Yeast-derived Beta-glucan Supplementation on Antibody Response Following Influenza Vaccination: A Randomized, Placebo-controlled Study (M-Unity)
Phase: PHASE2
Conditions: Healthy Aging
Sponsor: University of Florida

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Yeast-derived beta-glucan supplementation on antibody response following influenza 
vaccination: A randomized, placebo-controlled study (M-Unity). 
 
NCT05074303 
 
Date: 11-21-2023 
 
 

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Title: Yeast-derived beta-glucan supplementation on antibody response following influenza 
vaccination: A randomized, placebo-controlled study (M-Unity). 
 
Principal Investigator 
Wendy Dahl RD PhD  
Associate Professor 
Food Science and Human Nutrition Department UF/IFAS and Center for Nutritional Sciences 
359 FSHN Building Newell Drive 
Gainesville, FL 32611 USA 
e-mail: wdahl@ufl.edu 
Tel: 352-294-3707  
 
Research Sites  
FSHN Clinical Lab, Food Science and Human Nutrition Department 
Food Science and Human Nutrition Department UF/IFAS and Center for Nutritional Sciences 
359 FSHN Building Newell Drive 
Gainesville, FL 32611 USA 
 
Oak Hammock Retirement Community 
5100 SW 25th Blvd,  
Gainesville, FL 32608 
 
Village at Gainesville 
8000 NW 27th Boulevard 
Gainesville, FL 32606 
 
Clinical Research Center 
Clinical Translational Science Institute 
2004 Mowry Road, Gainesville, FL 32610 
 
Study Sponsor 
 
Danstar Ferment AG 
Poststrasse 30 
6300 Zug 
Switzerland 
 
Sponsor Contact: 
Thomas A. Tompkins, Ph.D. 
Health Ingredients Research & Innovation Director 
Lallemand Bio Ingredients 
6100 ave Royalmount 
Montreal, QC 
Canada H4P 2R2 
Tel: 514 944 3942 
Email: ttompkins@lallemand.com 

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Background 
Functional differences in the aging immune system has been studied in animal models and humans 
(Nikolich-Žugich 2014; Scholz et al. 2013). It has been proposed that these differences are due to 
immunosenescence, a term used to describe the decline in immune system function with older age. 
With aging, there is not only an increase in the severity of viral and bacterial infections but also a 
decrease in vaccine immunological responses, which often leads to a failure to induce long-term 
protective immunity (Crooke et al. 2019). Hence, there is a need of adjuvant nutritional therapies 
to improve the immunological response to vaccination. Beta-glucans have been shown to enhance 
the innate and adaptive immune responses in cell cultures, animal models, and humans (Harnack 
et al. 2009; Hetland and Sandven 2002; Lehne et al. 2006; Sandvik et al. 2007; Tsukada et al. 
2003; Yu et al. 2015). Thus, adults over the age of 50 years receiving the influenza vaccination 
may benefit in terms of their immunological response from supplementation with beta-glucans. 
Study Aims and Outcomes 
 
The primary aim of the study is to determine the effects of beta-glucan, a dietary fiber supplement 
isolated from baker’s yeast, on immune response to the influenza vaccine.  
 
Primary outcome 
 
• Change in immune response to the influenza vaccine after beta-glucan supplementation 
[Time Frame: 28 days (Baseline (day 1), pre-vaccine visit (~day 1), and study end (~day 
28)]; Influenza-specific antibodies (IgM, IgG influenza A and B). 
Secondary outcomes 
 
• Inflammatory cytokine profile (TNF-α, IL-1β, IL-6, IL-8, and IFN-γ) [Time Frame: 28 
days (Pre-vaccine visit, post-vaccine visit (~day 2-3) and study end)] 
• Self-reported incidence of influenza and COVID-19 (Note: Data of subjects reporting 
incidence of influenza or COVID-19 during the study will be excluded from the final 
analysis) [Time Frame: 28 days]  
• Number of subjects with fever during the study [Time Frame: 28 days] Body temperature 
(ºC) 
• Number of subjects with cold and flu symptoms [Time Frame: 28 days] Modified 
Jackson Criteria 
• Fatigue [Time Frame: 28 days (Days 1 – 28) 
Additional information collected 
 
• Demographic data 
• Adverse events  
• Vaccinations (including COVID-19 booster) received during the month prior to the study 
start and during the study period 
• Compliance 

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o Reported intake of the supplement.  
o Number of unconsumed supplements (returned) 
 
Study Participants 
 
This is a 2-arm placebo, controlled study. A total of 120 volunteers (60 in each arm) will be 
recruited for the study. Subjects who do not meet the inclusion criteria or who meet any of the 
exclusion criteria will not be eligible to participate. 
 
Sample Size Calculation  
 
This is a pilot study, and thus sample size is based on similar published studies.  
 
Inclusion criteria  
1. Adult volunteers ≥40 years of age.  
2. Planning to be vaccinated for influenza  
3. Have been immunized for COVID-19 (self-disclosure) 
4. Willing and able to provide written informed consent in English. 
5. Willing and able to comply with all the study-related procedures, including attending to 
study visits for blood draw, taking the influenza vaccine, intake of the study supplement, 
and completing study questionnaires. 
 
