Antioxidant Supplements in the Reversal of Schistosomal Peri-portal Fibrosis

Oxidative Stress Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01260012
• Other study ID #: 2010/794-1
• Status: Recruiting
• Phase: N/A
• First received: December 13, 2010
• Last updated: December 14, 2010
• Start date: January 2010
• Est. completion date: December 2015

Study information

• Verified date: September 2010
• Source: Addis Ababa University
• Contact: Nega Berhe, MD, PHD
• Phone: 00251-911-408340
• Email: nega_berhe[@]yahoo.com
• Is FDA regulated: No
• Health authority: Ethiopia: Ethiopia Science and Technology CommissionNorway: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 414
• Est. completion date: December 2015
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 5 Years to 60 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Fibrosis
• Liver Fibrosis
• Oxidative Stress
• Periportal Fibrosis
• Schistosomiasis

Intervention

Dietary Supplement:
• Praziquantel+antioxidant suppl
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.

Other:
• Praziquantel + placebo 2mths then antioxidant for 10 mths
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.

Dietary Supplement:
• Praziquantel therapy and placebo as supplement
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.
• Praziquantel+antioxidant
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

Locations

Country	Name	City	State
Ethiopia	Aklilu Lemma Institute of Pathobiology, Addis Ababa University	Addis Ababa

Sponsors (5)

Lead Sponsor	Collaborator
Addis Ababa University	Oslo University Hospital Ulleval, Sorlandet Hospital HF, University of Agder, University of Oslo

Country where clinical trial is conducted

Ethiopia, 

References & Publications (8)

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. — View 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. — View Citation

Blomhoff R. Dietary antioxidants and cardiovascular disease. Curr Opin Lipidol. 2005 Feb;16(1):47-54. Review. — View 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. Epub 2005 Apr 7. — View 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. — View Citation

Halliwell B. The antioxidant paradox. Lancet. 2000 Apr 1;355(9210):1179-80. Review. — View Citation

Karlsen A, Paur I, Bøhn 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. — View 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. Epub 2007 Nov 5. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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	No

External Links

•   Financial support for the research project was obtained from Ulleval hospital, Centre for Imported and Tropical Diseases