Healthy
Conditions
Keywords
probiotic, allergy, immune
Brief summary
In this randomized, double-blind, placebo-controlled study, participants with seasonal allergies will receive a daily probiotic or placebo for 8 weeks. Questionnaires will assess health-related quality of life, stress, physical activity, gastrointestinal symptoms, adverse events, and compliance. In a subset of subjects, stool and blood samples will be collected at baseline and at week 6 of the intervention (estimated to be peak allergy season) to characterize microbial communities and immune function.
Interventions
DIETARY_SUPPLEMENTProbiotic mixture
A 350 mg capsule containing a mixture of Lactobacillus gasseri, Bifidobacterium bifidum, and Bifidobacterium longum (1.5 billion cells per capsule prior to expiration) will be taken twice daily for 8 weeks by subjects in the group receiving this supplement (group is unknown, double-blinded). Inactive ingredients include gelatin, potato starch, and silica.
DIETARY_SUPPLEMENTPlacebo
Placebo will be taken as a capsule twice daily for 8 weeks by subjects in the group receiving this supplement (group is unknown, double-blinded). Supplement contains 348.25 mg of potato starch.
Sponsors
Wakunaga Pharmaceutical Co., Ltd.
University of Florida
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
Subjects will be included if they: * are 18 to 60 years of age (inclusive). * receive a score of 2 or greater on the Mini Rhinoconjunctivitis Quality of Life Questionnaire. * are willing and able to complete the Informed Consent Form in English. * are available for 8 consecutive weeks to participate in this study. * be willing and able to complete online daily and weekly questionnaires regarding general wellness, bowel function, quality of life, gastrointestinal symptoms, and physical activity. * are willing and able to maintain their regular level of physical activity and diet for the 8-week study. * are able to take the study supplement without the aid of another person. * are willing to discontinue consumption of fermented foods or probiotics (e.g., yogurts with live, active cultures or supplements), or immune-enhancing supplements (e.g., Echinacea or fish oil). * are willing to provide 2 blood and 2 stool samples (subgroup only).
Exclusion criteria
Subjects will be excluded if they: * do not meet any of the above criteria. * use allergy medications, including nasal sprays, 5 or more days per week. * receive allergy shots. * are currently pregnant or attempting to get pregnant. * are currently taking any systemic corticosteroids, androgens (such as testosterone), or large doses of anti-inflammatory drugs (i.e., aspirin in doses \>600 mg/d) on a regular basis. * are currently being treated for or have any of the following physician-diagnosed diseases or conditions: HIV/AIDS; immune modulating diseases (autoimmune disease, hepatitis, cancer, etc.); kidney disease; pancreatitis; pulmonary disease; hepatic or biliary disease; or gastrointestinal diseases/conditions such as diverticulitis, ulcerative colitis, Crohn's disease, Celiac disease, short bowel disease, ileostomy, or colostomy, but not including GERD; or have a central venous catheter. * have received chemotherapy or other immune suppressing therapy within the last year.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Health-related Quality of Life Score From Baseline to the Peak Week of Allergy Season for Probiotic Versus Placebo, as Measured by MiniRQLQ | up to 8 weeks from date of randomization | MiniRQLQ, global score (0=not troubled, 6=extremely troubled; an average of the 14 questions; includes all domains) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Regulatory T Cells (Tregs) | baseline and week 6 | Regulatory T cells (Tregs) as a percentage of CD4+ T cells, quantified via flow cytometry |
| Serum Total Immunoglobulin E (IgE) | baseline and week 6 | Serum total immunoglobulin E (IgE) was quantified via ELISA |
| Constipation Symptom Score, Measured by Gastrointestinal Symptom Response Scale (GSRS) Questionnaire | weeks 0, 1, 2, 3, 4, 5, 6, 7 | Symptoms included in this score are constipation, hard stools, and feeling of incomplete evacuation reported on a weekly Gastrointestinal Symptom Response Scale (GSRS) questionnaire. Questionnaire asks participants about the previous seven days. Scores range from 1 (no discomfort) to 7 (very severe discomfort); lower scores are more desirable. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from the Gainesville, FL area, including the University of Florida campus. Recruiting began in January of 2015 and took place in facilities within the Food Science and Human Nutrition Department at the University of Florida. Participants were enrolled from 1-20-15 to 3-12-15.
