Tolerability and Acceptability of Fibersol-2 in Children

Study Overview
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Brief Summary
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Dietary fiber, a non-digestible carbohydrate, used in decades for the beneficial effect on health with physiological importance because such compounds have low energy values. These indigestible carbohydrates generally reach the large intestine undigested and unabsorbed, they are often used in many functional and/or low-calorie food and beverages. Researchers have stated that dietary fiber especially digestive-resistant maltodextrin has innumerable beneficial effects on human health, such as improving intestinal regularity by increasing fecal bulk, stimulating peristalsis and shortening gastrointestinal transit time. Resistant maltodextrin (Fibersol-2) is a low viscosity, water-soluble, indigestible dextrin produced by the treatment of corn starch with acid, enzymes, and heat. Dietary fiber, a non-digestible carbohydrate, has been used in decades for the beneficial effect of health with physiological importance. In developing countries most of the diarrhea episodes occur during the first two years of life and till date antibiotics have been found to have no role in over seventy five percent of young childhood diarrhea. Toddler's diarrhea which affects children aged 6 to 60 months is known as chronic nonspecific diarrhea of childhood. The stool is frequently watery or loose and may have food particles in it. Despite the diarrhea, the child continues to grow and gain weight, remains active and has a normal appetite. The beneficial effects of resistant maltodextrin are well known in developed countries; however, data are lacking in developing countries. It has become imperative to know its safety, tolerability and acceptability in small children with or without diarrhea in developing countries such as in Bangladesh.

Detailed Description
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To conduct an exploratory study to understand the digestive tolerability of resistant maltodextrin (Fibersol-2) in young healthy and diarrhea children aged 1-3 years for 30 children at home and 30 children at hospital in phase 1. Additionally, propose to conduct a placebo-controlled, randomized, double blind clinical trial to examine whether Fibersol-2 with water can reduce the duration of diarrhea and stool output in children of 1-3 years old in the tertiary level hospital. If the child vomits out within 10 minutes of oral intake, we will give him again similar amount of fibersol-2 for consumption after an hour of rejection; if the child vomits again within 10 minutes of next intake, we will stop giving him fibersol-2 anymore. Also assess the digestive tolerability of the study children. In addition to gathering information from hospital, field research staff will visit the households of study children to collect information about their health status by administering field tested questionnaire. Study staff members will follow-up the study participants round the clock (24 hrs) during their hospital stay. To ensure the patient care they maintain a roster duty with staff members consisting 2 Project Research Physicians, 4 Study Nurse, 2 Field Research Assistants and 4 Field Organizer. Project physician will be responsible for consenting as well as all clinical assessment including the assessment of the diarrheal patients and provide treatment, besides these they will be given treatment for other illness if needed, our study nurses are responsible for recording vital signs and will feed the Fibersol-2 to the study participants in front of their legal guardians at hospital and community level with appropriate dose and time. They will also be closely monitoring the participants after oral intake of fibersol-2; if any adverse event is observed they will call the study physician immediately. Field Research assistant and Field Organizer will be screening the community control as well as will record other socio-demographic information and anthropometry as required. Also assist the study nurse in monitoring the study participants at household level. Eligibility criteria for the clinical efficacy trial Inclusion criteria: (i) Children with acute watery diarrhea, 3 or more watery stool in any 24-hour period of <7 days duration with none or some dehydration (ii) Aged between 1-3 years, and (iii) Received written consent from parents Exclusion criteria: (i) Children with bloody diarrhea, severe diseases (severe sepsis, meningitis, severe pneumonia with respiratory distress requiring intensive care and ancillary support such as oxygen inhalation, orophryngeal suction etc., (ii) Child in a situation and could interfere with the optimal participation to the study or constitute a particular risk of non-compliance, (iii) Currently participating in another clinical trial, and (iv) Parents refused to give written consent. Methods for clinical efficacy trial A placebo-controlled, randomized; double-blind 2 arm trial to assess the efficacy of fibersol-2 in children with acute watery diarrhea. Children with acute watery diarrhea, 3 or more watery stool in any 24-hour period of <7 days duration with no dehydration. Study group 1, 46 will receive Fibersol-2 disolved in 50 ml drinking water, twice daily (suitable dose from the tolerability and acceptability trial) Study group 2, 46 will receive Placebo (regular maltodextrin) disolved in 50 ml drinking water twice daily (same dose as Fibersol-2) An experienced researcher at icddr,b, not involved in the study, will prepare the randomization list using the randomization table. The name of random allocation will be indicated on a slip of paper, kept inside the sealed envelope. The sealed envelopes will be supplied to the researcher to supply the intervention package. The children with no dehydration or some dehydration will be randomized immediately after admission. Baseline information Children fulfilling the eligibility criteria will stay in the hospital throughout the study period until discharged. Research physician will take a detailed medical history of the enrolled children to determine the duration of and type of diarrhoea and its frequency; duration and frequency of vomiting; and presence of other symptoms such as fever, feeding difficulties, and treatment received for the illness before admission; and perform a thorough physical examination including assessment of dehydration according to the guidelines used in icddr,b and also the nutritional status will be measured and recorded. Case management Dehydration will be assessed according to the modified WHO guidelines followed in the hospital. In children with some dehydration, the fluid deficit will be corrected with ORS in an amount 10 ml/kg/hour for the first hours, then 5 ml/kg/hr until the deficit is corrected. In addition, ongoing stool losses will be replaced with ORS 5-10 ml/kg after each watery stool. For high purging children, the ORS intake will be adjusted according to the ongoing stool loss. ORS therapy will continue until diarrhoea stops. Mothers will be advised to continue breastfeeding. Measurements Fluids intakes (IV, ORS, and water) ORS will be given to the after measuring with a calibrated cylinder and the amount intake will be recorded every 6 hours, in case of any leftover that will be deducted from previous order. Water intake will also be measured in a similar way. When needed IV fluid will be infused through a calibrated soluset, the amount infused will be recorded every 6 hours if the child requires IV fluid therapy. Output (stool, urine and vomitus) Stool will be collected in a bucket of known weight beneath the cholera cot with a central hole and will be measured every 6 hours with an electronic scale of a precision of 1 gram. Urine will be collected by pediatric urine collector (PUC bag) and measured with a calibrated cylinder in ml. Vomitus will be collected in a pre-weighed bowl and measured with an electronic scale. The children will be offered a defined food of known calorie after measuring with an electronic scale of precision 1 g. Any leftover will be measured and subtracted from the amount offered and amount ingested will be recorded every 6 hours. Nude body weight will be measured at admission, after rehydration, and every 6 hours until recovery from diarrhoea and then at the end of every 24 hours and at discharge. Clinical evaluation will be performed every morning and evening. Resolution of diarrhea will be defined as the passage of two consecutive soft/formed stools or no stool for 24 hours. Therapeutic success will be defined as the cessation of diarrhea within 7 days of inclusion in the study treatment. Duration of diarrhea will be calculated in hours from the time of randomization to the last watery or loose stool within 7 days. Children will be considered withdrawn from the study if their parents or legal guardian withdraw consent, or the child is withdrawn from study for treatment of any complications; data (intakes and outputs) of such children up to the time of withdrawal will be included in the analysis (intent to treat analysis). Data of the children who failed to recover within seven days (study period) will also be included in the analysis for a maximum of seven days; those will be labelled as therapeutic failures and will be treated in the hospital until recovery. Primary outcome measures will be; duration of diarrhea, proportion of patients recovered within 72 hours, and daily stool output. Definitions Abdominal distension occurs when substances, such as air (gas) or fluid, accumulate in the abdomen causing its outward expansion beyond the normal girth of the stomach and waist. It will be evaluated by regular measurement of abdominal girth. No set parameters for abdominal distension. To measure the abdominal girth before the IP and repeat measurement daily. If there is change that is increase in diameter of girth measurement then we will define distension. Recurrent abdominal pain or discomfort at least 3days/month in the last 3 months. [28, 29] Abdominal pain: Abdominal pain is felt in the part of the trunk below the ribs and above the pelvis. Abdominal pain comes from organs within the abdomen or organs adjacent to the abdomen. It will be measured by asking mother's perception whether the child had the history of cry, irritability which was associated with abdominal pain. [28] Rumbling: A stomach rumble, also known as a bowel sound or peristaltic sound, is a rumbling, growling or gurgling noise produced by movement of the contents of the gastro-intestinal tract as they are propelled through the small intestine by a series of muscle contractions called peristalsis. It will be measured both by taking history from the parents and by abdominal auscultation. Bloating: Bloating is the presence of abnormal general swelling, or increased in diameter of the abdominal area. Recurrent feeling of bloating or visible distension at least 3 days/month in the last 3 months [28]. It will also be evaluated by regular measurement of abdominal girth. Flatulence: flatus expelled through the anus or the quality or state of being flatulent, which is defined in turn as marked by or affected with gases generated in the intestine or stomach; likely to cause digestive flatulence. It will be measured by taking history from the parents. Stool consistency: Appearance of the stool; such as formed, mucoid, or liquid. This will be measured by direct visualization by the parents as well treating physicians.

