Constipation
Conditions
Brief summary
The aim of this study is to assess the effectiveness of Lactobacillus casei rhamnosus Lcr35 administration for the treatment of functional constipation in children.
Detailed description
Functional constipation is a common problem which affects over 3% of children. The standard treatment does not provide sustained relief of symptoms. As a consequence, there is interest in other therapeutic options. Previously, one small (n=40) randomized controlled trial (RCT) involving 27 children showed that Lactobacillus rhamnosus casei Lcr35 compared with placebo increased treatment success defined as ≥ 3 spontaneous defecations per week with no episodes of faecal soiling, increased the defecation frequency, reduced the frequency of abdominal pain, reduced the use of glycerin enemas during the four weeks of therapy, and decreased the percentage of hard stools. However, there was no difference between groups in the use of lactulose or the number of episodes of faecal soiling. Available evidence is insufficient to draw meaningful conclusion. Further studies are needed.
Interventions
DIETARY_SUPPLEMENTLactobacillus casei rhamnosus Lcr35
Eligible children will receive Lactobacillus casei rhamnosus Lcr35 (8×10\^8 CFU, twice daily, orally for 4 weeks)
DIETARY_SUPPLEMENTPlacebo
Eligible children will receive placebo (maltodextrin), twice daily, orally for 4 weeks
Sponsors
Medical University of Warsaw
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
No minimum to 5 Years
Healthy volunteers
No
Inclusion criteria
* Children below 5 years of age * Functional constipation according to Rome III criteria i.e. 1 month of at least 2 of the following: * Two or fewer defecations per week * At least 1 episode per week of incontinence after the acquisition of toileting skills * History of excessive stool retention * History of painful or hard bowel movements * Presence of a large fecal mass in the rectum * History of large- diameter stools that may obstruct the toilet
Exclusion criteria
* Irritable bowel syndrome * Mental retardation * Endocrine disease (e.g. hypothyroidism) * Organic cause of constipation (e.g. Hirschsprung disease) * Spinal anomalies * Anatomic defects of the anorectum * History of previous gastrointestinal surgery * Functional nonretentive fecal incontinence * Use of drugs that influence gastrointestinal motility
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants With Treatment Success (≥3 Spontaneous Defecations Per Week With no Fecal Soiling | in the fourth week of the intervention |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Defecation Frequency at Week 4 | during fourth week of intervention | For single value median was calculated. |
| Fecal Soiling Episodes at Week 4 | during fourth week of intervention | For single value median was calculated. |
| Number of Defecations That Were Painful at Week 4 | during fourth weeks of intervention | Pain reported by child or symptoms of pain observed by parents. For single value median was calculated. |
| Abdominal Pain at Week 4 | during fourth weeks of intervention | Abdominal pain reported by child or symptoms of pain observed by parents. For single value median was calculated. |
| Number of Participants With Use of Laxatives | during 4 weeks of intervention | — |
| Number of Participants With Adverse Effects | during 4 weeks of intervention | — |
| Stool Consistency at Week 4 | during fourth week of intervention | Stool consistency scores were determined using the 7-point Bristol Stool Form Scale (1 for hard lumps to 7 for watery stools). For single value median was calculated. |
| Defecation Frequency at Week 1 | during first week of intervention | — |
| Fecal Soiling Episodes at Week 1 | during first week of intervention | — |
| Pain During Defecation at Week 1 | during first weeks of intervention | Pain reported by child or symptoms of pain observed by parents. For single value median was calculated. |
| Abdominal Pain at Week 1 | during first weeks of intervention | Abdominal pain reported by child or symptoms of pain observed by parents. For single value median was calculated. |
| Flatulence at Week 4 | during fourth weeks of intervention | Flatulence reported by child or symptoms of pain observed by parents. For single value median was calculated. |
| Flatulence at Week 1 | during first weeks of intervention | Flatulence reported by child or symptoms of pain observed by parents. For single value median was calculated. |
| Stool Consistency at Week 1 | during first week of intervention | Stool consistency scores were determined using the 7-point Bristol Stool Form Scale (1 for hard lumps to 7 for watery stools). For single value median was calculated. |
