Clinical trial NCT01260012: Antioxidant Supplements in the Reversal of Schistosomal Peri-portal Fibrosis
Official title: Study on the Role of Antioxidant Micronutrients on the Reversal of Schistosomal Peri-portal Fibrosis of the Liver.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Schistosomiasis
Liver Fibrosis
Periportal Fibrosis
Oxidative Stress
Keywords: Schistosoma mansoni
Schistosomiasis
periportal fibrosis
antioxidant
fibrosis reversal
Lead sponsor: Addis Ababa University
Sponsor class: OTHER
Collaborators: name: Ullevaal University Hospital
name: University of Oslo
name: University of Agder
name: Sorlandet Hospital HF
First posted: 2010-12-15
Enrollment: 414
Sex: ALL
Minimum age (years): 5
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Effect of antioxidant supplement on fibrosis reversal following praziquantel therapy
timeFrame: 2 years
Secondary outcomes:
measure: Time required for the reversal of schistosomal periportal fibrosis
timeFrame: 4 years
Other outcomes:
Locations:
city: Addis Ababa
country: Ethiopia
facility: Aklilu Lemma Institute of Pathobiology, Addis Ababa University
Study officials:
affiliation: Aklilu Lemma Institute of Pathobiology, Addis Ababa University
name: Nega Berhe, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Sorlandet Hospital HF, Box 416, 4604 Kristiansand - Norway
name: Svein G Gundersen, MD PhD
role: STUDY_DIRECTOR
affiliation: Ullevål University Hospital, Department of Infectious Diseases, Centre for Imported and Tropical Diseases, 0407 Oslo
name: Bjørn Myrvang, MD, PhD
role: STUDY_CHAIR
affiliation: Institute for Basic Medical Sciences, Department of Nutrition, University of Oslo, P.O.box 1046, N-0316 Oslo, Norway
name: Rune Blomhoff, MSc, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Berhe N, Halvorsen BL, Gundersen TE, Myrvang B, Gundersen SG, Blomhoff R. Reduced serum concentrations of retinol and alpha-tocopherol and high concentrations of hydroperoxides are associated with community levels of S. mansoni infection and schistosomal periportal fibrosis in Ethiopian school children. Am J Trop Med Hyg. 2007 May;76(5):943-9.
citation: El-Sokkary GH, Omar HM, Hassanein AF, Cuzzocrea S, Reiter RJ. Melatonin reduces oxidative damage and increases survival of mice infected with Schistosoma mansoni. Free Radic Biol Med. 2002 Feb 15;32(4):319-32. doi: 10.1016/s0891-5849(01)00753-5.
citation: Berhe N, Myrvang B, Gundersen SG. Reversibility of schistosomal periportal thickening/fibrosis after praziquantel therapy: a twenty-six month follow-up study in Ethiopia. Am J Trop Med Hyg. 2008 Feb;78(2):228-34.
citation: Karlsen A, Paur I, Bohn SK, Sakhi AK, Borge GI, Serafini M, Erlund I, Laake P, Tonstad S, Blomhoff R. Bilberry juice modulates plasma concentration of NF-kappaB related inflammatory markers in subjects at increased risk of CVD. Eur J Nutr. 2010 Sep;49(6):345-55. doi: 10.1007/s00394-010-0092-0. Epub 2010 Feb 2.
citation: Paur I, Austenaa LM, Blomhoff R. Extracts of dietary plants are efficient modulators of nuclear factor kappa B. Food Chem Toxicol. 2008 Apr;46(4):1288-97. doi: 10.1016/j.fct.2007.09.103. Epub 2007 Nov 5.
citation: Blomhoff R. Dietary antioxidants and cardiovascular disease. Curr Opin Lipidol. 2005 Feb;16(1):47-54. doi: 10.1097/00041433-200502000-00009.
citation: Eboumbou C, Steghens JP, Abdallahi OM, Mirghani A, Gallian P, van Kappel A, Qurashi A, Gharib B, De Reggi M. Circulating markers of oxidative stress and liver fibrosis in Sudanese subjects at risk of schistosomiasis and hepatitis. Acta Trop. 2005 May;94(2):99-106. doi: 10.1016/j.actatropica.2005.03.001. Epub 2005 Apr 7.
citation: Halliwell B. The antioxidant paradox. Lancet. 2000 Apr 1;355(9210):1179-80. doi: 10.1016/S0140-6736(00)02075-4. No abstract available.