Biobran/MGN-3 Increases Innate Resistance and Reduces the Incidence of Influenza-like Illnesses

NCT ID: NCT04646980

Last Updated: 2020-11-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-11-28
• Study Completion Date: 2019-02-28

Brief Summary

Influenza is a seasonally-epidemic viral infection causing 3-5 million severe illnesses and up to approximately 500,000 annual deaths around the world. Influenza-like illnesses (ILI) is a simple constellation of symptoms and signs that was introduced to capture influenza cases in surveillance system. The elderly are more susceptible to cancers and viral infections including influenza infection and complications that was attributed to the phenomenon of immunosenescence or age-associated decline of immune system activity. Biobran/MGN3 is a natural nutritional supplement that was shown to exhibit potent immunomodulator effect such as enhancement of natural killer cell (NKC) activity and up-regulating the production of cytokines such as tumor necrosis factor-α (TNF- α), interferon-gamma (IFN-γ) and -lambda (IFN-λ). The protective effect of Biobran/MGN-3 against viral infection such hepatitis C virus (HCV) and human immunodeficiency virus (HIV) as well as several cancer types has been previously reported in experimental animal models and humans. The objective of the current study was to investigate the effect of Biobran/MGN-3 on some innate immune system components and the incidence of ILI in the older adult population. The studied innate immune system included NKC activity and the expressions of intracellular viral nucleic acid sensors such as retinoic acid-inducible gene 1 (RIG-1), melanoma differentiation-associated protein 5 (MDA5) and some of their downstream signals such as ISG15 and MX1.

Detailed Description

The current study investigated the effect of oral supplementation with Biobran/MGN-3, 500 mg every day for 3 months, on several components of innate immune system and the incidence rate of influenza-like illnesses (ILI) in older adults population. The study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki and was approval by Institutional Review Board (IRB) at the Faculty of Medicine, Zagazig University, Egypt. Zagazig University Hospitals serves over 1 million residents in Zagazig district and neighboring towns.

The study spanned the time period from November 2018 till the end of February 2019, a period with known peak incidence of ILI attacks. Subjects of ≥ 56 years were recruited from the visitors of outpatient clinics at Zagazig University Hospitals. The age of ≥ 56 years was used by the WHO to define old age in African nations. In addition, this age is close to public service retirement in Egyptian society, which is associated with significant social, mental, and psychological stress and therefore could be associated with significant decline in NK cell activity. Only local residents of Zagazig district were recruited to the study so as to reduce the dropout rate.

Originally 90 subjects, both males and females, were approached but only 80 subjects, 40 males and 40 females, continued the study. Ten of the recruits refused to participate when they realized that the sachets were only labeled with the manufacture symbols without printed names, which was used to ensure double-blinding. Informed consents were obtained from all participants and their right to unconditionally withdraw from the study at any time were made clear to them.

Males and females were randomly assigned into two groups (n=40/group) that received either placebo or Biobran/MGN-3 (500 mg/day for 3 months). Both the health care giver and the participants were blinded to the ingested supplement. Participants' health was monitored via weekly home visits and they were instructed to report any complaints or side effects by phone to the health care giver.

Diagnosis of ILI was made by documenting the incidence of acute respiratory illness with a measured temperature of ≥ 38 °C with cough (3). After diagnosis, the subject was helped to follow the proper health management plan by the health care giver. During the study, all participants were required not to take any vitamins or medications during the study without consultation.

The effect of Biobran/MGN-3 on liver, kidney, and hematological parameters were monitored. Liver functions were monitored using alanine aminotransferase (ALT/SGPT) and aspartate aminotransferase (AST/SGOT), whereas kidney function was monitored using serum uric acid. The assessed hematological parameters included red blood cell count (RBC), hematocrit value (HCT), hemoglobin (Hb), mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV), and total and differential (WBC).

NKC activity was measured using the well documented degranulation assay. The viral nucleic acid receptors, RIG-1 and MDA5, and their downstream target, ISG15 and MX1, were assessed using flowcytometry in BEAS-2B cells.