Exclusion Criteria 
1. Demonstrate an inability to comply with the study-related procedures. 
2. Have a history of a severe reaction or hypersensitivity following vaccination with 
influenza vaccine, vaccination with any other vaccine containing the same substances, or 
intake of the study product.  
3. Be on immune-suppressing treatment (e.g., steroids (last 30 days); cytotoxic drugs, 
medical surgery, or radiation therapy during the 6 months, previous to enrollment). 
4. Be concurrently participating in a clinical trial that, in the judgement of the investigator, 
would interfere with the evaluation of the study outcomes. 
Inclusion of Women and Minorities 
Both men and women and members of all races and ethnic groups are eligible for this trial. 
Recruitment 
Potential participants will be recruited through flyers and word of mouth at the University of 
Florida, Oak Hammock Retirement Community, the Village at Gainesville, and the Gainesville 
Senior Center. We may also distribute the flyer through the Food Science and Human Nutrition 
(FSHN) department's website and Facebook page and through FSHN department faculty and staff 
listservs and Oak Hammock listserv. In addition, we will recruit through flyers and word of mouth 
at Gainesville and area churches, senior centers, senior communities, and local gyms as well as 
place an ad in the Gainesville Sun newspaper. Individuals interested in participating will be given 
the option to attend informational meetings in which the study will be explained in more detail. 

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Pre-screening will occur via an in-person interview or telephone contact script. The study will be 
described to the potential study participant using the approved script and the inclusion/exclusion 
criteria will be read. Potential study participants will be directed to listen to the criteria, without 
directly answering (stating “yes” or “no”) after each criterion is read, and then decide whether they 
would like to continue with study procedures. If the potential participant is still interested in 
participating and still believes they may qualify, an appointment will be scheduled for consenting.   
Investigational Product (IP) 
 
Manufacturing and Storage 
The Investigational Products (beta-glucan and placebo) will be manufactured by Biotec 
Betaglucans (Lallemand inc., Tromsø, Norway) and provided to the study site, FSHN Clinical Lab, 
Food Science and Human Nutrition Department. The IP will be carefully stored at the study site 
in a lockable, limited access area, accessible only by study team personnel in compliance with 
pertinent regulations. Only authorized persons will have access to the IP. The IP should be stored 
3–10 °C. 
 
Beta-Glucan 
The product under study is beta-glucan at 500 mg/day (2 capsules per day). The group randomized 
to the beta-glucan intervention will receive sufficient IP to cover the entire length of the 
intervention period (28 days). 
Placebo 
The placebo product is cellulose, an inert dietary fiber, 500 mg/day (2 capsules per day). The 
product has a very similar appearance, texture and taste as the beta-glucan product and will have 
identical packaging. The group randomized to the placebo intervention will receive sufficient IP 
to cover the entire length of the intervention period (28 days). 
Direction of Use 
Participants will be instructed to consume the supplement (500 mg/d) for 28 days following the 
influenza vaccination.  
Study design 
This is a 6-week randomized, double-blind, placebo-controlled, 2-arm parallel study designed to 
evaluate the adjuvant effect of beta-glucan dietary supplementation during influenza vaccination. 
This study will have a 28-day intervention period.  
During the pre-screening by telephone or in-person, the study and inclusion and exclusion criteria 
will be explained. Any restrictions linked to the study will also be explained. Sufficient time will 
be allowed for the potential participants to decide whether or not they wish to participate in the 
clinical study. If the potential participant decides to participate, a screening appointment will be 
scheduled to sign the informed consent and to perform the first study activities.   

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During the screening appointment (by Zoom or in person), the inclusion and exclusion criteria will 
be reviewed without responses to the individual items, and if the participant believes they are 
qualified, the informed consent will be signed via RedCap or in person. Following informed 
consent, the inclusion and exclusion criteria will be reviewed again, this time with responses to 
each item and recorded. Each study participant will receive a unique identifier. Within 24-hr prior 
to Visit 1, links to the Qualtrics demographic form (age, sex, race, and ethnicity) will be sent to 
participants for completion. Alternatively, the participant will be given the option of completing 
the questionnaire in person during Visit 1. At Visit 1, a baseline blood draw will be performed, 
and the participants will be randomized to either the beta-glucan or placebo group and will be 
instructed about the daily consumption of the IP for 28 days. Participants will then receive an 
influenza vaccine.  Take-away breakfasts will be offered following blood draws. Participants will 
be requested to complete an online Qualtrics or paper-based daily questionnaire of compliance, 
and cold, and flu and fatigue symptoms throughout the 28-day study. 
A second blood draw within 24-48 hours following their influenza vaccination (Visit 2) will be 
taken. A final blood draw will be completed on day 28 (Visit 3 - study end). Adverse events, 
including any illnesses, will be queried. 
 
