Antioxidant Supplements in the Reversal of Schistosomal Peri-portal Fibrosis

NCT ID: NCT01260012

Last Updated: 2010-12-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

414 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-01-31

Study Completion Date

2015-12-31

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.

Conditions

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Schistosomiasis Liver Fibrosis Periportal Fibrosis Oxidative Stress

Keywords

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Schistosoma mansoni Schistosomiasis periportal fibrosis antioxidant fibrosis reversal

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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praziquantel+antioxidant

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

Group Type EXPERIMENTAL

Praziquantel+antioxidant suppl

Intervention Type DIETARY_SUPPLEMENT

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.

Praziquantel+antioxidant

Intervention Type DIETARY_SUPPLEMENT

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

Praziquantel +placebo 2mths then antioxidant for 10 months

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.

Group Type ACTIVE_COMPARATOR

Praziquantel + placebo 2mths then antioxidant for 10 mths

Intervention Type OTHER

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.

Praziquantel therapy with placebo supplement

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.

Group Type NO_INTERVENTION

Praziquantel therapy and placebo as supplement

Intervention Type DIETARY_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.

Interventions

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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.

Intervention Type DIETARY_SUPPLEMENT

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.

Intervention Type OTHER

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.

Intervention Type DIETARY_SUPPLEMENT

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

Intervention Type DIETARY_SUPPLEMENT

Other Intervention Names

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Placebo Praziquantel Interventional

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.
Minimum Eligible Age

5 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ullevaal University Hospital

OTHER

Sponsor Role collaborator

University of Oslo

OTHER

Sponsor Role collaborator

University of Agder

OTHER

Sponsor Role collaborator

Sorlandet Hospital HF

OTHER_GOV

Sponsor Role collaborator

Addis Ababa University

OTHER

Sponsor Role lead

Responsible Party

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Aklilu Lemma Institute of Pathobiology, Addis Ababa Ethiopia

Principal Investigators

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Nega Berhe, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Aklilu Lemma Institute of Pathobiology, Addis Ababa University

Svein G Gundersen, MD PhD

Role: STUDY_DIRECTOR

Sorlandet Hospital HF, Box 416, 4604 Kristiansand - Norway

Bjørn Myrvang, MD, PhD

Role: STUDY_CHAIR

Ullevål University Hospital, Department of Infectious Diseases, Centre for Imported and Tropical Diseases, 0407 Oslo

Rune Blomhoff, MSc, PhD

Role: PRINCIPAL_INVESTIGATOR

Institute for Basic Medical Sciences, Department of Nutrition, University of Oslo, P.O.box 1046, N-0316 Oslo, Norway

Locations

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Aklilu Lemma Institute of Pathobiology, Addis Ababa University

Addis Ababa, Addis Ababa, Ethiopia

Site Status RECRUITING

Countries

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Ethiopia

Central Contacts

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Nega Berhe, MD, PHD

Role: CONTACT

Phone: 00251-911-408340

Email: [email protected]

Svein Gunnar Gundersen, MD, PHD

Role: CONTACT

Phone: 0047 38074474

Email: [email protected]

Facility Contacts

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Nega Berhe, Md PhD

Role: primary

References

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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.

Reference Type BACKGROUND
PMID: 17488920 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11841922 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18256420 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20119859 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17980947 (View on PubMed)

Blomhoff R. Dietary antioxidants and cardiovascular disease. Curr Opin Lipidol. 2005 Feb;16(1):47-54. doi: 10.1097/00041433-200502000-00009.

Reference Type BACKGROUND
PMID: 15650563 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15814296 (View on PubMed)

Halliwell B. The antioxidant paradox. Lancet. 2000 Apr 1;355(9210):1179-80. doi: 10.1016/S0140-6736(00)02075-4. No abstract available.

Reference Type BACKGROUND
PMID: 10791396 (View on PubMed)

Related Links

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http://ulleval.no

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

Other Identifiers

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2010/794-1

Identifier Type: -

Identifier Source: org_study_id