Official Title
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Tolerability and Acceptability of Fibersol-2 (Resistant Maltodextrin) in Healthy and Diarrheal Children Followed by a Randomized Clinical Trial to Evaluate the Efficacy of Fibersol-2 in Diarrheal Children 1-3 Years Old

Conditions
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Diarrhea

Intervention / Treatment
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* Combination Product: Fibersol-2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children with acute watery diarrhea, 3 or more watery stool in any 24-hour period of <7 days duration with none or some dehydration Aged between 1-3 years, and Received written consent from parents Exclusion Criteria: Children with bloody diarrhea, severe diseases (severe sepsis, meningitis, severe pneumonia with respiratory distress requiring intensive care and ancillary support such as oxygen inhalation, orophryngeal suction etc. Child in a situation and could interfere with the optimal participation to the study or constitute a particular risk of non-compliance Currently participating in another clinical trial, and Parents refused to give written consent.

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 3 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
Interventional Model Description: A placebo-controlled, randomized
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Fibersol-2<br>Receive Fibersol-2 twice daily | Combination Product: Fibersol-2<br>* A placebo-controlled, randomized; double-blind 2 arm trial<br>|
| Placebo Comparator: Placebo<br>Receive placebo twice daily | Combination Product: Fibersol-2<br>* A placebo-controlled, randomized; double-blind 2 arm trial<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of diarrhea | Main outcome measure is duration of diarrhea | 72 hours | 
| Stool consistency. | Stool consistency measured by regular observation | 24 hrs | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fibersol-2, Children, Tolerability, Acceptability