The primary objective of the study is to evaluate the systemic effects of orally administered Beta-glucan on innate immune responses of leukocytes. The effects of Beta-glucan will be determined by measuring the ex-vivo responsiveness of leukocytes…
ID
Source
Brief title
Condition
- Immune disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome measure is the TNF-α secretion by ex vivo LPS-stimulated
peripheral blood mononuclear cells (PBMCs).
Secondary outcome
Secondary Objective(s): There are 6 secondary objectives:
1. To determine the production of other cytokines (TNF-, αIL-6, IL-10, IL-1β,
IL-17, IL-22, Interferon (IFN)-γ) by leukocytes ex vivo stimulated with various
stimuli (including LPS, Pam3Cys, Mycobacterium tuberculosis, Poly(I:C), Candida
albicans, staphylococcus aureus).
2. To determine the absorbance of orally administered Beta-glucan into the
blood compartment, measured by ELISA.
3. To determine the effects of Beta-glucan on changes in phenotype and gene
expression caused by mechanisms other than changes in the underlying DNA
sequence (epigenetic modifications).
4. To determine the effects of Beta-glucan on transcriptional pathways (by use
of microarrays) with focus on inflammatory pathways.
5. To determine the effects of Beta-glucan on the leukocyte capacity to
phagocytose and kill the fungal pathogen Candida albicans.
6. To determine the effects of Beta-glucan on faecal microbiota
Background summary
For centuries mankind has tried to improve their defense mechanisms against
invading pathogens. The innate immunity is the first line of defense after the
body*s mechanical barriers. In many pathological situations that occur
naturally (for example sepsis) or iatrogenic (for example chemotherapy),
enhancement of the immune response is desirable. However, immune stimulating
therapies are scarce, expensive, and often have undesirable side-effects. The
immunostimulatory properties of mushrooms have been recognized for centuries,
and *medicinal* mushrooms are still widely used in alternative medicine all
over the world. Although a number of fungal components have been implicated in
these properties, Beta-glucans have attracted the most attention [1]. Numerous
in vitro and animal studies have demonstrated immunomodulatory and anticancer
effects of Beta-glucans. Moreover, recent molecular immunological studies have
elucidated the immunological mechanisms behind recognition of glucans by immune
cells and subsequent alterations of cellular responses [2]. However, although
Beta-glucans are widely used as a health food supplement, their
immunomodulatory effects after administration in humans have not yet been
determined.
Study proposal
In the present application we propose to conduct a pilot study to investigate
the effects of a commonly available and orally administered Beta-glucan on the
innate immune response of leukocytes in humans.
Study objective
The primary objective of the study is to evaluate the systemic effects of
orally administered Beta-glucan on innate immune responses of leukocytes. The
effects of Beta-glucan will be determined by measuring the ex-vivo
responsiveness of leukocytes to various inflammatory stimuli as a surrogate
marker of the antimicrobial response, and the pathogen phagocytosis and killing
capacity of leukocytes.
Study design
An unblinded, intervention pilot-study in healthy human volunteers. 15 Healthy
volunteers who meet all inclusion criteria, none of the exclusion criteria and
have given informed consent to participate in the study will be randomized to
the Beta-glucan or the control group. The subjects in the Beta-glucan group
will take Beta-glucan 1000 mg daily for 7 days, the subjects in the control
group won*t have to take Beta-glucan but will otherwise follow the same
timecourse as the Beta-glucan treated subjects. Before, and 3, 6, and 24 hours
after the first Beta-glucan ingestion (day 0), before, and 3 and 6 hours after
the 7th ingestion of Beta-glucan (day 6), and on day 21 subjects have to come
to the research room of the intensive care research unit for blood sampling.
Before the first intake of beta-glucan subjects have to hand in 2 faecal
samples collected within 24 hours prior to Beta-glucan intake, and one faecal
sample collected at days 6 and 21.
Intervention
Beta-glucan that is commonly available as a health food supplement derived from
bakers yeast (S. cerevisiae) and that has been used in vivo in mice with strong
immune modulating properties and no observed toxicity [39, 40] (Glucan #300®,
produced by transferpoint, Columbia, United States). Dosage is based on the
dosage recommended by the manufacturer.
Study burden and risks
Beta-glucans are commonly available as health food supplements and are
considered safe and non-toxic, with the classification of *GRAS* (Generally
recognized as safe) by the FDA as a dietary food additive supplement, and by
the Dutch Medicinal Evaluation Board (MEB) . Furthermore, in total 560 ml blood
will be drawn which is also not expected to result in side effects. Therefore,
no (severe or non-severe) side-effects are anticipated.
Geert Grooteplein-Zuid 10
Nijmegen 6525 GA
NL
Geert Grooteplein-Zuid 10
Nijmegen 6525 GA
NL
Listed location countries
Age
Inclusion criteria
- Written informed consent;
- Age >=18;
- Healthy male;
Exclusion criteria
- Subjects with a history of allergy or intolerance to Beta-glucan;
- Use of any medication;
- Participation in a drug trial or donation of blood 3 months prior to Beta-glucan administration;
- Use of antibiotics, norit, laxatives (up till 6 months prior to inclusion), cholestyramine, acid burn inhibitors or immune suppressive agents (up till 3 months prior to inclusion), and pre- and probiotics (up till 1 month prior to inclusion).
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2012-003154-91-NL |
| CCMO | NL41367.091.12 |