Clinical trial NCT04679831: Clinical Evaluation of Ujiplus® Against Schistosoma Mansoni
Official title: Clinical Evaluation of Ujiplus®, a Porridge Snack With Deworming Properties for Activity Against Schistosoma Mansoni
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Schistosoma Mansoni
Lead sponsor: Kenya Medical Research Institute
Sponsor class: OTHER
Collaborators: name: Kanazawa University
First posted: 2020-12-22
Enrollment: 400
Sex: ALL
Minimum age (years): 6
Maximum age (years): 8
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

* Consenting parents and guardians

Exclusion Criteria:

* Children with known allergy to papaya fruit products

Primary outcomes:
measure: Parasite egg count
timeFrame: 90 days after randomization
Secondary outcomes:
measure: Body Mass Index for age
timeFrame: 90 days after intervention
measure: Class attendance
timeFrame: 90 days after randomization
measure: Haemoglobin levels
timeFrame: 90 days after randomization
measure: Number of children with Schistosoma mansoni
timeFrame: 90 days after randomization
Other outcomes:
Locations:
city: Mbita
country: Kenya
facility: Mbita
Study officials:
affiliation: Kenya Medical Research Institute
name: Elijah M Songok, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Avila S, Kugo M, Silveira Hornung P, Apea-Bah FB, Songok EM, Beta T. Carica papaya seed enhances phytochemicals and functional properties in cornmeal porridges. Food Chem. 2020 Apr 15;323:126808. doi: 10.1016/j.foodchem.2020.126808. Online ahead of print.
citation: Kugo M, Keter L, Maiyo A, Kinyua J, Ndemwa P, Maina G, Otieno P, Songok EM. Fortification of Carica papaya fruit seeds to school meal snacks may aid Africa mass deworming programs: a preliminary survey. BMC Complement Altern Med. 2018 Dec 7;18(1):327. doi: 10.1186/s12906-018-2379-2.
citation: Okeniyi JA, Ogunlesi TA, Oyelami OA, Adeyemi LA. Effectiveness of dried Carica papaya seeds against human intestinal parasitosis: a pilot study. J Med Food. 2007 Mar;10(1):194-6. doi: 10.1089/jmf.2005.065.
citation: Kermanshai R, McCarry BE, Rosenfeld J, Summers PS, Weretilnyk EA, Sorger GJ. Benzyl isothiocyanate is the chief or sole anthelmintic in papaya seed extracts. Phytochemistry. 2001 Jun;57(3):427-35. doi: 10.1016/s0031-9422(01)00077-2.
citation: Sapaat A, Satrija F, Mahsol HH, Ahmad AH. Anthelmintic activity of papaya seeds on Hymenolepis diminuta infections in rats. Trop Biomed. 2012 Dec;29(4):508-12.