Countries
Poland
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lactobacillus Casei Rhamnosus Lcr35 Eligible children will receive Lactobacillus casei rhamnosus Lcr35 8×10\^8 colony forming units (CFU), twice daily, orally for 4 weeks
Lactobacillus casei rhamnosus Lcr35: Eligible children will receive Lactobacillus casei rhamnosus Lcr35 (8×10\^8 CFU, twice daily, orally for 4 weeks) | 48 |
| Placebo Eligible children will receive placebo (maltodextrin), twice daily, orally for 4 weeks
Placebo: Eligible children will receive placebo (maltodextrin), twice daily, orally for 4 weeks | 46 |
| Total | 94 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 2 |
| Overall Study | Lack of Efficacy | 1 | 0 |
| Overall Study | Lost to Follow-up | 3 | 4 |
Baseline characteristics
| Characteristic | Total | Lactobacillus Casei Rhamnosus Lcr35 | Placebo |
|---|---|---|---|
| Abdominal pain | 56 Participants | 27 Participants | 29 Participants |
| Age, Continuous | 38 month STANDARD_DEVIATION 13.1 | 38.7 month STANDARD_DEVIATION 12.1 | 37.3 month STANDARD_DEVIATION 14.2 |
| Age of onset of constipation | 23.77 months STANDARD_DEVIATION 12.45 | 24.0 months STANDARD_DEVIATION 12.1 | 23.5 months STANDARD_DEVIATION 12.9 |
| Blood in the stool | 31 Participants | 17 Participants | 14 Participants |
| Duration of constipation | 14.3 months STANDARD_DEVIATION 10.1 | 14.7 months STANDARD_DEVIATION 9.1 | 13.8 months STANDARD_DEVIATION 11.1 |
| Fecal soiling | 42 Participants | 21 Participants | 21 Participants |
| Pain during defecation | 91 Participants | 47 Participants | 44 Participants |
| Previous treatment for intestinal constipation | 77 Participants | 40 Participants | 37 Participants |
| Rectal impaction | 70 Participants | 35 Participants | 35 Participants |
| Region of Enrollment Poland | 94 Participants | 48 Participants | 46 Participants |
| Sex: Female, Male Female | 52 Participants | 26 Participants | 26 Participants |
| Sex: Female, Male Male | 42 Participants | 22 Participants | 20 Participants |
| Stool consistency, Bristol scale | 1.6 units on a scale STANDARD_DEVIATION 0.9 | 1.5 units on a scale STANDARD_DEVIATION 1 | 1.7 units on a scale STANDARD_DEVIATION 0.9 |
| Stools per week | 1.6 Stools per week STANDARD_DEVIATION 0.5 | 1.6 Stools per week STANDARD_DEVIATION 0.5 | 1.6 Stools per week STANDARD_DEVIATION 0.5 |
| Withholding behavior | 85 Participants | 44 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 48 | 3 / 46 |
| serious Total, serious adverse events | 0 / 48 | 0 / 46 |
Outcome results
Primary
Number of Participants With Treatment Success (≥3 Spontaneous Defecations Per Week With no Fecal Soiling
Time frame: in the fourth week of the intervention
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lactobacillus Casei Rhamnosus Lcr35 | Number of Participants With Treatment Success (≥3 Spontaneous Defecations Per Week With no Fecal Soiling | 24 Participants |
| Placebo | Number of Participants With Treatment Success (≥3 Spontaneous Defecations Per Week With no Fecal Soiling | 28 Participants |
p-value: 0.39995% CI: [0.24, 1.5]risk analysis (prospective)
Secondary
Abdominal Pain at Week 1
Abdominal pain reported by child or symptoms of pain observed by parents. For single value median was calculated.
Time frame: during first weeks of intervention
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lactobacillus Casei Rhamnosus Lcr35 | Abdominal Pain at Week 1 | 0.0 abdominal pain episodes |
| Placebo | Abdominal Pain at Week 1 | 0.0 abdominal pain episodes |
p-value: 0.18595% CI: [0, 1]Wilcoxon (Mann-Whitney)
Secondary
Abdominal Pain at Week 4
Abdominal pain reported by child or symptoms of pain observed by parents. For single value median was calculated.
Time frame: during fourth weeks of intervention
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lactobacillus Casei Rhamnosus Lcr35 | Abdominal Pain at Week 4 | 0.0 abdominal pain episodes |
| Placebo | Abdominal Pain at Week 4 | 0.0 abdominal pain episodes |
p-value: 0.69895% CI: [0, 0]Wilcoxon (Mann-Whitney)
Secondary
Defecation Frequency at Week 1
Time frame: during first week of intervention
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lactobacillus Casei Rhamnosus Lcr35 | Defecation Frequency at Week 1 | 5.0 defecations per week |
| Placebo | Defecation Frequency at Week 1 | 6.0 defecations per week |
p-value: 0.00495% CI: [0, 2]Wilcoxon (Mann-Whitney)
Secondary
Defecation Frequency at Week 4
For single value median was calculated.
