Immunologic Deficiency Syndromes
Conditions
Keywords
Betaglucan, immune modulation, immunoparalysis, immune suppression
Brief summary
The purpose of this study is to test wether orally administered Beta-glucan has systemic effects in humans.
Detailed description
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. However, although Beta-glucans are widely used as a health food supplement, their immunomodulatory effects after administration in humans have not yet been determined.
Interventions
DIETARY_SUPPLEMENTBeta-glucan (Glucan #300®)
Sponsors
Radboud University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 36 Years
Healthy volunteers
Yes
Inclusion criteria
* Written informed consent * Age ≥18 * Healthy males
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 outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tumor Necrosis Factor (TNF)-α Secretion by ex Vivo Lipopolysaccharide (LPS)-Stimulated Peripheral Blood Mononuclear Cells (PBMCs) | up to 21 days | 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 |
Secondary
| Measure | Time frame |
|---|---|
| • the Absorbance of Orally Administered Beta-glucan Into the Blood Compartment, Measured by ELISA | Days 0, 6, 21 |
| • Transcriptional Pathways (by Use of Microarrays) With Focus on Inflammatory Pathways. | Days 0, 6, 21 |
| • Production of Other Cytokines (TNF-α, Interleukin (IL)-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, Staph Aureus) | days 0, 6, 21 |
| • the Leukocyte Capacity to Phagocytose and Kill the Fungal Pathogen Candida Albicans (Antifungal Activity). | Days 0, 6, 21 |
| the Composition of Faecal Microbiota | Days 0, 6, 21 |
| • Changes in Phenotype and Gene Expression Caused by Mechanisms Other Than Changes in the Underlying DNA Sequence (Epigenetic Modifications) | Days 0, 6, 21 |
Countries
Netherlands
Participant flow
Recruitment details
Recruitment took place from April until May 2013 in the Radboud University Medical Centre Nijmegen.
Pre-assignment details
Exclusion of subjects was based on pre-defined exclusion criteria or the unability of subjects to comply with the study time schedule.
Participants by arm
| Arm | Count |
|---|---|
| Beta-glucan Commercial available Beta-glucan derived from bakers yeast (S. Cerevisiae): Glucan #300® produced by Transferpoint, Columbia, United States. 2 capsules of 500mg Glucan #300®, daily, for seven days.
Beta-glucan (Glucan #300®) | 10 |
| Control Group No intervention | 5 |
| Total | 15 |
Baseline characteristics
| Characteristic | Beta-glucan | Control Group | Total |
|---|---|---|---|
| Age, Continuous | 20 years | 20 years | 20 years |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 10 Participants | 5 Participants | 15 Participants |
| TNF-α Secretion by ex Vivo LPS-Stimulated Peripheral Blood mononuclear cells | 691 pg/ml | 749 pg/ml | 720 pg/ml |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 10 | 0 / 5 |
| serious Total, serious adverse events | 0 / 10 | 0 / 5 |
Outcome results
Primary
Tumor Necrosis Factor (TNF)-α Secretion by ex Vivo Lipopolysaccharide (LPS)-Stimulated Peripheral Blood Mononuclear Cells (PBMCs)
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
Time frame: up to 21 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Beta-glucan | Tumor Necrosis Factor (TNF)-α Secretion by ex Vivo Lipopolysaccharide (LPS)-Stimulated Peripheral Blood Mononuclear Cells (PBMCs) | 691 pg/ml |
| Control Group | Tumor Necrosis Factor (TNF)-α Secretion by ex Vivo Lipopolysaccharide (LPS)-Stimulated Peripheral Blood Mononuclear Cells (PBMCs) | 749 pg/ml |
Secondary
• Changes in Phenotype and Gene Expression Caused by Mechanisms Other Than Changes in the Underlying DNA Sequence (Epigenetic Modifications)
Time frame: Days 0, 6, 21
Secondary
• Production of Other Cytokines (TNF-α, Interleukin (IL)-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, Staph Aureus)
Time frame: days 0, 6, 21
Secondary
• the Absorbance of Orally Administered Beta-glucan Into the Blood Compartment, Measured by ELISA
Time frame: Days 0, 6, 21
Secondary
the Composition of Faecal Microbiota
Time frame: Days 0, 6, 21
Secondary
• the Leukocyte Capacity to Phagocytose and Kill the Fungal Pathogen Candida Albicans (Antifungal Activity).
Time frame: Days 0, 6, 21
Secondary
• Transcriptional Pathways (by Use of Microarrays) With Focus on Inflammatory Pathways.
Time frame: Days 0, 6, 21