Effectiveness of Folic Acid Supplementation in Acute Watery Diarrhea Among Children Under 5 Years of Age

Study Overview
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Brief Summary
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Folic acid is a palatable and easily available drug with no serious adverse effects. L-methylfolate is its biologically activated form and is preferred because of its direct availability for certain metabolic processes. As there is no specific and safe drug available that may help in decreasing the duration of diarrhea, purging rate or consistency of stools; and having known the theoretical benefits of folic acid in this regard, it would be appropriate to assess the effectiveness of L-methylfolate among children with diarrhea.

Detailed Description
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After approval from the Institutional Review Board of King Edward Medical University, Mayo Hospital, Lahore, all children diagnosed with acute watery diarrhea as per operational definition fulfilling the inclusion criteria, presenting to the Department of Pediatrics, Mayo Hospital, will be enrolled in this study. Informed written consent will be taken from the parents/guardians of all participants. A detailed history and examination of each subject would be done by an investigator at presentation. Patients will be randomized in two groups - A and B by lottery method. There will be 162 patients in each group. The treatment regimen that includes breast feeding, nutritional advice, rehydration plan; ORT by low osmolar ORS or intravenous rehydration (if required) and zinc sulphate will be given according to the WHO guidelines to all patients of both groups. Children under 1 year of age in group A will receive 3 drops (90mcg) of L-methylfolate calcium) while those older than 1 year of age will be given 5 drops (150mcg). Subjects in Group B will receive equal amount of distilled water as placebo (i.e. 3 drops to <1yr age and 5 drops to >1 yr. Frequency and grades of loose stools in both groups will be assessed daily and written down on a predesigned proforma.

Official Title
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Effectiveness of Folic Acid Supplementation in Acute Watery Diarrhea Among Children Under 5 Years of Age

Conditions
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Diarrhoea;Acute

Intervention / Treatment
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* Drug: L-Methylfolate Calcium


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children aged 2months- 5 years Both genders Acute watery diarrhea as per operational definition Diarrhea of less than 7-day duration Exclusion Criteria: Severely malnourished children <3 SD Bloody diarrhea Prolonged (7-14 days duration), persistent (>14 days duration) or chronic diarrhea (>4weeks duration) Those who received folic acid within the last 14 days Hospital-acquired diarrhea (diarrhea occurring after 48hrs of stay in hospital) Antibiotic-associated diarrhea. Presence of other co morbid conditions like pneumonia, sepsis, meningitis, etc.

Ages Eligible for Study
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Minimum Age: 2 Months
Maximum Age: 5 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: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: L-methylfolate supplementation<br>Children under 1 year of age in group A will receive 3 drops (90mcg) of L-methylfolate calcium) while those older than 1 year of age will be given 5 drops (150mcg) daily fior 5 days | Drug: L-Methylfolate Calcium<br>* Folic acid is one of the water-soluble B vitamins, which is synthetically-produced and found in fortified foods and supplements. It is essential for the synthesis and repair of DNA and RNA and metabolism of amino acids which are required for cell division. There is damage to the intestinal mucosa in most diarrhea cases; therefore, the role of folic acid has been studied as adjuvant therapy for diarrhea since folic acid plays an important role in the synthesis of DNA especially in rapidly regenerating cells.<br>|
| Placebo Comparator: distilled water<br>Subjects in Group B will receive equal amount of distilled water as placebo (i.e. 3 drops to <1yr age and 5 drops to >1 yr. | Drug: L-Methylfolate Calcium<br>* Folic acid is one of the water-soluble B vitamins, which is synthetically-produced and found in fortified foods and supplements. It is essential for the synthesis and repair of DNA and RNA and metabolism of amino acids which are required for cell division. There is damage to the intestinal mucosa in most diarrhea cases; therefore, the role of folic acid has been studied as adjuvant therapy for diarrhea since folic acid plays an important role in the synthesis of DNA especially in rapidly regenerating cells.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changing the frequency of stools | L-methylfolate supplementation is effective in changing the frequency of stools. It will be measured in episodes per day | 5 days | 
| Effectiveness in improving grades of diarrhea | L-methylfolate supplementation is effective in changing grades of diarrhea. WHO grades will be taken as reference | 5 days | 
| Effectiveness in changing duration of diarrhea | L-methylfolate supplementation is effective in changing duration of diarrhea in days. | 5 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acute watery diarrhea, folic acid, L-methylfolate