Antioxidant Supplements in the Reversal of Schistosomal Peri-portal Fibrosis

NCT01260012 | Unknown

• 1 other identifier: 2010/794-1
• Study Type: interventional
• Target: 414
• Locations: 1 country
• Sites: 1

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.

Conditions

Schistosomiasis; Liver Fibrosis; Periportal Fibrosis; Oxidative Stress

Keywords

Schistosoma mansoni; Schistosomiasis; periportal fibrosis; antioxidant; fibrosis reversal

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (1)

• Time required for the reversal of schistosomal periportal fibrosis

  4 years

Study Arms (3)

praziquantel+antioxidant

EXPERIMENTAL

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; Dietary Supplement: Praziquantel+antioxidant

Praziquantel +placebo 2mths then antioxidant for 10 months

ACTIVE COMPARATOR

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 with placebo supplement

NO INTERVENTION

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

Interventions

Praziquantel+antioxidant suppl 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

Praziquantel + placebo 2mths then antioxidant for 10 mths 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 +placebo 2mths then antioxidant for 10 months

Praziquantel therapy and placebo as supplement 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.

Also known as: Placebo, Praziquantel

Praziquantel therapy with placebo supplement

Praziquantel+antioxidant 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

Also known as: Interventional

praziquantel+antioxidant

Eligibility Criteria

• Age: 5 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Subjects with schistosomal periportal fibrosis will be eligible for the study

You may not qualify if:

• Subjects with acute malaria, tuberculosis or other chronic diseases such as diabetes mellitus, cardiovascular disease or cancer will be excluded from the study.

Sponsors & Collaborators

• Addis Ababa University: lead
• Ullevaal University Hospital: collaborator
• University of Oslo: collaborator
• University of Agder: collaborator
• Sorlandet Hospital HF: collaborator

Study Sites (1)

Aklilu Lemma Institute of Pathobiology, Addis Ababa University

Addis Ababa, Addis Ababa, 1176, Ethiopia

RECRUITING

Related 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.

  PMID: 17488920 BACKGROUND

• 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.

  PMID: 11841922 BACKGROUND

• 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.

  PMID: 18256420 BACKGROUND

• 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.

  PMID: 20119859 BACKGROUND

• 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.

  PMID: 17980947 BACKGROUND

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

  PMID: 15650563 BACKGROUND

• 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.

  PMID: 15814296 BACKGROUND

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

  PMID: 10791396 BACKGROUND

Related Links

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

MeSH Terms

Conditions

Schistosomiasis; Liver Cirrhosis

Interventions

Praziquantel; Methods

Condition Hierarchy (Ancestors)

Trematode Infections; Helminthiasis; Parasitic Diseases; Infections; Vector Borne Diseases; Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Investigative Techniques

Study Officials

• Nega Berhe, MD, PhD

  Aklilu Lemma Institute of Pathobiology, Addis Ababa University

  PRINCIPAL INVESTIGATOR

• Svein G Gundersen, MD PhD

  Sorlandet Hospital HF, Box 416, 4604 Kristiansand - Norway

  STUDY DIRECTOR

• Bjørn Myrvang, MD, PhD

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

  STUDY CHAIR

• Rune Blomhoff, MSc, PhD

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nega Berhe, MD, PHD

CONTACT

00251-911-408340; nega_berhe@yahoo.com

Svein Gunnar Gundersen, MD, PHD

CONTACT

0047 38074474; svein.g.gundersen@sshf.no

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: December 13, 2010
• First Posted: December 15, 2010
• Study Start: January 1, 2010
• Primary Completion: June 1, 2013
• Study Completion: December 1, 2015
• Last Updated: December 15, 2010

Record last verified: 2010-09

Locations

ET (1)