for children with weight < 15 kg, 500 mg per day for weight <15-30 kg, and 1000 mg per day for weight > 30 kg	Healthy children without any treatment
Measure Participants	42	41	42
Mean (Standard Deviation) [number of bacteria per mg of feces]	0.00486 (0.00696)	0.0000148 (0.0000266)	0.00000189 (0.00000341)

Adverse Events

Time Frame	3 months
Arm/Group Title	Magnesium Oxide and MIYAIRI-BM		Magnesium Oxide		Healthy Children
Arm/Group Description	Magnesium oxide 125 mg twice per day for children with weight < 15 kg, 250 mg twice per day for weight <15-30 kg, and 500 mg twice per day for weight > 30 kg for 12 weeks. MIYAIRI-BM 1 package (1g) divided as 0.5 g twice per day for children with weight < 15 kg, 2 packages divided as 1 g twice per day for weight 15-30 kg, and 3 packages divided as 1.5 g twice per day for weight > 30 kg for 12 weeks. Magnesium Oxide: Magnesium oxide 250 mg per day for children with weight < 15 kg, 500 mg per day for weight <15-30 kg, and 1000 mg per day for weight > 30 kg MIYAIRI-BM: MIYAIRI-BM 1 g (1package) per day for children with weight < 15 kg, 2g per day for weight 15-30 kg, and 3g per day for weight > 30 kg		MIYAIRI-BM 1 package (1g) divided as 0.5 g twice per day for children with weight < 15 kg, 2 packages divided as 1 g twice per day for weight 15-30 kg, and 3 packages divided as 1.5 g twice per day for weight > 30 kg for 12 weeks. Magnesium Oxide: Magnesium oxide 250 mg per day for children with weight < 15 kg, 500 mg per day for weight <15-30 kg, and 1000 mg per day for weight > 30 kg		Healthy children without any treatment
All Cause Mortality
	Magnesium Oxide and MIYAIRI-BM		Magnesium Oxide		Healthy Children
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/58 (0%)		0/51 (0%)		0/44 (0%)
Serious Adverse Events
	Magnesium Oxide and MIYAIRI-BM		Magnesium Oxide		Healthy Children
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/58 (0%)		0/51 (0%)		0/44 (0%)
Other (Not Including Serious) Adverse Events
	Magnesium Oxide and MIYAIRI-BM		Magnesium Oxide		Healthy Children
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/58 (0%)		0/51 (0%)		0/44 (0%)

Limitations/Caveats

[Not Specified]

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.