Response Modifier (Arabinoxylan Rice Bran/MGN-3/Biobran) With Interferon-Alpha for HCV

Hepatitis C, Chronic Clinical Trial

Official title:

Clinical Study of a Biological Response Modifier (Arabinoxylan Rice Bran/MGN-3/Biobran) With Interferon-Alpha for the Treatment of Hepatitis C Infection

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02690103
• Other study ID #: 3
• Status: Completed
• Phase: Phase 2
• First received: February 8, 2016
• Last updated: February 23, 2016
• Start date: July 2012
• Est. completion date: June 2015

Study information

• Verified date: February 2016
• Source: Cairo University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Egypt: Ministry of Health and Population
• Study type: Interventional

Clinical Trial Summary

Current treatments for Hepatitis C virus (HCV) have severe side effects and are very expensive. There is a need to explore effective natural therapies against HCV that are less toxic and more cost-effective.

37 chronic HCV infected patients were randomized into two groups and treated with PEG interferon plus ribavirin for the first group or Biobran, an arabinoxylan from rice bran (1 g/day) for the second group. Viremia level, liver enzymes, γ-interferon (IFN-γ) levels in serum, and toxicity were checked before and three months after treatment.

Description:

The current study is a preliminary investigation of whether Biobran has the ability to restrict viremia in patients with chronic HCV or not. In addition, we examined the effect of Biobran on liver enzymes and inflammation as well as assessing any side effects of Biobran. Results show that treatment with Biobran resulted in a significant reduction in the viral load, an increase in liver enzymes, and patients reported good health.

For the randomized trial, we selected 37 patients who had been admitted to El-Kasr El-Aini Hospital at Cairo, Egypt. The patients had been diagnosed with genotype 4 HCV infection. The study was approved by Cairo University Hospital, Cairo, Egypt and by IRB at Charles Drew school of medicine and Science, Los Angeles, CA, USA. The study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in the prior approval by Cairo University, El-Kasr El-Aini Hospital, Cairo, Egypt and by the Institutional Review Board (IRB) at Cairo University, Egypt and Charles R Drew University (CDU), Los Angeles, CA., USA.

Thirty-seven patients of both sexes (23 males and 14 females) with HCV (genotype 4), between the ages of 15 and 69, participated in the current study. Informed consent was obtained from all participants.

The patients were divided randomly into two groups: the Biobran group and the PEG interferon plus ribavirin (control) group . Prior to treatment, clinical characteristics were determined for the patients in each group. The clinical characteristics of the HCV patients were investigated for hepatitis C, alpha-fetoprotein (AFP) levels, total leucocyte count (TLC), Platelet (PLT) count, Hemoglobin (Hb) levels, triglyceride (TG) levels, glycated hemoglobin (HbA1c) levels, blood clotting using International Normalized Ratio (INR), creatinine per milliliter (Cr/ml), and random blood sugar (RBG).

Patients in the control group were treated with 180µg of pegylated IFN (Pegasys-Roche) subcutaneously weekly for three months. In addition, they were given ribavirin according to their body weight (1200 mg for those over 75 kg and 1000 mg for those under 75 kg). The Biobran group was treated with Biobran, at a dose of 1g per day, allocated in packets, taken orally with meals for the three months duration of the study. Biobran is a denatured hemicellulose that is obtained by reacting rice bran hemicellulose with multiple carbohydrate hydrolyzing enzymes from Shiitake mushrooms. It is a polysaccharide that contains ß-1, 3-glucans, and activated hemicellulose. Biobran was kindly provided by Daiwa Pharmaceuticals Co. Ltd., Tokyo, Japan.

The patients were divided randomly into two groups: the Biobran group and the PEG interferon plus ribavirin (control) group . Prior to treatment, clinical characteristics were determined for the patients in each group. The clinical characteristics of the HCV patients were investigated for hepatitis C, alpha-fetoprotein (AFP) levels, total leucocyte count (TLC), Platelet (PLT) count, Hemoglobin (Hb) levels, triglyceride (TG) levels, glycated hemoglobin (HbA1c) levels, blood clotting using International Normalized Ratio (INR), creatinine per milliliter (Cr/ml), and random blood sugar (RBG).

Viral load levels, toxicity, liver enzymes, and γ-interferon (IFN-γ) levels were examined before and three months after treatment. Viral load was examined by quantitative polymerase chain reaction (PCR) test using COBAS® TaqMan® Analyzer (Roche Corporation). IFN-γ, AFP, ALT, and AST levels were analyzed using specific Elisa Kits, which were performed by Spectrum Chemical Manufacturing Corporation, Gardena, CA, USA, and toxicity was assessed by a questionnaire, physician observation, and laboratory results.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: June 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 65 Years

Eligibility

Inclusion Criteria:

• Patients diagnosed with chronic HCV infection and chronic active liver diseases.

Exclusion Criteria:

• Patients diagnosed with chronic HBV , HIV infection , autoimmune disorders , any heart diseases , any kidney diseases or any blood disease , any neoplastic disorders.

• Pregnant or lactating ladies , and drug abusers will be excluded.

