Antioxidant Supplements in the Reversal of Schistosomal Peri-portal Fibrosis

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2010 by Addis Ababa University
Sponsor:
Collaborators:
Oslo University Hospital Ulleval
University of Oslo
University of Agder
Sorlandet Hospital HF
Information provided by:
Addis Ababa University
ClinicalTrials.gov Identifier:
NCT01260012
First received: December 13, 2010
Last updated: December 14, 2010
Last verified: September 2010
  Purpose

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 Intervention
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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Study on the Role of Antioxidant Micronutrients on the Reversal of Schistosomal Peri-portal Fibrosis of the Liver.

Resource links provided by NLM:


Further study details as provided by Addis Ababa University:

Primary Outcome Measures:
  • Effect of antioxidant supplement on fibrosis reversal following praziquantel therapy [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 414
Study Start Date: January 2010
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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

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

Ages Eligible for Study:   5 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01260012

Contacts
Contact: Nega Berhe, MD, PHD 00251-911-408340 nega_berhe@yahoo.com
Contact: Svein Gunnar Gundersen, MD, PHD 0047 38074474 svein.g.gundersen@sshf.no

Locations
Ethiopia
Aklilu Lemma Institute of Pathobiology, Addis Ababa University Recruiting
Addis Ababa, Ethiopia, 1176
Contact: Nega Berhe, Md PhD    00251-911-408340    nega_berhe@yahoo.com   
Principal Investigator: Nega Berhe, MD, PhD         
Sponsors and Collaborators
Addis Ababa University
Oslo University Hospital Ulleval
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
  More Information

Additional Information:
Publications:

Responsible Party: Dr Nega Berhe, Aklilu Lemma Institute of Pathobiology, Addis Ababa Ethiopia
ClinicalTrials.gov Identifier: NCT01260012     History of Changes
Other Study ID Numbers: 2010/794-1
Study First Received: December 13, 2010
Last Updated: December 14, 2010
Health Authority: Ethiopia: Ethiopia Science and Technology Commission
Norway: Ethics Committee

Keywords provided by Addis Ababa University:
Schistosoma mansoni
Schistosomiasis
periportal fibrosis
antioxidant
fibrosis reversal

Additional relevant MeSH terms:
Fibrosis
Schistosomiasis
Liver Cirrhosis
Pathologic Processes
Trematode Infections
Helminthiasis
Parasitic Diseases
Liver Diseases
Digestive System Diseases
Antioxidants
Praziquantel
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protective Agents
Physiological Effects of Drugs
Anthelmintics
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 31, 2014