Time frame: during fourth week of intervention
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lactobacillus Casei Rhamnosus Lcr35 | Defecation Frequency at Week 4 | 4.0 defecations per week |
| Placebo | Defecation Frequency at Week 4 | 6.0 defecations per week |
p-value: 0.00595% CI: [0.5, 4]Wilcoxon (Mann-Whitney)
Secondary
Fecal Soiling Episodes at Week 1
Time frame: during first week of intervention
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lactobacillus Casei Rhamnosus Lcr35 | Fecal Soiling Episodes at Week 1 | 0.0 fecal soiling episodes |
| Placebo | Fecal Soiling Episodes at Week 1 | 0.0 fecal soiling episodes |
p-value: 0.70895% CI: [0, 0]Wilcoxon (Mann-Whitney)
Secondary
Fecal Soiling Episodes at Week 4
For single value median was calculated.
Time frame: during fourth week of intervention
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lactobacillus Casei Rhamnosus Lcr35 | Fecal Soiling Episodes at Week 4 | 0.0 fecal soiling episodes |
| Placebo | Fecal Soiling Episodes at Week 4 | 0.0 fecal soiling episodes |
p-value: 0.65995% CI: [0, 0]Wilcoxon (Mann-Whitney)
Secondary
Flatulence at Week 1
Flatulence reported by child or symptoms of pain observed by parents. For single value median was calculated.
Time frame: during first weeks of intervention
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lactobacillus Casei Rhamnosus Lcr35 | Flatulence at Week 1 | 0.0 episodes of flatulence |
| Placebo | Flatulence at Week 1 | 0.0 episodes of flatulence |
p-value: 0.64295% CI: [0, 0]Wilcoxon (Mann-Whitney)
Secondary
Flatulence at Week 4
Flatulence reported by child or symptoms of pain observed by parents. For single value median was calculated.
Time frame: during fourth weeks of intervention
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lactobacillus Casei Rhamnosus Lcr35 | Flatulence at Week 4 | 0.0 episodes of flatulence |
| Placebo | Flatulence at Week 4 | 0.0 episodes of flatulence |
p-value: 0.97395% CI: [0, 0]Wilcoxon (Mann-Whitney)
Secondary
Number of Defecations That Were Painful at Week 4
Pain reported by child or symptoms of pain observed by parents. For single value median was calculated.
Time frame: during fourth weeks of intervention
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lactobacillus Casei Rhamnosus Lcr35 | Number of Defecations That Were Painful at Week 4 | 0.0 painful defecations |
| Placebo | Number of Defecations That Were Painful at Week 4 | 0.0 painful defecations |
p-value: 0.7995% CI: [0, 0]Wilcoxon (Mann-Whitney)
Secondary
Number of Participants With Adverse Effects
Time frame: during 4 weeks of intervention
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lactobacillus Casei Rhamnosus Lcr35 | Number of Participants With Adverse Effects | 0 Participants |
| Placebo | Number of Participants With Adverse Effects | 3 Participants |
p-value: 0.116Wilcoxon (Mann-Whitney)
Secondary
Number of Participants With Use of Laxatives
Time frame: during 4 weeks of intervention
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lactobacillus Casei Rhamnosus Lcr35 | Number of Participants With Use of Laxatives | 18 Participants |
| Placebo | Number of Participants With Use of Laxatives | 10 Participants |
p-value: 0.1295% CI: [0.9, 6.2]risk analysis (prospective)
Secondary
Pain During Defecation at Week 1
Pain reported by child or symptoms of pain observed by parents. For single value median was calculated.
Time frame: during first weeks of intervention
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lactobacillus Casei Rhamnosus Lcr35 | Pain During Defecation at Week 1 | 0.0 painful defecations |
| Placebo | Pain During Defecation at Week 1 | 0.0 painful defecations |
p-value: 0.52295% CI: [-1, 1]Wilcoxon (Mann-Whitney)
Secondary
Stool Consistency at Week 1
Stool consistency scores were determined using the 7-point Bristol Stool Form Scale (1 for hard lumps to 7 for watery stools). For single value median was calculated.
Time frame: during first week of intervention
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lactobacillus Casei Rhamnosus Lcr35 | Stool Consistency at Week 1 | 3.6 units on a scale |
| Placebo | Stool Consistency at Week 1 | 3.9 units on a scale |
p-value: 0.61295% CI: [-0.6, 0.8]Wilcoxon (Mann-Whitney)
Secondary
Stool Consistency at Week 4
Stool consistency scores were determined using the 7-point Bristol Stool Form Scale (1 for hard lumps to 7 for watery stools). For single value median was calculated.
Time frame: during fourth week of intervention
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lactobacillus Casei Rhamnosus Lcr35 | Stool Consistency at Week 4 | 3.5 units on a scale |
| Placebo | Stool Consistency at Week 4 | 3.7 units on a scale |
p-value: 0.58995% CI: [-0.6, 0.7]Wilcoxon (Mann-Whitney)