Antioxidant Supplements in the Reversal of Schistosomal Peri-portal Fibrosis

Study Overview
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Brief Summary
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Liver fibrosis is the most serious complication of schistosomiasis mansoni. However only limited proportion of subjects with infection develop this pathology and there is limited knowledge on risk factors for the differential morbidity patterns observed in endemic communities. Our preliminary cross-sectional study indicated that serum levels of antioxidants may be related with the development of fibrosis. The present project is a randomised double blinded placebo controlled prospective study investigating the role of food based antioxidant supplements on the outcome of anti-schistosomal chemotherapy with regards to the extent of fibrosis reversal.

Detailed Description
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Schistosomiasis is the second leading parasitic disease worldwide, after malaria. Liver fibrosis is the most serious complication of schistosomiasis mansoni which can lead to reduced work capacity and early death in endemic countries. There is, however, limited knowledge on the development of liver fibrosis and the differential patterns morbidity observed in endemic communities. Our preliminary cross-sectional study in Ethiopia seems to indicate that serum levels of antioxidants may influence the development of fibrosis. The present project is a translational study combining basic antioxidant laboratory work with is a randomised double blinded placebo controlled prospective study in endemic areas in Ethiopia, investigating the role of food based antioxidant supplements on the outcome of anti-schistosomal chemotherapy with regards to the extent of fibrosis reversal. In addition, analysis of dietary intakes of antioxidants among communities with comparable levels of S. mansoni infection but with differing levels of schistosomal periportal fibrosis will be undertaken to compare serum levels of antioxidants and prevalence of liver fibrosis. Furthermore we plan to assess development of schistosomal peri-portal fibrosis in a cohort of students established 9 years back who had comparable levels of community prevalence of schistosomiasis but with differing access to fruits and vegetables. Research on this topic has a high priority globally which is in line with the millennium development goals. Knowledge in this field will also add to our understanding of fibrosis development in general and to the efficacy of clinical treatment of schistosomiasis in particular.

Official Title
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Study on the Role of Antioxidant Micronutrients on the Reversal of Schistosomal Peri-portal Fibrosis of the Liver.

Conditions
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Schistosomiasis, Liver Fibrosis, Periportal Fibrosis, Oxidative Stress

Intervention / Treatment
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* Dietary Supplement: Praziquantel+antioxidant suppl
* Other: Praziquantel + placebo 2mths then antioxidant for 10 mths
* Dietary Supplement: Praziquantel therapy and placebo as supplement
* Dietary Supplement: Praziquantel+antioxidant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with schistosomal periportal fibrosis will be eligible for the study Exclusion Criteria: Subjects with acute malaria, tuberculosis or other chronic diseases such as diabetes mellitus, cardiovascular disease or cancer will be excluded from the study.

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 60 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: Single Group Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: praziquantel+antioxidant<br>Praziquantel therapy will be offered at the start, at six weeks and at 12 weeks from date of enrollment. Thereafter praziquantel therapy will be offered if subjects have demonstrable S. mansoni eggs on the subsequent six-monthly evaluations. In additions, antioxidant suppliment will be given daily for a period of one year | Dietary Supplement: Praziquantel+antioxidant suppl<br>* Praziquantel therapy will be offered at the start, at six weeks and at 12 weeks from date of enrollment. Thereafter praziquantel therapy will be offered if subjects have demonestrable S. mansoni eggs on the subsequent six-monthly evaluations. In addition subjects will receive antioxidant supplement on daily basis for a period of one year.<br>Dietary Supplement: Praziquantel+antioxidant<br>* Praziquantel treatment will be offered at time 0, six weeks and 12 weeks from the start. Antioxidant supplement will be offered on a daily basis for a period of one year<br>* Other names: Interventional;|
| Active Comparator: Praziquantel +placebo 2mths then antioxidant for 10 months<br>Praziquantel therapy will be offered at the start, at six weeks and at 12 weeks from date of enrollment. Thereafter praziquantel therapy will be offered if subjects have demonstrable S. mansoni eggs on the subsequent six-monthly evaluations. In addition subjects will receive placebo as a supplement for two months which will be followed by antioxidant as a supplement for the rest of the year. | Other: Praziquantel + placebo 2mths then antioxidant for 10 mths<br>* Praziquantel therapy will be offered at the start, at six weeks and at 12 weeks from date of enrollment. Thereafter praziquantel therapy will be offered if subjects have demonestrable S. mansoni eggs on the subsequent six-monthly evaluations. In addition subjects will receive placebo as a supplement for two months which will be followed by antioxidant as a supplement for the rest of the year.<br>|
| No Intervention: Praziquantel therapy with placebo supplement<br>Praziquantel therapy will be offered at the start, at six weeks and at 12 weeks from date of enrollment. Thereafter praziquantel therapy will be offered if subjects have demonstrable S. mansoni eggs on the subsequent six-monthly evaluations. In addition subjects will receive placebo as a supplement for a period of one year. | Dietary Supplement: Praziquantel therapy and placebo as supplement<br>* Praziquantel at day 0, 6-weeks and at 12 weeks from start of study. Thereafter praziquantel therapy will be offered if subjects have demonestrable s.mansoni eggs on six-monthly evaluation periods. Placebo will be given as a supplement for one year.<br>* Other names: Praziquantel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of antioxidant supplement on fibrosis reversal following praziquantel therapy | Patients schistosomal periportal fibrosis will be treated with praziquantel at the start, at six weeks and at 3 months from the start of the study. Praziquantel therapy will then be offered if subjects have demonstrable S. mansoni eggs on six-monthly evaluation periods. In addition, one group will recieve supplemental antioxidant for one year, the second group will recieve supplement as a placebo for two months and then antioxidant suppliment for 10 months, the third group will receive placebo as a supplement for one year. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time required for the reversal of schistosomal periportal fibrosis | Subjects will be followed with six-monthly evaluations for a period of 4 years and praziquantel therapy will be offered if subjects have demonstrable S. mansoni eggs on the six-monthly evaluations. Over the four year period we plan to assess the time required for the reversal of the various stages of schistosomal periportal fibrosis. | 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schistosoma mansoni, Schistosomiasis, periportal fibrosis, antioxidant, fibrosis reversal