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis C
• Hepatitis C, Chronic

Intervention

Drug:
• pegylated IFN
Patients are treated with 180µg of pegylated IFN (Pegasys-Roche) subcutaneously weekly for three months.

Dietary Supplement:
• Biobran
Biobran, at a dose of 1g per day, allocated in packets, taken orally with meals for the three months duration of the study. Biobran is a denatured hemicellulose that is obtained by reacting rice bran hemicellulose with multiple carbohydrate hydrolyzing enzymes from Shiitake mushrooms. It is a polysaccharide that contains ß-1, 3-glucans, and activated hemicellulose. Biobran was kindly provided by Daiwa Pharmaceuticals Co. Ltd., Tokyo, Japan.

Drug:
• Ribavirin
Ribavirin is prescribed according to patients body weight (1200 mg for those over 75 kg and 1000 mg for those under 75 kg).

Locations

Country	Name	City	State
n/a

Sponsors (3)

Lead Sponsor	Collaborator
Cairo University	Daiwa Pharmaceutical Corporation Co, Ltd, Tokyo 154-0024 Japan, University of California, Los Angeles

References & Publications (28)

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Cholujova D, Jakubikova J, Sedlak J. BioBran-augmented maturation of human monocyte-derived dendritic cells. Neoplasma. 2009;56(2):89-95. — View Citation

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Ghoneum M, Abedi S. Enhancement of natural killer cell activity of aged mice by modified arabinoxylan rice bran (MGN-3/Biobran). J Pharm Pharmacol. 2004 Dec;56(12):1581-8. — View Citation

Ghoneum M, Agrawal S. Activation of human monocyte-derived dendritic cells in vitro by the biological response modifier arabinoxylan rice bran (MGN-3/Biobran). Int J Immunopathol Pharmacol. 2011 Oct-Dec;24(4):941-8. — View Citation

Ghoneum M, Agrawal S. Mgn-3/biobran enhances generation of cytotoxic CD8+ T cells via upregulation of dec-205 expression on dendritic cells. Int J Immunopathol Pharmacol. 2014 Oct-Dec;27(4):523-30. — View Citation

Ghoneum M, Badr El-Din NK, Abdel Fattah SM, Tolentino L. Arabinoxylan rice bran (MGN-3/Biobran) provides protection against whole-body ?-irradiation in mice via restoration of hematopoietic tissues. J Radiat Res. 2013 May;54(3):419-29. doi: 10.1093/jrr/rrs119. Epub 2013 Jan 3. — View Citation

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Levent G, Ali A, Ahmet A, Polat EC, Aytaç C, Ayse E, Ahmet S. Oxidative stress and antioxidant defense in patients with chronic hepatitis C patients before and after pegylated interferon alfa-2b plus ribavirin therapy. J Transl Med. 2006 Jun 20;4:25. — View Citation

Noaman E, Badr El-Din NK, Bibars MA, Abou Mossallam AA, Ghoneum M. Antioxidant potential by arabinoxylan rice bran, MGN-3/biobran, represents a mechanism for its oncostatic effect against murine solid Ehrlich carcinoma. Cancer Lett. 2008 Sep 18;268(2):348-59. doi: 10.1016/j.canlet.2008.04.012. Epub 2008 Jun 12. — View Citation

Park Y, Pham TX, Lee J. Lipopolysaccharide represses the expression of ATP-binding cassette transporter G1 and scavenger receptor class B, type I in murine macrophages. Inflamm Res. 2012 May;61(5):465-72. doi: 10.1007/s00011-011-0433-3. Epub 2012 Jan 13. — View Citation

Pérez-Martínez A, Valentín J, Fernández L, Hernández-Jiménez E, López-Collazo E, Zerbes P, Schwörer E, Nuñéz F, Martín IG, Sallis H, Díaz MÁ, Handgretinger R, Pfeiffer MM. Arabinoxylan rice bran (MGN-3/Biobran) enhances natural killer cell-mediated cytotoxicity against neuroblastoma in vitro and in vivo. Cytotherapy. 2015 May;17(5):601-12. doi: 10.1016/j.jcyt.2014.11.001. Epub 2014 Dec 23. — View Citation

Rice CM. New insights into HCV replication: potential antiviral targets. Top Antivir Med. 2011 Aug-Sep;19(3):117-20. Review. — View Citation

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Sreenarasimhaiah J, Jaramillo A, Crippin J, Lisker-Melman M, Chapman WC, Mohanakumar T. Concomitant augmentation of type 1 CD4+ and CD8+ T-cell responses during successful interferon-alpha and ribavirin treatment for chronic hepatitis C virus infection. Hum Immunol. 2003 May;64(5):497-504. — View Citation

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University of Washington/Seattle STD/HIV Prevention Training Center. Hepatitis Web Study. 2013. Available at: http://www.cdc.gov/hepatitis/Resources/Professionals/PDFs/ABCTable.pdf. Accessed 29 November 2015.

* Note: There are 28 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Effect of BioBran on the viraemia levels in chronic HCV infected patients		3-month post treatment	Yes