Tolerability and Acceptability of Fibersol-2 in Children
Condition: Diarrhea
MeSH terms: Diarrhea
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      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: 
      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.
    

Intervention name(s): Fibersol-2
Intervention type(s): Combination Product
Intervention description(s): A placebo-controlled, randomized; double-blind 2 arm trial
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: A placebo-controlled, randomized
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Supportive Care
Keywords: Tolerability; Acceptability; Fibersol-2; Children