Randomization 
Participants will be randomized to either the beta-glucan or the placebo group in a 1:1 fashion. 
Randomization will be used in this study to avoid bias in the assignment of participants to 
intervention, to increase the likelihood that known and unknown participant attributes (e.g., 
demographics and baseline characteristics) are balanced across intervention groups, and to ensure 
the validity of statistical comparisons across intervention groups. 
Randomization will be done by a computer-generated code, sealed envelope method and 
completed by an individual not involved in the study. Each random allocation will be arranged to 
fit on a single sheet of white paper that indicated the study sequence, and which also had blank 
spaces for the participant’s study number, date, the number of IP provided to the participant, and 
the number of IP returned by the participant. These sheets will be placed in envelopes and sealed. 
Each envelope will have an envelope number printed on it. The study staff will unseal the 
envelopes and assign the participant to a study sequence. 
Blinding 
Prior to delivery to the study site, the beta-glucan and placebo will be coded by an unblinded 
personnel at Lallemand inc. who will have no direct contact with participants, and no involvement 
with study procedures. Blinding to intervention will be used to reduce bias during data collection 
and evaluation of outcomes.  
 
 
 

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Unblinding 
Unblinding should not occur except in the case of an emergency. In the event that a serious adverse 
event (SAE) occurs, for which the identity of the study supplement administered is necessary to 
manage the participant’s condition, the randomization code for that participant may be broken and 
the study supplements identified. 
All emergency code breaks must be reported to Lallemand inc. project manager within 24 hours. 
The time, date, reason and who broke the blind, must be documented in the source documents. 
Details of participants who are unblinded during the study will be included in the final report. 
The probiotic and placebo will be double coded, so in the event of an SAE and unblinding of one 
code, information about 75% of the subjects will remain blinded. 
Compliance 
Compliance and adverse events will be monitored in the daily questionnaire throughout the 
intervention phase. Compliance also will be assessed by counting the number of study supplements 
returned by the participant at the end of the intervention. Compliance is calculated by determining 
the number of study supplements consumed from start of study IP (V1) to end of study IP (V3) 
divided by the number expected to have been taken multiplied by 100 to obtain the percentage 
consumed. Participants found to have a compliance of <80% will be considered noncompliant. 
 
Data Analysis Plan  
 
Statistical consultation will be utilized for data analyses. Statistical methods will be consistent with 
the CONSORT 2010 Statement (including statistical methods used to compare groups for primary 
and secondary outcomes and methods for additional analyses, such as subgroup analyses and 
adjusted analyses). 
 
Data Management Plan 
 
Data about the intervention effects will be collected from the participants electronically and on 
paper. Data and files will be secured in locked filling cabinets and office space. Paper 
questionnaires will only include date and research study assigned participant number. Data that is 
originally captured as hardcopy/paper (e.g., demographics and vital signs) will be transcribed to 
encrypted electronic files.  
 
Following the completion of the study, identifiers will be removed from data to meet HIPAA de-
identification standards (According to the October 2002 Privacy Rule § 164.514.(b).2. the 
indicated information/will be removed from all study records). 
 
All software applications used in the collection of data will be properly validated following 
standard computer system validation that is compliant with all regulatory requirements.  
 
 

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Potential Discomforts and Risks 
 
Beta-glucan, a dietary fiber, poses no known risks. Beta-glucan, a fiber, poses no known risks. 
However, there are some potential discomforts and risks related to the study. Drawing blood from a 
vein may result in discomfort at the site of puncture; possible bruising and swelling around the 
puncture site; rarely an infection; and, uncommonly, faintness from the procedure. Some people may 
feel uncomfortable answering questions about incidence of influenza, cold and flu symptoms, mood 
and feelings, and fatigue symptoms. Some people may feel uncomfortable or have difficulties 
swallowing capsules. You can open the capsule and add to a food such as apple sauce if you prefer. 
There is a risk of possible loss of confidentiality.  
 
Informed consent forms given to all participants specify Dr. Dahl as the contact in the case of 
issues or questions arising during the study. In the case that a professional intervention is necessary 
due to an adverse effect on the study subjects, Dr. Dahl will contact the appropriate authority or 
organization pertinent to the circumstance of the event. Serious adverse events will be reported to 
the sponsor within 24 h of the PI being notified. In the event of a data safety breach, Dr. Dahl and 
the appropriate University of Florida personnel will contact participants to inform them of this 
breach, as well as notify the Institutional Review Board of the University of Florida. 
 
Potential Benefits 
 
It is possible that those participants randomized to the beta-glucan may respond with a greater 
antibody titer to the influenza vaccine.  
 
Conflict of Interest 
The investigator declares no conflict of interest.  
Compensation 
 
For participating and completing the study, participants will receive $25 per blood draw and $25 
per week for daily questionnaire completion for a total of $175. If a participant drops out during 
the study, compensation will be prorated at $25 per week and $25 per blood draw. Should a 
participant not complete the entirety of the study due to a withdrawal, disqualification, or any other 
reason, compensation will be based upon completing pre-determined benchmarks. In all cases, 
compensation will be provided at the end of the study.  
 
 
 

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