Pre-assignment details
Before randomization, participants provided anthropometric measurements and demographic information. Out of the 224 participants who consented to participate, only 173 remained at randomization due to the participants no longer being interested or not coming to their study visits to be randomized.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo was to be taken as a capsule twice daily for 8 weeks by subjects in the group receiving this supplement (group was unknown, double-blinded). Supplement contains 348.25 mg of potato starch. | 87 |
| Probiotic Mixture A 350 mg capsule containing a commercially available probiotic mixture of Lactobacillus gasseri, Bifidobacterium bifidum, and Bifidobacterium longum (1.5 billion cells per capsule prior to expiration) was to be taken as a capsule twice daily for 8 weeks by subjects in the group receiving this supplement (group was unknown, double-blinded). Inactive ingredients included gelatin, potato starch, and silica. | 86 |
| Total | 173 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | Placebo | Probiotic Mixture | Total |
|---|---|---|---|
| Age, Continuous | 27.6 years STANDARD_DEVIATION 13.1 | 26.0 years STANDARD_DEVIATION 10.8 | 26.8 years STANDARD_DEVIATION 12 |
| Sex: Female, Male Female | 65 Participants | 54 Participants | 119 Participants |
| Sex: Female, Male Male | 22 Participants | 32 Participants | 54 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 87 | 0 / 86 |
| serious Total, serious adverse events | 0 / 87 | 0 / 86 |
Outcome results
Primary
Change in Health-related Quality of Life Score From Baseline to the Peak Week of Allergy Season for Probiotic Versus Placebo, as Measured by MiniRQLQ
MiniRQLQ, global score (0=not troubled, 6=extremely troubled; an average of the 14 questions; includes all domains)
Time frame: up to 8 weeks from date of randomization
Population: Because this was an intent-to-treat study, all data from all randomized participants was considered for analysis. No imputation was done, so missing values excluded a participant from the analysis. While data from a participant may be missing, they were considered to have completed the study if they completed all study visits.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Health-related Quality of Life Score From Baseline to the Peak Week of Allergy Season for Probiotic Versus Placebo, as Measured by MiniRQLQ | -0.1946 units on a scale | Standard Error 0.1386 |
| Probiotic Mixture | Change in Health-related Quality of Life Score From Baseline to the Peak Week of Allergy Season for Probiotic Versus Placebo, as Measured by MiniRQLQ | -0.6772 units on a scale | Standard Error 0.1302 |
Secondary
Constipation Symptom Score, Measured by Gastrointestinal Symptom Response Scale (GSRS) Questionnaire
Symptoms included in this score are constipation, hard stools, and feeling of incomplete evacuation reported on a weekly Gastrointestinal Symptom Response Scale (GSRS) questionnaire. Questionnaire asks participants about the previous seven days. Scores range from 1 (no discomfort) to 7 (very severe discomfort); lower scores are more desirable.
Time frame: weeks 0, 1, 2, 3, 4, 5, 6, 7
Population: Since this outcome had more than two time points, and since all randomized participants provided some weeks of survey data, all participants were included in the analysis (even those that were lost to follow up). The number of values (and thus the number analyzed) by week is also shown.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Constipation Symptom Score, Measured by Gastrointestinal Symptom Response Scale (GSRS) Questionnaire | Week 0 | 1.57 units on a scale | Standard Error 0.09 |
| Placebo | Constipation Symptom Score, Measured by Gastrointestinal Symptom Response Scale (GSRS) Questionnaire | Week 1 | 1.51 units on a scale | Standard Error 0.08 |
| Placebo | Constipation Symptom Score, Measured by Gastrointestinal Symptom Response Scale (GSRS) Questionnaire | Week 2 | 1.59 units on a scale | Standard Error 0.09 |
