Clinical Evaluation of Ujiplus® Against Schistosoma Mansoni

Study Overview
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Brief Summary
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Schistosomiasis is classified as among the world's neglected tropical diseases (NTD). Morbidity due to Schistosoma mansoni (S. mansoni) is greatest among school-age children who typically have the highest burden of infection. In 2001, World Health Organization (WHO) passed a resolution for large-scale mass drug administration (MDA) using chemotherapy to deworm vulnerable children through school-based programs. While MDA has significantly contributed to reducing the burden of these infections, several concerns still exist over the large-scale use of chemotherapeutic drugs in deworming. The large population of children and the high frequency of dosage may pose a challenge to the sustainability of these programs. Further, the MDAs exert increasing drug pressure on parasite populations, a circumstance that is likely to favor parasite genotypes that can resist chemotherapy. Additionally, the current school-based MDA does not consider child malnutrition a very common malady in African countries. The greatest shortcoming is that currently approved S. mansoni chemotherapeutic treatment, Praziquantel is not recommended for children under six years of age due to its perceived toxicity. This excludes a highly vulnerable group from treatment. The above has called for alternative management options for S. mansoni among school and pre-school age children. The current study seeks to test the feasibility of the use of a nutritional supplement (Ujiplus®), as a potential deworming strategy against S. mansoni. Ujiplus® is a porridge flour fortified with papaya (Carica papaya) seeds extracts. In a previous study (NCT 027-25255), the product was found to have an effect on soil-transmitted helminths among a group of school children with no serious adverse events. We intend to evaluate the efficacy of Ujiplus® when given through school feeding programs and compare the outcome with praziquantel- the recommended MDA agent for deworming school children. The investigators will design and formulate the Ujiplus®, and test it among children in four primary schools in Mbita, Homabay county, Kenya.

Detailed Description
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Background: Schistosomiasis is classified as among the world's neglected tropical diseases (NTD). Morbidity due to Schistosoma mansoni (S.mansoni) is greatest among school-age children who typically have the highest burden of infection. In 2001, World Health Organization (WHO) passed a resolution for large-scale mass drug administration (MDA) using chemotherapy to deworm vulnerable children through school-based programs. While MDA has significantly contributed to reducing the burden of these infections, several concerns still exist over the large-scale use of chemotherapeutic drugs in deworming. The large population of children and the high frequency of dosage may pose a challenge to the sustainability of these programs. Further, the MDAs exert increasing drug pressure on parasite populations, a circumstance that is likely to favor parasite genotypes that can resist chemotherapy. Moreover, chemotherapeutic drugs are not recommended for children under the age of 6 years due to their toxicity, despite the fact that this is the age group most infected with S. mansoni. Additionally, the current school-based MDA does not consider child malnutrition a very common malady in African countries. Based on the above, we have designed a nutritional food supplement, Ujiplus®, with the potential as a homegrown mass drug administration tool against intestinal parasites including S.mansoni. Porridge (Uji) made from corn flour is one of the most prevalent traditional school meal snacks in developing countries. Because of its low cost, and popularity in schools, it has been adopted as a component in school meals, often prepared and given as a snack at break time. To enhance its effect, we have fortified the Uji flour with micronutrients and extracts from papaya (Carica papaya) seeds to form Ujiplus®. Carica papaya seeds have been found in various studies to have an anthelminthic effect with benzyl isothiocyanate (BITC) as the potential active ingredient. In a previous clinical trial, Ujiplus® reduced the Ascaris lumbricoides egg count by 63.9% after the two month period as compared to the albendazole arm, 78.8%. In this study, primary school children (ages 6-8) from four schools in Homabay County Kenya will be randomized into two arms: Children from two schools will receive 300 ml Ujiplus® porridge daily (test school), and the other two schools will receive a similar serving of plain porridge (cornflour and micronutrients only) with Praziquantel. Prior to the randomization, an initial baseline stool microscopy analysis will be done to determine the presence and intensity of intestinal worms. Core indicators of nutrition-height, weight, and hemoglobin counts-will also be assessed. The children will be monitored daily for three months and final stool sample analysis and clinical monitoring done at the end of the study. Baseline and follow-up data will be collected through Redcap software (Vanderbilt, Nashville, Tenn) analyzed and compared through the latest software of SAS statistical package.

Official Title
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Clinical Evaluation of Ujiplus®, a Porridge Snack With Deworming Properties for Activity Against Schistosoma Mansoni

Conditions
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Schistosoma Mansoni

Intervention / Treatment
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* Dietary Supplement: Ujiplus®
* Drug: Praziquantel 400mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Consenting parents and guardians Exclusion Criteria: Children with known allergy to papaya fruit products

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 8 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Dietary Supplement: Ujiplus Ujiplus flour, a nutritional supplement. The flour will be used to prepare porridge and each child is given a serving of 300 ml every school day for 90 days.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ujiplus® porridge<br>Arm receiving porridge fortified with dried papaya seeds (Ujiplus) | Dietary Supplement: Ujiplus®<br>* Ujiplus® flour, a nutritional supplement will be used to prepare porridge, and each child will be given a serving of 300 ml every school day for 90 days.<br>|
| Active Comparator: Praziquantel 400mg<br>Arm receiving the approved Praziquantel treatment of 400mg once with plain porridge daily (without papaya seeds) | Drug: Praziquantel 400mg<br>* 400mg of Praziquantel will be given to each child once at the beginning of the study and maize flour porridge fortified only with micronutrients cooked and served to each child, 300 ml per every school day for 90 days,<br>* Other names: Biltricide;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Parasite egg count | Parasitic eggs in a stool sample will be counted at the end of the intervention, using the Katz thick smear technique, and recorded as eggs per gram of faeces (EPG) | 90 days after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body Mass Index for age | Height, Weight and age will be collected. BMI will be calculated using WHO guidelines. | 90 days after intervention | 
| Class attendance | The class register used by the class teacher to record daily student attendance will be used to gather information on attendance, enrollment, and retention of students. | 90 days after randomization | 
| Haemoglobin levels | Blood sample will be taken for hemoglobin amounts at start and end of intervention | 90 days after randomization | 
| Number of children with Schistosoma mansoni | Number of children with Schistosoma mansoni will be recorded at start and end of intervention | 90 days after randomization |