Antioxidant Supplements in the Reversal of Schistosomal Peri-portal Fibrosis

Sponsor

Addis Ababa University (Other)

Overall Status

Unknown status

CT.gov ID

NCT01260012

Collaborator

Ullevaal University Hospital (Other), University of Oslo (Other), University of Agder (Other), Sorlandet Hospital HF (Other)

414

Enrollment

Location

Arms

Duration (Months)

5.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Schistosomiasis Liver Fibrosis Periportal Fibrosis Oxidative Stress	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	N/A

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

414 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jan 1, 2010

Anticipated Primary Completion Date :

Jun 1, 2013

Anticipated Study Completion Date :

Dec 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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	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. 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 Other Names: Interventional
Active Comparator: 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.	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.
No Intervention: 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.	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. Other Names: Placebo Praziquantel

Arm

Intervention/Treatment

Experimental: 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

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.

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

Other Names:

Interventional

Active Comparator: 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.

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.

No Intervention: 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.

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.

Other Names:

Placebo

Praziquantel

Outcome Measures

Primary Outcome Measures

Effect of antioxidant supplement on fibrosis reversal following praziquantel therapy [2 years]
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.

Secondary Outcome Measures

Time required for the reversal of schistosomal periportal fibrosis [4 years]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

5 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Aklilu Lemma Institute of Pathobiology, Addis Ababa University	Addis Ababa		Ethiopia	1176

Sponsors and Collaborators

Addis Ababa University
Ullevaal University Hospital
University of Oslo
University of Agder
Sorlandet Hospital HF

Investigators

Principal Investigator: Nega Berhe, MD, PhD, Aklilu Lemma Institute of Pathobiology, Addis Ababa University
Study Director: Svein G Gundersen, MD PhD, Sorlandet Hospital HF, Box 416, 4604 Kristiansand - Norway
Study Chair: Bjørn Myrvang, MD, PhD, Ullevål University Hospital, Department of Infectious Diseases, Centre for Imported and Tropical Diseases, 0407 Oslo
Principal Investigator: Rune Blomhoff, MSc, PhD, Institute for Basic Medical Sciences, Department of Nutrition, University of Oslo, P.O.box 1046, N-0316 Oslo, Norway