Clinical trial NCT04646980: Biobran/MGN-3 Increases Innate Resistance and Reduces the Incidence of Influenza-like Illnesses
Official title: Dietary Supplementation With Biobran/MGN-3 Increases Innate Resistance Against Viral Infections That Cause Influenza-like Illnesses in Elderly Subjects: a Randomized, Double-blind, Placebo-controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Influenza-like Illness
Keywords: Biobran/MGN-3
Old adults
influenza-like illness
NK cells activity
Degranulation assay
RIG-1, MDA5, ISG15, MX1
Lead sponsor: Zagazig University
Sponsor class: OTHER_GOV
Collaborators: name: Charles Drew University of Medicine and Science
name: University of California, Irvine
name: Daiwa Pharmaceutical Corporation Co, Ltd, Tokyo 154-0024 Japan
First posted: 2020-11-30
Enrollment: 80
Sex: ALL
Minimum age (years): 56
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized double-blind placebo-controlled
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: ILI incidence rate
timeFrame: 12 weeks
measure: ILI incidence density
timeFrame: 3600 Person-days
measure: NK cell activity
timeFrame: 12 weeks
measure: RIG-1, MDA5, ISG15, MX1 expression
timeFrame: 72 hours
Secondary outcomes:
measure: Natural killer T-cells (NKT) cell activity
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Zagazig
country: Egypt
facility: Department of Community Medicine and Public Health, Faculty of Medicine, Zagazig University
state: Sharkia
Study officials:
affiliation: Department of Community Medicine and Public Health, Faculty of Medicine, Zagazig University
name: Ahmed F Elsaid, MD/PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.