| Placebo | Constipation Symptom Score, Measured by Gastrointestinal Symptom Response Scale (GSRS) Questionnaire | Week 3 | 1.68 units on a scale | Standard Error 0.09 |
| Placebo | Constipation Symptom Score, Measured by Gastrointestinal Symptom Response Scale (GSRS) Questionnaire | Week 4 | 1.73 units on a scale | Standard Error 0.11 |
| Placebo | Constipation Symptom Score, Measured by Gastrointestinal Symptom Response Scale (GSRS) Questionnaire | Week 5 | 1.61 units on a scale | Standard Error 0.08 |
| Placebo | Constipation Symptom Score, Measured by Gastrointestinal Symptom Response Scale (GSRS) Questionnaire | Week 6 | 1.60 units on a scale | Standard Error 0.08 |
| Placebo | Constipation Symptom Score, Measured by Gastrointestinal Symptom Response Scale (GSRS) Questionnaire | Week 7 | 1.65 units on a scale | Standard Error 0.08 |
| Probiotic Mixture | Constipation Symptom Score, Measured by Gastrointestinal Symptom Response Scale (GSRS) Questionnaire | Week 7 | 1.31 units on a scale | Standard Error 0.06 |
| Probiotic Mixture | Constipation Symptom Score, Measured by Gastrointestinal Symptom Response Scale (GSRS) Questionnaire | Week 0 | 1.51 units on a scale | Standard Error 0.08 |
| Probiotic Mixture | Constipation Symptom Score, Measured by Gastrointestinal Symptom Response Scale (GSRS) Questionnaire | Week 4 | 1.41 units on a scale | Standard Error 0.07 |
| Probiotic Mixture | Constipation Symptom Score, Measured by Gastrointestinal Symptom Response Scale (GSRS) Questionnaire | Week 1 | 1.49 units on a scale | Standard Error 0.08 |
| Probiotic Mixture | Constipation Symptom Score, Measured by Gastrointestinal Symptom Response Scale (GSRS) Questionnaire | Week 6 | 1.37 units on a scale | Standard Error 0.06 |
| Probiotic Mixture | Constipation Symptom Score, Measured by Gastrointestinal Symptom Response Scale (GSRS) Questionnaire | Week 2 | 1.53 units on a scale | Standard Error 0.08 |
| Probiotic Mixture | Constipation Symptom Score, Measured by Gastrointestinal Symptom Response Scale (GSRS) Questionnaire | Week 5 | 1.48 units on a scale | Standard Error 0.07 |
| Probiotic Mixture | Constipation Symptom Score, Measured by Gastrointestinal Symptom Response Scale (GSRS) Questionnaire | Week 3 | 1.42 units on a scale | Standard Error 0.07 |
Secondary
Regulatory T Cells (Tregs)
Regulatory T cells (Tregs) as a percentage of CD4+ T cells, quantified via flow cytometry
Time frame: baseline and week 6
Population: A subgroup of participants who completed the main study (questionnaire data only) also completed an additional portion of the study in which they provided blood and stool samples. Some samples could not be accurately measured for this outcome, so those samples were excluded from analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Regulatory T Cells (Tregs) | Week 6 | 4.7733 percentage of CD4+ T lymphocytes | Standard Error 0.2004 |
| Placebo | Regulatory T Cells (Tregs) | Baseline | 4.1931 percentage of CD4+ T lymphocytes | Standard Error 0.2427 |
| Probiotic Mixture | Regulatory T Cells (Tregs) | Baseline | 4.4146 percentage of CD4+ T lymphocytes | Standard Error 0.2533 |
| Probiotic Mixture | Regulatory T Cells (Tregs) | Week 6 | 4.8626 percentage of CD4+ T lymphocytes | Standard Error 0.2007 |
Secondary
Serum Total Immunoglobulin E (IgE)
Serum total immunoglobulin E (IgE) was quantified via ELISA
Time frame: baseline and week 6
Population: A subgroup of participants who completed the main study (questionnaire data only) also completed an additional portion of the study in which they provided blood and stool samples.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Serum Total Immunoglobulin E (IgE) | Baseline | 325.3243243 ng/mL | Standard Error 51.4187025 |
| Placebo | Serum Total Immunoglobulin E (IgE) | Week 6 | 352.6111111 ng/mL | Standard Error 56.561545 |
| Probiotic Mixture | Serum Total Immunoglobulin E (IgE) | Baseline | 781.0285714 ng/mL | Standard Error 103.2435603 |
| Probiotic Mixture | Serum Total Immunoglobulin E (IgE) | Week 6 | 843.3428571 ng/mL | Standard Error 107.3421604 |