Clinical trial NCT03639142: Dried Plums (Prunes) vs. Polyethylene Glycol 4000 for Treatment of Functional Constipation in Children
Official title: Dried Plums (Prunes) vs. Polyethylene Glycol 4000 for Treatment of Functional Constipation in Children - Randomised Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Functional Constipation
Keywords: constipation, prunes, children
Lead sponsor: Medical University of Warsaw
Sponsor class: OTHER
First posted: 2018-08-20
Enrollment: 110
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Children with functional constipation according to the Rome IV criteria will be randomly assigned to receive prunes at dose 3.5 g/kg/d (prune group) or Polyethylene Glycol 4000 (PEG group) at dose 0.5 g/kg/d for 4 weeks. Before treatment children with impaction will receive PEG 4000 at the dose 1.5 g/kg for 3-5 consecutive days. The primary outcome measure will be treatment success, defined as ≥3 BM per week with no fecal soiling during last week of the intervention.

Detailed description: We will conduct a randomized open-label trial at the Department of Paediatrics of the Medical University of Warsaw. The trial will be initiated by the investigators and conducted independently of any commercial entities. The aim will be to assess the effectiveness of dried prunes in the management of functional constipation in children in comparison to PEG 4000. Patients will be included into our study when functional constipation will be diagnosed according to ROME IV criteria. Those patients which will meet inclusion criteria will be assigned randomly to receive prunes at dose 3,5 g/kg/d in three portions a day, for 4 weeks (amount of prescribed prunes will be calibrated with the weight that child ought to have on WHO growth charts at 50th percentile) or PEG 4000 at dose 0,5 g/kg/d once daily orally, for 4 weeks. Parents of the children allocated to the prunes group will receive written information from dietician how to introduce prunes into child's diet (i.e. prunes should be introduced every day in three meals; prunes can be chopped or grinded before eating them; prunes can be eaten alone or child may eat them as a part of bigger meal (which is prefered version); prunes can be introduced with yoghurt, cereals, nuts and seeds as a morning meal). All patients will be asked to discontinue any laxatives if they used them previously. In case of rectal impaction noted on physical examination, PEG 4000 at dose of 1.5 g/kg for 3-5 consecutive days will be recommended. All subjects parents will receive a stool diary to record the frequency of bowel movements; stool consistency according to Bristol Stool Form Scale (which refers to 7 pictures of different forms of stool; 1 for hard lumps to 7 for watery stools); frequency of episodes of fecal soiling, pain during defecation, or abdominal pain or flatulence; use of additional laxative treatment; and adverse effects during the 4 weeks of the intervention. All patients or their parents (if child is too young) will be asked to write down selfreported 3 day food diaries on non-consecutive days, 2 d during the week and 1 d during the weekend to assess fiber intake during the study period .. All patients will be informed of rescue therapy -when there will be no defecation for 3 consecutive days during ongoing trail, PEG 4000 will be allowed at the dose of 1.5 g/kg/d until the child will pass a stool.

During the study period, every week investigator will call the patients parents to assess compliance with the study protocol.

Second visit will take place at the end of the trial (4th week). During this visit, investigators will collect stool diaries. Prunes used in the study will be purchased by parents of the children. It will be advised for parents to buy prunes under the trade mark of "Makar" in order to avoid product composition variability bias. Choice of the trade mark was taken considering the price of a product.

This study is designed as a randomized, open label controlled trial with 1:1 allocation. In order to obtain comparable groups, block randomisation will be performed (each block will contain four patients: two in the intervention group and two in the control group). The randomisation list will be generated using the statistical program StatsDirect by an independent person and will be kept by a staff member not involved in the trial.

Based on available data in the literature, we assume that a clinically significant difference in the effectiveness is 15%. To detect such a difference between the study groups with a power of 80% and alpha of 5%, a sample of 100 children is needed. Assuming approximately 10% loss to follow-up, we aim to recruit a total of 110 children for this study.

The Ethical Committee of the Medical University of Warsaw will be asked for approval for the study before recruitment commenced. Any modifications to the protocol that may affect the conduct of the study will be presented to the Ethical Committee. Verbal and written information regarding informed consent will be presented to the caregivers.

All analysis will be conducted on an intention-to-treat basis, including all patients in the groups to which they are randomized for whom outcomes are available (including drop-outs and withdrawals). Descriptive statistics will be used to summarize baseline characteristics. The Student t test will be used to compare mean values of continuous variables for approximating a normal distribution. For non normally distributed variables, the Mann-Whitney U test will be used. The chi-square or Fisher exact test will be used, when appropriate, to compare percentages. For continuous outcomes, differences in means or differences in medians (depending on the distribution of the data), and for dichotomous outcomes, the RR and number needed to treat, all with a 95% CI, will be calculated. The difference between study groups will be considered significant when the 95% CI for RR does not include 1.0, or when the 95% CI for MD does not include 0. All statistical tests will be 2-tailed and performed at the 5% level of significance.

Eligibility criteria: Inclusion Criteria:

* children with constipation diagnosed with ROME IV criteria

Exclusion Criteria:

* diagnosis of irritable bowel syndrome, mental retardation, endocrine disease (eg, Hyperthyroidism), an organic cause of defecation disorders (eg, Hirshsprung disease, spinal anomalies, anorectal pathology, a history of gastrointestinal surgery), functional nonretentive fecal incontinence, or intake of medications influencing gastrointestinal motility

Primary outcomes:
measure: The primary outcome measure will be treatment success
timeFrame: up to 4 weeks
Secondary outcomes:
measure: stool consistency (according to the Bristol Stool Form Scale) during whole study period
timeFrame: up to 4 weeks
measure: frequency of defecation per week
timeFrame: up to 4 weeks
measure: frequency of fecal soiling per week
timeFrame: up to 4 weeks
measure: frequency of pain during defecation per week
timeFrame: up to 4 weeks
measure: frequency of abdominal pain or flatulence per week
timeFrame: up to 4 weeks
measure: need for intake of additional laxative treatment during whole study period
timeFrame: up to 4 weeks
measure: adverse events
timeFrame: up to 4 weeks
Other outcomes:
Locations:
Study officials:
References:
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