Conditions

Influenza-like Illness

Keywords

Biobran/MGN-3; Old adults; influenza-like illness; NK cells activity; Degranulation assay; RIG-1, MDA5, ISG15, MX1

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Biobran/MGN-3

This arm consisted from 20 males and 20 females. Biobran/MGN-3 was orally supplemented at dose of 500 mg per day for 3 months (end of November 2018- end of February 2019).

Group Type: EXPERIMENTAL

Biobran/MGN-3

Intervention Type: DIETARY_SUPPLEMENT

Biobran/MGN3 is defined by the Medicines and Healthcare products Regulatory Agency (MHRA) as a food supplement. Biobran/MGN3 is manufactured by hydrolyzing rice bran with the enzymatic extract of medicinal Shiitake mushrooms. Enzyme hydrolysis of rice bran produces arabinoxylane, a hemi-cellulose compound, which constitutes the active ingredient of biobran/MGN3.

Placebo

This arm consisted from 20 males and 20 females. Placebo, with the same appearance and taste, was orally supplemented at dose of 500 mg per day for 3 months (end of November 2018- end of February 2019).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Placebo, with same appearance and taste as Biobran/MGN-3, was given to control subjects at a dose of 500 mg everyday for 3 months

Interventions

Biobran/MGN-3

Biobran/MGN3 is defined by the Medicines and Healthcare products Regulatory Agency (MHRA) as a food supplement. Biobran/MGN3 is manufactured by hydrolyzing rice bran with the enzymatic extract of medicinal Shiitake mushrooms. Enzyme hydrolysis of rice bran produces arabinoxylane, a hemi-cellulose compound, which constitutes the active ingredient of biobran/MGN3.

Intervention Type: DIETARY_SUPPLEMENT

Placebo

Placebo, with same appearance and taste as Biobran/MGN-3, was given to control subjects at a dose of 500 mg everyday for 3 months

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Ages of 56+ years
• Both sexes will be included.
• Local residents of Zagazig district
• Willing to participate in the study and give a written consent.

Exclusion Criteria

• Subjects who took influenza vaccine, cortisone, or any other immunosuppressive agents such as radiation or chemotherapy.
• Diagnosed with infections or malignancies
• Presence of auto-immune disorders
• Marked portal hypertension, pancytopenia, renal, or kidney failure
• Presence of major psychological insult or under medication for psychological insult

• Minimum Eligible Age: 56 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Charles Drew University of Medicine and Science

OTHER

Sponsor Role: collaborator

University of California, Irvine

OTHER

Sponsor Role: collaborator

Daiwa Pharmaceutical Corporation Co, Ltd, Tokyo 154-0024 Japan

UNKNOWN

Sponsor Role: collaborator

Zagazig University

OTHER_GOV

Sponsor Role: lead

Responsible Party

Ahmed Farouk Elsaid

Assistant Professor of Community Medicine and Public Health

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ahmed F Elsaid, MD/PhD

Role: PRINCIPAL_INVESTIGATOR

Department of Community Medicine and Public Health, Faculty of Medicine, Zagazig University

Locations

Department of Community Medicine and Public Health, Faculty of Medicine, Zagazig University

Zagazig, Sharqia Province, Egypt

Countries

Egypt

References

Elsaid AF, Shaheen M, Ghoneum M. Biobran/MGN-3, an arabinoxylan rice bran, enhances NK cell activity in geriatric subjects: A randomized, double-blind, placebo-controlled clinical trial. Exp Ther Med. 2018 Mar;15(3):2313-2320. doi: 10.3892/etm.2018.5713. Epub 2018 Jan 8.

Reference Type: RESULT

PMID: 29456638 (View on PubMed)

Elsaid AF, Fahmi RM, Shaheen M, Ghoneum M. The enhancing effects of Biobran/MGN-3, an arabinoxylan rice bran, on healthy old adults' health-related quality of life: a randomized, double-blind, placebo-controlled clinical trial. Qual Life Res. 2020 Feb;29(2):357-367. doi: 10.1007/s11136-019-02286-7. Epub 2019 Sep 5.

Reference Type: RESULT

PMID: 31489525 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

4034-12-6-2018

Identifier Type: -

Identifier Source: org_study_id